Amphotericin B-Loaded Bigel: Characterization and in vivo Antileishmanial Evaluation in BALB/c Mice Infected with Leishmania amazonensis - Rosilene Ribeiro de Sousa; Matheus Oliveira do Nascimento; Leandro Josuel da Costa Santos; Francisco Gesley de Sousa Abreu; André Luiz Pinheiro de Moura; Daniele Costa Lopes; Karla Germana dos Reis Bacelar; Rita de Cássia Vianna de Carvalho; Paulline Paiva Mendes de Souza Leal; Charllyton Luis Sena da Costa; Vitória de Cássia Coelho Rodrigues; Fernando Aécio de Amorim Carvalho; et al. (AAPS PharmSciTech, 2026)

Meloxicam Eluting 3D Printed 316L Stainless Steel Implants for Targeted Delivery in Bone Fixation Surgeries - Manjusha Annaji; Ishwor Poudel; Nur Mita; Chu Zhang; Humaira Yeasmin; Seungjong Lee; Peter Panizzi; Robert D. Arnold; Amal Kaddoumi; Nima Shamsaei; Byron Farnum; Oladiran Fasina; et al. (AAPS PharmSciTech, 2026)
Implant failures in orthopedic surgeries can occur due to inflammation, poor osteointegration, and biofilm formation. The local delivery of anti-inflammatory drugs is one of the potential solutions to address orthopedic implant failures caused by extensive inflammation, poor osteointegration, and biofilm formation. This study utilized a simple spray coating technique to deposit multilayer coatings of the anti-inflammatory drug meloxicam and PLGA on 3D printed 316L stainless steel implants. The implants were evaluated for their drug content, drug-polymer miscibility, static contact angle, corrosion resistance, in vitro release, cell adhesion, cell proliferation, and bacterial adhesion studies. The coatings aimed to improve osteointegration and reduce biofilm formation. The drug release studies demonstrated an initial burst release accompanied by sustained release for more than 30 days. The meloxicam-PLGA coated implants showed higher resistance to pitting corrosion, improved adhesion, and proliferation of human U2OS cells in comparison to uncoated implants. In addition, results from cell cytotoxicity studies confirmed that all the coatings are biocompatible and safe for in vivo application. The meloxicam-PLGA coated implants were also found to have significantly lower bacterial adhesion and biofilm formation compared to uncoated implants for both S. aureus ( p S. pseudintermedius ( p Graphical Abstract

ML-Driven Pharmaceutical Cocrystal Technology: Advances in Screening, Property Prediction and Applications - Qian Ye; Sheng Wang; Zhaoyang Zhang (AAPS PharmSciTech, 2026)

Vanillic Acid-Loaded Niosomes for Diabetic Wound Healing: Formulation, Optimization by Box–Behnken Design, and In Vivo Evaluation - Shervin Amirkhanloo; Reza Enayatifard; Jafar Akbari; Mohammad Seyedabadi; Majid Saeedi; Mohammad Ranaee (AAPS PharmSciTech, 2026)

Effect of Process and Formulation Variables on Quality, Stability, and Taste of Lamivudine Printlets Manufactured by Binder Jetting 3D Printing Method - Tahir Khuroo; Linh H. Maracchini; Ziyaur Rahman; Mansoor A. Khan (AAPS PharmSciTech, 2026)

Preclinical Toxicity and Pharmacokinetic Evaluation of Paclitaxel Nanodispersion - Ajay J. Khopade; Malay D. Shah; Bhushan S. Borole; Bharat Patel; Bharat Pateliya; Vinod Burade (AAPS PharmSciTech, 2025)

Improved Oral Bioavailability and Brain Distribution of Hesperidin via Cochleate Formulation: Statistical Optimization and Pharmacokinetic Study - Komaldeep Kaur; Yogesh A. Kulkarni; Sarika Wairkar (AAPS PharmSciTech, 2025)

Exploring the Co-delivery of Sorafenib and Venetoclax to Induce Ferroptosis and Apoptosis Mediated Cancer Cell Death using Surface Modified PLGA Nanoparticles - Dhruv Patel; Smriti Bhardwaj; Vivek Yadav; Kaushik Kuche; Pratik Dhake; Sanyog Jain (AAPS PharmSciTech, 2025)

New Strategies to Improve Drug Solubility and Its Impact on Bioavailability: A Patent Review (2015–2024) - Andrés Felipe Pérez Palacios; Jorge Alexis Medina Parra; Daniel Santiago Córdoba Velasco; Diana Carolina Zona Rubio; Izabel Almeida Alves; Diana Marcela Aragón Novoa (AAPS PharmSciTech, 2025)

Mechanistic Modelling of Lidocaine and Prilocaine Absorption from EMLA Cream upon Topical Application using Physiologically Based Pharmacokinetic Modelling - Krishna C. Telaprolu; Eleftheria Tsakalozou; Priyanka Ghosh; Khondoker Alam; Jeffrey E. Grice; Michael S. Roberts; Masoud Jamei; Sebastian Polak; James F. Clarke (AAPS PharmSciTech, 2025)

Artificial Intelligence in Ocular Drug Delivery: Precision Drug Delivery's New Horizon - Vaibhavi Srivastava; Pragya Yadav; Abhishek Yadav; Poonam Parashar (AAPS PharmSciTech, 2025)

Design of Experiments (DoE) Driven Fabrication of Surface Modified Liposomes of Olmesartan Medoxomil for Improved Oral Bioavailability - Sukhada Saraf; Hetal Thakkar; Pranav Shah (AAPS PharmSciTech, 2025)

Optimized Preparation, Functional Evaluation and Performance in Spray Drying of Soybean Peptide-Saccharide Conjugates Prepared by Wet Heating Maillard Reaction - Hong Cheng; Youjie Wang; Zhe Li; Jinzhi Li; Xiao Lin (AAPS PharmSciTech, 2025)

Sustained-release Drug Delivery System of Trazodone Hydrochloride Based on Electrospray Technology: Preparation, Characterization, In vitro and In vivo Evaluation - Chengwei Wang; Haiqiao Wang; Michael Adu-Frimpong; Zhihui Zou; Zhou Jin; Peiqi Lu; Zhenrong Liu; Haojie Tian; Ying Xu; Kailun Yang; Jiangnan Yu; Ximing Xu; et al. (AAPS PharmSciTech, 2025)

Efficacy of Novel Drug Delivery Systems for Insulin Administration and Technological Advances in Diabetes Mellitus: Review - Hossamaldeen Bakrey; Mazin Aboobaida Abdalla Abdelaziz; Fatehalrahman Faris Magbool; Alaa Bakrey; Omer Ibrahim A. Omer; Israa Abdelrahim; Abdulkadir Abdu (AAPS PharmSciTech, 2025)

Enhanced Efficacy and Safety: Cabazitaxel Nanodispersions as a Novel Therapeutic Platform against Prostate Cancer - Youfa Xu; Yanting Kuang; Hang Chen; Junyi Zhou; Bingjie Guo; Ruobei Shu; Jiali Wu; Zongguang Tai; Xin Wu (AAPS PharmSciTech, 2025)

Advances in 3D Printed Microneedles as a Prototype for Skin Targeted Therapeutics in Personalized Dermal Pharmaceuticals - Md Jasim Uddin; Mirza Salman Baig; Amol D. Gholap; Joyeeta Tahseen Khan; Imran A. Sheikh; Yahya E. Choonara; Md. Faiyazuddin (AAPS PharmSciTech, 2025)

Melt-Extruded Microparticles Based On Chitosan-pectin Complex for Delayed Dissolution of Benznidazole - María Sol Magi; Mónica Cristina García; Alvaro Federico Jimenez-Kairuz (AAPS PharmSciTech, 2025)

Novel Hybrid Model to Predict Ribbon Solid Fractions in the Roller Compaction Process - Kiran Iyer; Senthil Kumarasamy; Pankaj Doshi; Allan Hutchins; Patrick Daugherity; Weili Yu; Ashwin Jain; Danielle Bubucis; Matthias Danner; Daniel Schwenk; Holger Schlack (AAPS PharmSciTech, 2025)

Small-Volume Dissolution Testing of Pediatric Mini-Tablets Using Miniaturized USP Apparatuses: Regulatory and Methodological Considerations - Stefanie Broocks; Melanie Gebhardt; Sandra Klein (AAPS PharmSciTech, 2025)
Mini-tablets (MTs) have gained increasing importance as age-appropriate dosage forms, particularly for pediatric patients, due to their ease of swallowing and flexible dosing capabilities. Despite their growing use, regulatory guidance and standardized quality control (QC) methods specifically adapted to MTs, especially extended-release (ER) formulations, are still lacking. This study investigates the suitability of two miniaturized dissolution apparatuses for evaluating ER MTs: a Mini-Paddle system, which is a geometrically downscaled version of the compendial Paddle (USP 2) apparatus, and a small-volume Reciprocating-Holder (USP 7) apparatus. Two commercially available pediatric ER MT drug products containing melatonin and sodium valproate were tested individually and in deliberately manipulated batches to assess the methods’ sensitivity and discriminatory power. The Mini-Paddle apparatus reliably quantified drug release from melatonin MTs but encountered limitations with low-dose sodium valproate MTs, requiring the pooling of multiple units, which masked individual variability. Conversely, the small-volume Reciprocating-Holder enabled sensitive, single-unit testing for both products, effectively detecting batch-to-batch differences despite very low drug loads. Neither apparatus currently holds official compendial status, emphasizing the urgent need for regulatory recognition and standardized methodologies. This study highlights the critical need for sensitive, miniaturized dissolution methods tailored to the unique challenges of MTs to ensure consistent quality, safety, and efficacy, particularly in vulnerable populations. Future work should focus on harmonizing and validating miniaturized dissolution systems to support QC and regulatory acceptance of MT formulations. Graphical Abstract

Personalized Vaginal Drug Delivery through 3D Printing: Techniques, Challenges, and Future Perspectives - Shailvi Shah; Tejal Mehta (AAPS PharmSciTech, 2025)

Current Status on the Convergence of Artificial Intelligence and Formulation Development in Industry: A Review - Siddhesh Warke; Oly Katari; Sanyog Jain (AAPS PharmSciTech, 2025)

Rheological Properties and Process Temperature Prediction for the Hot Melt Extrusion of Artesunate with Soluplus®/Span®20 - Fabio Moyses Lins Dantas; Maria Helena Miguez da Rocha-Leão; Daniel Lins de Sales; André Luís Marcomini; Cesar Augusto Gonçalves Beatrice; Carlos Henrique Scuracchio; Pedro Henrique da Rocha Franco; Alessandra Lifsitch Viçosa (AAPS PharmSciTech, 2025)

Co-Encapsulation of Doxorubicin HCl and Paclitaxel in Nanovesicles for Enhanced Breast Cancer Therapy - Urmila Kafle; Erik Moore; Alexander Lushnikov; Alekha K. Dash (AAPS PharmSciTech, 2025)
Breast cancer is a prevalent malignancy that can metastasize to distant organs if left untreated, leading to significant morbidity. While chemotherapy is commonly used, it has drawbacks like low tissue availability, short circulation time, and toxicity to healthy cells. The objective of this study was to develop and characterize three different nanovesicles loaded with doxorubicin hydrochloride and paclitaxel, hypothesizing that this combination would enhance tumor targeting, reduce dosing and toxicity, and improve patient compliance. A validated UPLC method was developed for simultaneous detection and quantitation of both drugs, showing linearity over 3.13–50 µg/mL. Retention times were 1.53 and 4.06 min for doxorubicin hydrochloride and paclitaxel, respectively. Using thin-film hydration technique, blank and drug-loaded liposomes, transfersomes, and niosomes were formulated. Nanovesicles were characterized for size (150–250 nm), polydispersity index (0.14–0.20), and zeta potential (-0.56 to + 0.54 mV). Drug loading was 2.0–2.5% for doxorubicin hydrochloride and 7.0–7.5% for paclitaxel, with high encapsulation efficiency. Drug release studies showed sustained release for up to 72 h. Nanovesicles remained stable for at least seven days at room temperature and 4⁰C. Cytotoxicity and apoptosis studies using MTT assay and flow cytometry on MDA-MB 231 breast cancer cells revealed that the drug-loaded nanovesicles exhibited potent cytotoxicity and induced apoptotic cell death more effectively than individual drug solutions. In conclusion, this study successfully developed three nanovesicular systems co-loaded with doxorubicin hydrochloride and paclitaxel, demonstrating their potential as effective drug delivery systems for breast cancer treatment. Graphical Abstract Created in BioRender. Dang, L. (2025) https://BioRender.com/h14t77

Development and In Vivo Evaluation of QbD-Assisted Squalene-based Luliconazole Entrapped Ethosomal Gel for the Skin Fungal Infection - Taqdir Singh; Akash Vikal; Preeti Patel; Ghanshyam Das Gupta; Shubham Thakur; Balak Das Kurmi (AAPS PharmSciTech, 2025)

Nanocarrier Strategies in Glioblastoma: Overcoming Barriers to Effective Brain Tumor Therapy - Sara Khan; Md. Faheem Haider; Safia Obaidur Rab (AAPS PharmSciTech, 2025)

Improved Encapsulation and Potential of Liposomal Tosufloxacin via Inclusion in Cyclodextrin - Hemat Mostafa; Hamid Alghurabi; Koki Ogawa; Tetsuya Ozeki (AAPS PharmSciTech, 2025)

Current Strategies in the Development of Nanoformulations to Enhance the Stability of Botox: A Systematic Review - Nazanin Ajdary; Mehdi Shafiee Ardestani; Hasti Nequi Marnani; Babak Eshrati; Tahereh Zadeh Mehrizi (AAPS PharmSciTech, 2025)

Generative Model Enhanced X-ray Computed Tomography Imaging for Pharmaceutical Powder Microstructure Reconstruction and Evaluation - Leqi Lin; Xingyu Zhou; Yuetong Ding; Guangyao Lyu; Xizhong Chen (AAPS PharmSciTech, 2025)

HSPiP and Neuro-Fuzzy Model-Enabled Optimized Nanoemulsions for Nose-to-Brain Delivery of Valproic Acid - Afzal Hussain; Osamah A. Alnemer; Mohammad A. Altamimi (AAPS PharmSciTech, 2025)

A Self-healable Hydrogel for Co-delivery of Hot-Melt Extruded System With Curcumin and Hesperetin Intended for Topical Application - Joanna Szymczak; Kamil Wdowiak; Sylwia Różańska; Jacek Różański; Tomasz Plech; Judyta Cielecka-Piontek (AAPS PharmSciTech, 2025)
Hot-melt extrusion is an effective method for enhancing the solubility of weakly water-soluble compounds through amorphization, but the obtained powder form does not provide sufficient skin adherence or residence time, thus requiring incorporation into a suitable carrier for topical delivery. Hydrogels can serve as an appropriate carriers for such systems, offering additional characteristics such as self-healing and pH-responsiveness. Therefore, our research aimed to develop a hydrogel carrier with distinct features for a hot-melt extruded system containing curcumin and hesperetin, both having anti-cancer activity against skin cancer. We used a double cross-linking method with tannic acid and aluminum ions to prepare three hydrogels with different ratio of these agents, characterized by ATR-FTIR and rheological tests. Swelling studies in buffers of varying pH and in vitro release tests in pH 5.5 showed significant pH-responsive swelling and varying release rates of active compounds, influenced by cross-linking degrees. The prepared hydrogels swelled significantly, with percentages ranging from 170 to 4016%, with the maximum swelling at pH 5.5. Hesperetin release was measured as 84.92 ± 0.03%, 84.21 ± 1.21%, and 80.75 ± 2.76% in formulations H0, H1, and H2, respectively. While the release rate of curcumin increased with the degree of cross-linking, reaching 9.03 ± 0.07%, 26.43 ± 1.16%, and 27.31 ± 2.51%, respectively. In addition, a qualitative analysis with optical microscope confirmed the produced hydrogel's self-healing characteristics. Our findings provide a novel approach to improve the co-delivery of amorphous curcumin and hesperetin compounds to the skin. Graphical Abstract

Exploring co-milling of poorly water-soluble drugs with swellable polymers to enhance the dissolution rate - Nicolas Pätzmann; Josef Beránek; Brendan T. Griffin; Martin Kuentz; Patrick J. O’Dwyer (AAPS PharmSciTech, 2025)
Co-milling with excipients offers an effective solvent-free strategy to enhance the dissolution of drugs in the pharmaceutical industry. Nonetheless, the range of excipients available for co-milling, as well as the selection criteria, remains relatively unexplored. Therefore, this study aims to evaluate the effect of co-milling with crosslinked swellable polymers on the dissolution of poorly water-soluble drugs. A structurally diverse set of crystalline compounds (n = 13) were co-milled with the three commonly used tablet disintegrants: Croscarmellose sodium, sodium starch glycolate and crospovidone. In vitro dissolution profiles were assessed to evaluate the excipient performance and identify crucial drug descriptors relating to co-milling induced dissolution enhancement. All 39 co-milled formulations showed an increased drug intrinsic dissolution rate (IDR), with drug properties such as molecular size and polar surface area showing a positive correlation with the extent of IDR enhancement following co-milling. Moreover, co-milling consistently yielded greater initial dissolution (AUC 0-5 min ) across all excipients compared to milling the drug without an excipient. On average, milling with croscarmellose sodium produced the greatest improvement in the early stages of dissolution for neutral and basic compounds, while sodium starch glycolate was more effective in enhancing the dissolution of co-milled acidic drugs. Furthermore, an assessment within the refined Developability Classification System (rDCS) revealed that co-milling was effective to overcome dissolution rate limitations for all rDCS class IIa drugs. This study establishes a practical framework for the broader application of co-milling with tablet disintegrants and demonstrates its relevance within the latest rDCS paradigm for overcoming dissolution rate-limited absorption. Graphical Abstract

Smart Antifungal Therapy: Lipase-Responsive Ketoconazole and Atorvastatin Co-loaded Poly є-caprolactone Nanoparticles for Cutaneous Candidiasis - Parsa Gul; Asim ur Rehman; Noor Ullah; Khurram Shahzad Munawar; Kifayat Ullah Shah; Naveed Ahmed (AAPS PharmSciTech, 2025)

Mucoadhesive Carbohydrate-Based Polymeric Nanocapsule Loaded with Palbociclib for Enhanced GIT Retention and In Vitro Anticancer Efficacy in MDA-MB-231 Cells - Pooja Khade; Ujala Gupta; Rahul Kumar; Neelesh Kumar Mehra; Pankaj Kumar Singh (AAPS PharmSciTech, 2025)

Novel Capsaicin Nanogel for Arthritic Pain and Inflammation Management: Formulation, In Vitro, Ex-vivo and In Vivo Assessment - Varsha Kadian; Babu Lal Jangir; Pooja Dalal; Sunil Kumar; Anroop Nair; Sweta Dalal; Rekha Rao (AAPS PharmSciTech, 2025)

Long-Chained Fatty Acid-Based Solid Dispersions of Voriconazole as an Effective Strategy For Achieving Sustained Release - Urvi Modasiya; Kiran Dudhat; Sunny Shah; Chetan Borkhataria; Trupesh Pethani; Viral Shah; Chandankumar Pashavan; Gaurav Sanghvi; Akhil Hadiya; Mori Dhaval (AAPS PharmSciTech, 2025)

Overcoming Bioavailability Barriers: Optimized Hybrid Nanocarrier System to Amplify Berberine Absorption via Peyer’s Patches - Shubhangi A. Thool; Varsha B. Pokharkar (AAPS PharmSciTech, 2025)

Utilizing Hot-Melt Extrusion and Spray Drying Techniques for Preparation of Liquid and Solid Cannabidiol Nano-Structured Lipid Carriers Formulations - Iman E. Taha; Mahmoud A. ElSohly; Nourhan Mostafa; Mashan Almutairi; Eman A. Ashour (AAPS PharmSciTech, 2025)
Nanostructured lipid carriers (NLCs) have attracted considerable interest as drug delivery systems capable of enhancing the solubility and oral bioavailability of poorly water-soluble drugs. In our previous work, cannabidiol (CBD)-loaded NLCs prepared by hot homogenization demonstrated improved dissolution and oral bioavailability. In the present study, hot-melt extrusion (HME) was investigated as a rapid and easily scalable alternative method for the preparation of CBD NLCs. Additionally, spray drying was used to convert the prepared CBD NLCs into a solid dosage form. CBD NLCs were prepared using HME at different screw speeds (100, 200, and 300 rpm), followed by probe sonication, and characterized for particle size, entrapment efficiency (EE), and drug release. Spray drying was performed with different carriers (D-lactose, Kollidon® VA 64, maltodextrin 12, and Soluplus®) to evaluate their compatibility and performance. The results showed that the screw speed has an impact on the properties of the NLCs, while probe sonication further reduced particle size, resulting in enhanced entrapment efficiency, and drug release of all formulations. Although NLC produced at a screw speed of 300 rpm was the most stable in both 4 °C and 25 °C. Among the carriers tested for spray drying, maltodextrin achieved nearly complete CBD release, while Soluplus® led to increased particle size and reduced release. Overall, HME combined with probe sonication proved to be a robust approach for the preparation of CBD NLCs, which were successfully converted into solid powder formulations by spray drying, offering a promising strategy for scalable production of CBD NLCs. Graphical Abstract

Highly Soluble Ternary Amorphous Glibenclamide-Arginine-Folic Acid Formulation Using Arginine as a Coformer, and Wettability Agent - Karen Pérez-Carreón; Luz María Martínez; Marcelo Videa; Jorge Cruz-Angeles; Alejandra Flores-Velázquez (AAPS PharmSciTech, 2025)
Pregnant women must take medications to treat or prevent specific health conditions that arise during the gestational period. Glibenclamide (GBC), metformin (MET), or insulin (INS) can be prescribed to treat gestational diabetes; Folic acid (FA) is also prescribed during pregnancy to prevent newborn malformations. GBC and FA have low solubility and, therefore, low bioavailability. Amino acids (AA) have been previously proven to be efficient co-formers in binary systems, enhancing drug solubility in water. In this study, highly soluble pharmaceutical ternary formulations of GBC were prepared with FA and the amino acid arginine (ARG). Although ARG has been previously reported as a co-former in GBC binary co-amorphous formulations, it has not been studied in molar ratios higher than 1:2. The results show that ARG may play a role as a co-former and wettability agent depending on its concentration. Ball milling was chosen to prepare the amorphous systems, testing different molar ratios (GBC:ARG: FA at 1:1:0.4, 1:2:0.4, and 1:10:0.4). The presence of glass transition, broad FT-IR bands, and the absence of X-ray diffraction peaks confirmed amorphization of GBC in the milled samples. Solubility results show that ARG may act as a wettability agent when present in the ratio GBC:ARG:FA 1:10:0.4, since even in the physical mixture, an enhancement of GBC solubility of 897-fold was achieved, and as a co-former since the amorphous GBC-ARG-FA formulation showed an increment of 1287-fold. The enhanced solubility of GBC in these ternary systems makes them potential formulations for simultaneously addressing health conditions through combination therapy with FA. Graphical Abstract

Pharmaceutical Formulations and Analytical Methods of Donepezil - Vu Dang Hoang; Hue Minh Thi Nguyen; Tuan Anh Nguyen; Sanjay Garg (AAPS PharmSciTech, 2025)

Development of Paclitaxel Injection Concentrate for Nanodispersion - Ajay J. Khopade; Malay D. Shah; Bhushan Borole (AAPS PharmSciTech, 2025)

Biopolymeric Composite Films of Hyaluronic Acid and Gellan Gum for Localized and Sustained Azithromycin Delivery in Periodontal Therapy - Kunchorn Kerdmanee; Nuntachai Hanpramukkun; Ratana Charoenwattanasatien; Phakkhananan Pakawanit; Sucharat Limsitthichaikoon (AAPS PharmSciTech, 2025)

Development of Baicalin Loaded Soluplus Based Hydrogel Patch for Wound Dressing - Someshwar D. Mankar; Akash Bhagwat; Suhas S. Siddheshwar; Santosh B. Dighe; Sanjay B. Bhawar (AAPS PharmSciTech, 2025)

A Review on Emerging Technologies in Pharmaceutical Packaging: From Anti-Counterfeiting to Green Solutions - Krishang Sikaria; Amatha Sreedevi; Nandini Srivastava; Virendra S. Ligade; Pradeep Muragundi; Sreedhar D (AAPS PharmSciTech, 2025)
This review article discusses recent innovations and developments in pharmaceutical packaging and its emerging trends in five areas of priority: anti-counterfeiting, drug monitoring, drug quality preservation, sustainability, and patient compliance. The increasing problem of counterfeit medicine has raised the necessity of numerous security technologies to fight the issue. Physical–chemical identifiers, including inks, pigments, and molecular taggants, as well as overt and covert characteristics like holograms, colour-shifting inks, and digital watermarks, assist in verifying the authenticity of pharmaceutical products. New technologies such as carbon dots and microstructural markers in forensic inks add extra security against counterfeiting. Radio Frequency Identification technology assists in product condition tracking, minimizing medical errors, and enhancing patient safety across the supply chain. Colorimetric indicators, like time–temperature indicators and vaccine vial monitors, visually convey environmental conditions and preserve temperature-sensitive drugs' integrity. Drug quality and integrity is another area of importance discussed in the review. Novel packaging technologies, like dual-chamber delivery systems, multilayer constructions, and coatings, offer superior barrier properties and protection against degradation. The review also discusses increasing focus on eco-friendly packaging alternatives, including using renewable, biodegradable, and recycled materials to reduce the ecological footprint of drug packaging. Lastly, the article investigates the role of smart packaging technologies in patient compliance improvement through reminder systems, status indicators, and single-medicine storage units that assist patients in following the prescribed medication regime. Graphical Abstract

Progress and Prospects of Transdermal Treatment of Allergic Skin Diseases with Natural Drugs based on Nanotechnology - Wenfei Lu; Jiansheng Cao; Ying Lv; Meng Li; Ye Tang; Yufei Feng (AAPS PharmSciTech, 2025)

Differential Scanning Calorimetry (DSC) in Solid-State Characterization of Solid Dispersions: A Practical Guide - Shunhua Ding; Rishi M. Shah; Hien V. Nguyen; Tushar Saha (AAPS PharmSciTech, 2025)

A Novel End-to-End Simulation Framework for Internal Flow in pMDIs: Coupled Modeling of Cavitation, Flash Boiling, and Atomization - Mona Mohammadkhani; Janusz Kozinski; Leila Pakzad (AAPS PharmSciTech, 2025)

The Influence of pH and Preservative Agents on Physicochemical and Microbiological Stability of a Flexible Dose/Age-Appropriate Formulation of Enalapril Maleate. A Quality by Design‑Based Optimization - Mauro Morri; María Alejandra Operto; Rubén Maggio; Darío Leonardi; Silvana Vignaduzzo (AAPS PharmSciTech, 2025)

Injectable Hyaluronic Acid Hydrogels Crosslinked by Structure-engineered Aldehyde-functionalized β-Cyclodextrin Derivatives for Long-term Controlled Voriconazole Delivery - Chao Yang; Meng Xin; Yufu Jiang; Wenqian Wang; Wenhui Li; Junlin Quan; Wancong Zhou; Rui Yuan; Zhe Chen; Depeng Shi; Zhijian Ji; Xingxing Yue; et al. (AAPS PharmSciTech, 2025)

A Chrono-Prolific Controlled Release Tripartite Tablet: Case Study of Paracetamol, Diclofenac Sodium and Esomeprazole Magnesium Trihydrate - Kundai R. Mazarura; Pradeep Kumar; Armorel van Eyk; Yahya E. Choonara (AAPS PharmSciTech, 2025)
The work at hand follows the pragmatic design and development of a tripartite controlled release tablet, motivated by the ongoing opioid epidemic and poor adherence to adjunct gastroprotective agents (GPAs) in chronic NSAID users. Taking heed of critical process parameters (CPPs) and critical material attributes (CMAs), a formulation capable of meeting the pre-defined Quality Target Product Profiles (QTPPs) and critical quality attributes (CQAs) was achieved. Delivering 50% of the Paracetamol (PAR) dose within the first 30 min, from an Immediate Release (IR) layer of 250 mg (PAR) for an early onset of analgesia; 100 mg of Diclofenac Sodium (DS) and 250 mg of PAR from the cup, formulated for a delayed and retarded release, and lastly 20 mg Esomeprazole Magnesium Trihydrate (ESM) from a press coated core pill, the latter often prescribed separately. The release mechanism of PAR and DS from the cup after the 2-h mark distinctly followed the Hixson-Crowell model where the geometrical characteristic of the cup was maintained with surface erosion. SEM analysis results prior to and during dissolution confirmed bulk and surface erosion release mechanisms. The obtained ex vivo analysis results showed retarded permeation rates of the tableted APIs compared to the APIs in their pure state. Graphical Abstract

Co-amorphous Approach for Enhancing Rilpivirine Oral Bioavailability using CYP3A4 Inhibitor as a Co-former - Ashwini R. Madgulkar; Mangesh R. Bhalekar; Maryam S. Mulla (AAPS PharmSciTech, 2025)

Strategies to Overcome Challenges in Formulating Tablets from Dried Plant Extracts: a Comprehensive Review - Ewelyn Cintya Felipe dos Santos; Janaina Carla Barbosa Machado; Magda Rhayanny Assunção Ferreira; Luiz Alberto Lira Soares (AAPS PharmSciTech, 2025)

Dissolvable Microneedles with Their Design, Materials, and Limitations in Translation: a Technical Review - Kirthana Gopal; Ramsha Khalid; Syed Mahmood (AAPS PharmSciTech, 2025)

Multistep Machine Learning Pipeline For Polymeric Nanoparticle Design - Rodrigo Fonseca Silveira; Ingrid Araujo de Santana; Ana Luiza Lima; Idejan Padilha Gross; Tais Gratieri; Guilherme Gelfuso; Marcilio Cunha-Filho (AAPS PharmSciTech, 2025)

Preparation and Optimization of Pramipexole Hydrochloride Solid Dispersions to Improve Drug Release and Bioavailability - Yuanyuan Ding; Zhenkun Su; Guodong Liang; Na Sai; Xin Wu; Jianping Chen; Yuheng Ma; Ruijuan Li (AAPS PharmSciTech, 2025)

Retraction Note: Loteprednol-Loaded Nanoformulations for Corneal Delivery by Quality-by-Design Concepts: Optimization, Characterization, and Anti-inflammatory Activity - Burcu Uner; Samet Ozdemir; Cetin Tas; Melike Uner; Yildiz Ozsoy (AAPS PharmSciTech, 2025)

Retraction Note: Revolutionizing Lung Cancer Treatment: Innovative CRISPR-Cas9 Delivery Strategies - Dilpreet Singh (AAPS PharmSciTech, 2025)

Retraction Note: Formulation of Metoclopramide Hydrochloride-Loaded Lipid Carriers by QbD Approach for Combating Nausea: Safety and Bioavailability Evaluation in New Zealand Rabbit - Juste Baranauskaite; Meryem Aydin; Burcu Uner; Cetin Tas (AAPS PharmSciTech, 2025)

Injectables Protein-Based Nanodiscs in Cancer Drug Delivery: From Bench to Clinical Potential - Vimal Patel; Jigar N. Shah; Saloni Dalwadi; Parv Barot; Darshan Vaghela; Megha Patel; Vijaykumar Sutariya (AAPS PharmSciTech, 2025)

Expanding the Arsenal of Nanocarriers Against Parkinson Disease: Success so Far Roads Ahead - Naina Devi; Sonia Dhiman; Chander Parkash; Thakur Gurjeet Singh; Ankit Awasthi (AAPS PharmSciTech, 2025)

Novel Biocompatible Hyaluronic Acid (HA)/Polyvinylpyrrolidone (PVP) Composites Containing Silver Decorated-Zinc MOF Nanoparticles: Antimicrobial Activity, Drug Delivery and Wound Healing - Eman Abdelhakeem; Sally A. Mohamed; Hanan H. Beherei; Mona Moaness; Doaa Hegazy (AAPS PharmSciTech, 2025)
Chronic infected wounds with multi-drug resistant pathogens present severe therapeutic challenges, often leading to prolonged morbidity and impaired healing. To address this, we engineered a multifunctional wound dressing by integrating Voriconazole-loaded silver/zinc MOFs (VOR@Ag/Zn-MOFs) into a hyaluronic acid/polyvinylpyrrolidone (HA/PVP) matrix. The composite was prepared through sequential steps, including preparing a HA/PVP polymer blend via solvent dissolution, synthesizing bimetallic Ag/Zn-MOFs through chemical precipitation, loading VOR into MOF nanocages, and consolidating the composite via chemical crosslinking followed by freeze-drying. Comprehensive physicochemical characterization to confirm MOF stability was implemented through SEM/EDX, confirming uniform nanocage architecture and elemental distribution (Ag/Zn/F), while DLS revealed controlled particle dimensions, and optimal colloidal stability (PDI 0.694; ZP + 39.3 mV). FTIR confirmed structural integrity through preserved polymer peaks (O–H 3400–3200, C = O 1650 cm⁻1), VOR-specific C-F (1400–1200 cm⁻1), and MOF Zn–O bonds (1100–1000/400–600 cm⁻1), verifying non-covalent integration without degradation. XRD further verified the crystalline framework integrity. In-vitro release studies demonstrated sustained biphasic release (44.2% ± 5.9 burst within 6 h; up to 77.1% ± 1.8 controlled release over 360 h). The composite demonstrated exceptional antimicrobial synergy, including potent antifungal activity against Candida albicans (MFC 1.4 µg/mL, 214-fold lower than free VOR) with microscopically-confirmed cell wall disruption, and broad bacteriostatic activity (MIC range 8,500–17,000 µg/mL against Gram-positive and Gram-negative pathogens). Critically, it achieved complete fungal clearance within 24 h. Simultaneously, it accelerated tissue regeneration, showing outstanding fibroblast biocompatibility (IC₃₀ > 3,000 µg/mL; 6,000-fold safety margin) and enabling marked wound closure within 72 h in the wound healing study. By converging triple-action mechanisms, including metal ion synergy (Ag⁺/Zn2⁺), targeted azole delivery, and HA/PVP-mediated pro-regenerative signaling, this platform uniquely eliminates resilient infections and restores wound integrity that was previously unattainable with conventional azole therapies. Graphical Abstract

Oleic acid Enriched Leciplexes as Novel Mucoadhesive Cationic Nanocarriers of Agomelatine for Glaucoma Treatment - Mai Ahmed Tawfik; Sadek Ahmed; Rania Moataz El-Dahmy; Diana E. Aziz (AAPS PharmSciTech, 2025)
Agomelatine (AGO) is a dual action drug. Being serotonin receptor antagonist, AGO is orally administered for depression treatment. Here in, AGO was used for intraocular pressure management due to its agonistic activity on the melatonin receptors in the eyes. AGO is a BCS II drug, with low oral bioavailability and massive first-pass metabolism. Oleic acid enriched leciplexes were investigated as novel mucoadhesive cationic nanocarriers to improve AGO’s ocular bioavailability and prolong its pharmacological effect. Twenty-four AGO loaded leciplexes were fabricated by single-step procedure. AGO: lipid ratio, surfactant: phosphatidyl choline ratio, cationic surfactant type, permeation enhancer type were investigated. For optimization; in-vitro assessment of size, homogeneity, surface charge, drug entrapment and in-vitro release was conducted. The optimum system was further examined for crystallinity, compatibility, morphology, pH, refractive index, surface tension and stability. L20 developed at a drug: lipid ratio of 1: 20, cetyltrimethylammonium bromide and phosphatidyl choline at a ratio of 1:5 respectively and 0.25% w/v oleic acid was the optimum system with respect to shape and PS (spherical, 491 nm), PDI (0.29), ZP (31.1 mV), EE (81.8%), in-vitro release (Q 2h ; 34.9%, Q 8h ; 91.2%), crystallinity, pH (6.3), refractive index (1.24), surface tension (46.2 mN/m) and stability. AGO pharmacodynamic and histopathological studies were conducted in rabbits. Compared to AGO dispersion, elevated maximum IOP reduction (74.2%), prolonged mean residence time (12.88 h), enhanced bioavailability (3 folds) and normal histopathological micrographs proved the potential of L20 leciplex in improving and sustaining the ocular bioavailability of AGO and maintaining its safety. Graphical Abstract

Novel Quercetin-Ascorbic Acid Nano Cocrystals: A Carrier-free Strategy for Enhancement of Solubility, Topical Anti-oxidant Activity and Cytotoxicity - Najam ul Hassan Jawa; Nasir Abbas; Hafiza Nasreen Aslam; Hafsa Afzal; Misbah Hameed; Nadeem Irfan Bukhari; Sumera Latif (AAPS PharmSciTech, 2025)

Effect of Surfactants on Oral Delivery of Nanoemulsions Containing Fexofenadine, a Substrate for P-glycoprotein - Ikki Shibazaki; Yuri Ikeuchi-Takahashi; Mayumi Ikegami-Kawai; Yasuko Obata (AAPS PharmSciTech, 2025)

Enhanced Ocular Delivery of Itraconazole via a Self-Emulsifying Drug Delivery System: Improved Antifungal Activity and Cellular Uptake - Sukannika Tubtimsri; Yotsanan Weerapol (AAPS PharmSciTech, 2025)

Fabrication of Gastroretentive and Extended-Release Famotidine Floating Tablets via Fused Deposition Modeling - Esraa Al Shawakri; Eman A. Ashour; Rasha M. Elkanayati; Mashan Almutairi; Sundus Omari; Nouf AlShammari; Michael A. Repka (AAPS PharmSciTech, 2025)
Famotidine suffers from low oral bioavailability due to poor aqueous solubility, short half-life, and limited gastric retention. This study aimed to develop gastro-retentive floating tablets of famotidine using hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing approach to enhance its solubility, prolong gastric residence, and achieve extended drug release. Famotidine was incorporated into various polymeric carriers, including hydroxypropyl cellulose (HPC LF) and hydroxypropyl methylcellulose (HPMC E5), to produce drug-loaded filaments using an 11 mm twin-screw co-rotating extruder. The filaments were subsequently 3D-printed into low-density, hollow tablets to achieve prolonged gastric floatation. The solid-state characterization by differential scanning calorimetry (DSC) revealed the absence of famotidine’s crystalline melting peak in both filaments and 3D-printed tablets, suggesting amorphization within the polymer matrix. FTIR spectroscopy indicated hydrogen bonding interactions between famotidine and polymer hydroxyl groups, supporting the stabilization of the solid dispersion. The lead formulation demonstrated excellent buoyancy of about nine hours and extended drug release in 0.1 N HCl, confirming the potential of the system for extended gastric retention. This work highlights the utility of HME-FDM 3D printing for developing tailored, gastro-retentive dosage forms that enhance the performance of poorly soluble drugs like famotidine through amorphous solid dispersion and formulation-driven design. Graphical Abstract

Investigations on the Spatial Dust Distribution for Emission Site Localization in Containment - Hendrik Küllmar; Martin Schöler; Jonas Brügmann; Claudia S. Leopold (AAPS PharmSciTech, 2025)
Dustiness and the spatial distribution of dust are major problems when working with highly active pharmaceutical ingredients. Therefore, the aim of this study was to develop a chamber setup that allows a reproducible atomization of small powder quantities and the detection of not only dustiness but also the spatial distribution of airborne dust at extremely low concentrations, to prove that an emission site may be localized with stationary sampling even in a confined space. For this purpose, the time required for evacuation of the chamber setup was determined with fuming sulfuric acid. In subsequent atomization experiments, the safe surrogate acetaminophen was used. The spatial distribution of the surrogate was detected with nine IOM samplers (Institute of Occupational Medicine) and its quantification was carried out via HPLC. A linear tendency of the quantity of aerosol formed in dependence of the sample mass was demonstrated. In addition, significant differences between individual spots of detection and thus a spatial distribution in the detection chamber was observed. These results indicated a strong convective mass transport within the chamber setup. To verify these results, the airflow used for atomization was simulated using Computational Fluid Dynamics, confirming the convective mass transport and the spatial distribution of the airborne acetaminophen dust. In summary, it was shown that an emission site may be localized based on stationary exposure data even at concentrations as low as those mandatory in the contained manufacture of HPAPI-containing pharmaceuticals. Graphical Abstract

Enhanced Tumor Treatment Outcomes of PEGylated Liposomal Gefitinib in Non-Small Cell Lung Cancer: A Comprehensive Preclinical Evaluation with Superior Therapeutic Efficacy - Rajeshkumar S. Palva; Jolly R. Parikh; Rajnikant M. Suthar; Musaratafrin Saiyed; Mitali Patel; Prajesh Prajapati; Umang H. Shah (AAPS PharmSciTech, 2025)

Dissolution Amelioration by Small Amounts of HPMC in the Difficult-to-solve Drug Combination Baicalein-imperatorin Co-Amorphous System: Dispersion and Crystallization Inhibition - Tong Su; Xinli Liang; Qieying Jiang; Yu Tong; Mubarak G. Bello; Gonglong Li; Zhenggen Liao (AAPS PharmSciTech, 2025)

The Road to Precision Nanomedicine: An Insight on Drug Repurposing and Advances in Nanoformulations for Treatment of Cancer - Yasmina Elmahboub; Rofida Albash; Sadek Ahmed; Salwa Salah (AAPS PharmSciTech, 2025)
Cancer remains one of the most significant global health challenges, with its burden continuing to rise. The limitations of conventional anticancer therapies caused by the lack of tissue selectivity, demands urgent development of safer and more selective therapies to target tumors. Identifying the fundamental cancer hallmarks provided a comprehensive understanding of cancer biology for effective tumor targeting, encompassing tumor-promoting inflammation, metabolic reprogramming, immune evasion, genomic instability, phenotypic plasticity, epigenetic reprogramming, and polymorphic microbiomes. Moreover, drug repurposing is a cost-effective and time-saving method for cancer therapy that accelerates the drug discovery process by reusing drugs for new indications. Current research is focusing on combining drug repurposing with nanocarriers that enhance tumor targeting, reduce the side effects, and improve the bioavailability of the drug in a single nanoformulation. This article analyzes various types of nanoparticles encapsulating different classes of drugs, such as phenelzine, fexofenadine, telmisartan, losartan, metformin, canagliflozin, atorvastatin, and fenbendazole, highlighting their anticancer effects and the influence of nanocarriers on the drug’s therapeutic effect. Results revealed that drug-encapsulated nanoparticles enhanced antitumor effects compared to the free drug solutions. This is attributed to the synergism from the nanocarrier’s functionalization, sustained drug release, and improved cellular uptake within tumors that leads to targeting multiple cancer hallmarks. Additionally, this review highlights the present challenges in the clinical translation of nanoformulation and demonstrates how artificial intelligence may facilitate drug screening and identification, therapeutic optimization, and large-scale manufacture. Finally, using these technologies in combination with drug repurposing presents a promising direction for advancing cancer treatment. Graphical Abstract

A Comparative Study of the Influence of Lipid Composition on Stability, In Vitro Release, and Antioxidant Activity of Quercetin-loaded Ceramide-containing Liposomes for Topical Delivery - Ioannis Tsichlis; Veatriki-Despoina Koufonikola; Chrysi Chaikali; Sophia Hatziantoniou; Costas Demetzos (AAPS PharmSciTech, 2025)
This study investigates the influence of phospholipid saturation by comparing hydrogenated soy phosphatidylcholine (HSPC) and egg yolk phosphatidylcholine (EPC) on the physicochemical characteristics, colloidal stability, drug release behavior and antioxidant activity of quercetin-loaded ceramide-containing liposomes for topical delivery. Liposomes composed of EPC:Cer:Que and HSPC:Cer:Que were prepared by thin-film hydration followed by sonication. The nanosystems were studied for particle size, polydispersity index, ζ-potential, and entrapment efficiency. Colloidal stability was evaluated under mechanical stress, accelerated aging, and long-term storage, while in vitro drug release, drug retention, and antioxidant activity were assessed under simulated skin conditions. Incorporation of ceramides into EPC bilayer reduced stability issues associated with unsaturated phospholipids and maintained a fluid structure, promoting drug release. Both formulations exhibited enhanced colloidal stability with EPC-based liposomes maintaining their properties at all conditions, whereas HSPC-based liposomes showed increased particle size following mechanical stress. HSPC-based liposomes demonstrated higher quercetin entrapment efficiency (63 ± 5%), improved retention over time (75% at 90 days), and a more sustained release (45% at 480 min). EPC-based ceramide-containing liposomes exhibited faster release (50% at 240 min), resulting in greater antioxidant activity as indicated by DPPH assay (0.474 ascorbic acid equivalents), while FRAP assay results were comparable for both formulations (0.012 Fe 2+ equivalents), indicating consistent ferric reducing potential after release. These findings highlight the significance of phospholipid composition in liposome behavior and provide insights into the design of stable and effective ceramide-containing nanosystems for topical delivery of poorly water-soluble compounds such as quercetin, with potential applications in managing photoaging, inflammation, and wound healing. Graphical Abstract

Advances in Pharmaceutical Cocrystals and Nano-Cocrystals: Strategies for Enhancing Solubility and Translating to Clinical Use - Roshan P. Rao; Jawahar Natarajan; Samanwita Khanra; Jey Kumar Pachiyappan; Imrankhan Nizam; Akshay Muralidhara; Jubie Selvaraj; S. Selvamuthukumar (AAPS PharmSciTech, 2025)

A Novel Felbinac Transdermal Patch with High Permeability: Design, Development and Evaluation - Li Qin; Cheng Liu; Ran Bai; Zhining Zhao; Yinghua Sun; Peng Zhang (AAPS PharmSciTech, 2025)

Inhalable Inclusion Cocrystal of Exocarpium Citri Grandis Volatile Oil for Treatment of Acute Lung Injury - Ying Luo; Zeyu Li; Guilan Wang; Ergang Liu; Huan Shen; Guilong Zhao; Ping Zhao; Yongzhuo Huang (AAPS PharmSciTech, 2025)

Formulation and Optimization of Memantine-Loaded PEGylated Single-Walled Carbon Nanotube Dispersions - Hoa Le; Hai V. Nguyen; Amos Abioye; Adeboye Adejare (AAPS PharmSciTech, 2025)

Factors Influencing the Dispersibility of Glycopyrronium Bromide and Indacaterol Maleate – Combined In Vitro and In Silico Study - Aleksandra Rzewińska; Jakub Szlęk; Ewelina Juszczyk; Katarzyna Mróz; Olga Czerepow-Bielik; Maciej Wieczorek; Przemysław Dorożyński (AAPS PharmSciTech, 2025)
The development of dry powder inhalers (DPIs) for pulmonary drug delivery is complex, requiring optimization of variable factors to ensure effective lung deposition. This study investigates the factors influencing the dispersibility of glycopyrronium bromide (GLP) and indacaterol maleate (IND) in adhesive mixtures using both in vitro and in silico approaches. The formulation was designed to match the reference listed drug (RLD), using lactose and magnesium stearate as excipients. Key variables examined included mixing energy, carrier particle size distribution (PSD), and active pharmaceutical ingredient (API) particle size characteristics across multiple suppliers. A Next Generation Impactor (NGI) was employed to assess the aerodynamic particle size distribution (APSD) of 67 formulations. The collected impactor data were analyzed using machine learning (ML) models, leveraging the h2o AutoML framework. Stacked ensemble models demonstrated high predictive accuracy (R 2 : 0.940 for GLP, 0.969 for IND), identifying key formulation parameters affecting dispersibility. SHAP analysis revealed that GLP dispersibility was influenced primarily by GLP PSD (d90, d50, SPAN), lactose d10, and mixing energy, while IND was more dependent on lactose PSD and its own particle size. The findings confirm that both APIs interact with each other within the formulation, significantly impacting their reciprocal deposition profiles. These insights highlight the challenge of developing bioequivalent DPI formulations and emphasize the importance of PSD control, mixing energy optimization, and advanced ML modeling in predicting therapeutic equivalence. The study provides a predictive framework to support the development of generic inhalation products, improving regulatory approval pathways and ensuring effective pulmonary drug delivery. Graphical Abstract

The Fundamentals of the Analysis of Cascade Impactor Data for the Characterization of Aerodynamic Particle Size Distributions (APSDs) in the Testing of Orally Inhaled Drug Products (OIPs) - Daryl L. Roberts; Jolyon P. Mitchell (AAPS PharmSciTech, 2025)

In Vivo Pharmacodynamic and Pharmacokinetic Assessment of Cannabidiol-loaded Camel Milk Exosomes in Doxorubicin-resistant Triple-negative Breast Cancer Xenografts - Mounika Aare; Sandeep Chary Padakanti; Mandip Singh (AAPS PharmSciTech, 2025)

Amorphization of Albendazole Using Organic Acid-based Solid Dispersions for Improved Dissolution: A Solvent-free Approach - Nilesh Jambukiya; Kiran Dudhat; Sunny shah; Chetan Borkhataria; Trupesh Pethani; Ramesh Parmar; Viral Shah; Gaurav Sanghvi; Mori Dhaval (AAPS PharmSciTech, 2025)

Integrated Analytical Techniques to Investigate the Effect of the Freezing/Thawing Cycles on the Non-replicating Recombinant Chimpanzee Adenovirus Viral Vector COVID-19 Vaccine - Moushira M. Mostafa; Nourhan H. AbdelAllah; Eman S. Elzanfaly; Ghada A. Sedik (AAPS PharmSciTech, 2025)
The chimpanzee adenovirus-vectored vaccine developed by the University of Oxford (ChAdOx1 nCoV-19) showed good stability when stored in refrigerator. However, the vaccine manufacturer prefers its transportation in frozen condition. Data regarding the stability of the vaccine after exposure to repeated freezing processes have not been explored yet. In the present study, different batches were exposed to 3 repeated freezing/thawing cycles. An orthogonal testing using various techniques was employed to assess any induced changes in the properties of the vaccine in comparison with control samples. Physicochemical properties, including appearance, pH, and molecular size distribution by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were evaluated. Anion-exchange chromatography (AEC) was used for the determination of virus particles, and DNA to-protein ratio to study the biochemical attributes of the vaccine. Furthermore, the immunological properties were evaluated employing in-vivo test to compare the results obtained by the testing protocol to the vaccine efficiency in animals. Results revealed that the physicochemical attributes of the vaccine were not affected by the applied freeze–thaw cycles. Although the virus particles measured for thawed samples by AEC were below the specified limits of 0.7 – 1.3 × 10 11 VP/mL, the values of DNA to protein ratio remained unaffected (1.1 – 1.5), and there was no reduction in the in vivo potency of the tested samples. Statistical analysis of the results of the quantitative tests implied that the vaccine could withstand up to three successive freezing and thawing cycles during transportation without significant loss in its structural integrity and biological potency. Graphical Abstract

Effects of Roller Compaction on Dissolution of Granules and Tablets Captured in the Development of Two Real Pharmaceutical Formulations - Nikita Marinko; Stephanie Michelle Medrano; Tomáš Krpelan; Zuzana Chayka; Kateřina Budková; Vít Zvoníček; Petr Zámostný (AAPS PharmSciTech, 2025)
Roller compaction is often utilized as the first step to improve flow properties and homogeneity of pharmaceutical mixtures. Since the dry granulation process is less complicated than its counterparts in the industry, it is possible to perform screening experiments readily to investigate granulate quality for further operations. In this study, the aim of the investigation focused on the effect of roller compaction on the dissolution of granules and tablets of two pharmaceutical formulations that contain APIs of different biopharmaceutical classification. This study underscores the benefits of granule dissolution testing as a crucial early-stage technique for optimizing granulate quality and facilitating progression through formulation manufacturing operations. For active pharmaceutical ingredients characterized by poor dissolution properties, this approach provides valuable insights during the initial development phases. By integrating granule dissolution testing into the development process, product manufacturability can be enhanced and optimal product performance can be ensured. Graphical Abstract

3D-printed Gabapentin-loaded Implants for Sustained Release: Leveraging 3D Printing and Hot Melt Extrusion (HME) for Customizable Drug Delivery - Baher A. Daihom; Hala M. Abdelhakk; Mohammed Maniruzzaman (AAPS PharmSciTech, 2025)
Pediatric neuropathy poses significant challenges in pain management due to the limited availability of approved pharmacological options. Gabapentin, commonly used for neuropathic pain, offers therapeutic potential but necessitates careful dosing due to its variable bioavailability. This study investigates the integration of Hot Melt Extrusion and Fused Deposition Modeling in the development of polycaprolactone-based implants for sustained release of Gabapentin. A preliminary screening using Vacuum Compression Molding optimized formulations for Hot Melt Extrusion, enhancing material efficiency and process streamlining. Filaments with a diameter of 1.75 mm were successfully extruded and used for 3D printing of Gabapentin implants. Several tests were undertaken to characterize the prepared filaments and implants. Energy-Dispersive X-ray spectroscopy confirmed the uniform distribution of Gabapentin within the implant matrix. Solid-state characterization techniques were employed to assess the compatibility of implant components and to verify the solid-state of Gabapentin within the implant structure. In vitro drug release studies were conducted. Filaments with varying drug loadings were examined, revealing that a 20% w/w drug loading achieved an optimal balance between rapid and sustained release. Additionally, implants with different infill densities were analyzed, demonstrating that varying infill densities allow control over the amount and percentage of drug released. The 100% infill density resulted in the most sustained release effect, achieving approximately 40% drug release by day 28. These findings underscore the feasibility of 3D printing for producing personalized implants, emphasizing the potential for tailored drug release profiles to meet specific needs of pediatric patients. Graphical Abstract

Retraction Note: Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid - Mahboubeh Ebrahimian; Sahar Taghavi; Maryam Ghoreishi; Shahrzad Sedghi; Sara Amel Farzad; Mohammad Ramezani; Maryam Hashemi (AAPS PharmSciTech, 2025)

The Impact of Different Radiopacifying Agents on the Elution and Mechanical Properties of Vancomycin-loaded Bone Cements - Arezou Mashak; Mohammad Atai; Azizollah Nodehi (AAPS PharmSciTech, 2025)

Tabletability Enhancement of Acetaminophen Coated with a Nanocellulose Suspension using a Fluidized Bed - Zhixing Lin; Maxx Capece (AAPS PharmSciTech, 2025)

In-situ Nanolipoidal Gel of Stiripentol for Intranasal Administration: Preclinical Evidence of Enhanced Biopharmaceutical and Therapeutic Outcomes - Harshada Mahajan; Pradip Nirbhavane; Shailesh Chalikwar; Kailas K Moravkar (AAPS PharmSciTech, 2025)

Voriconazole Loaded Spanlastics: Design, Formulation, Optimization, and Randomized Controlled Clinical Insights for Vulvovaginal Candidiasis Therapy - Nermin M. Sheta; Rehab Nabil Shamma; Raghda R. S. Hussein; Sara Abdallah Mohamed Salem; Lamiaa N. Abdelaty; Mahmoud M. Abd El Gawad; Khaled M. Abdel-Haleem (AAPS PharmSciTech, 2025)
Voriconazole, a potent antifungal agent, has emerged as a promising candidate for managing vulvovaginal candidiasis. The market availability of voriconazole as tablets or injections, along with potential side effects, highlights the need for a successful alternative delivery system. Through comprehensive experimental design, voriconazole-loaded spanlastics were developed using a 3 2 -factorial design. The optimized system based on factorial outcomes exhibited desirable characteristics in terms of entrapment efficiency (74.31 ± 0.39%), vesicle size (246.4 ± 2.2 nm), polydispersibility index (0.369 ± 0.01), & zeta potential (-37.5 ± 0.17 mV). Further characterization for the optimized system was performed in terms of transmission electron microscopy, Fourier transform infrared spectroscopy, and in-vitro antifungal assessment, where the latter showcased the potent effectiveness of voriconazole against various Candida species. Moreover, the integration of the optimized voriconazole-loaded spanlastic system into a gel was implemented for the assessment of ex-vivo permeation through the vaginal mucosa of rats, where the optimized system gel revealed a remarkable 1.3-fold enhancement in permeation relevant to the control VCZ gel. Notably, the clinical performance of optimized system gel was involved in a randomized controlled study for assessment of safety and efficacy in comparison to a market product (Canesten ® 2% clotrimazole). Clinical evaluation revealed that the optimized VCZ-loaded SP gel and the market product, Canesten. (2% clotrimazole) exhibited comparable efficacy in terms of clinical satisfaction, side effects, and time to clinical cure from VVC. These findings highlight the potential of the optimized system as a promising approach for improved treatment outcomes in women with vaginal candidiasis with no adverse effects. Graphical Abstract

LC-ESI-HRMS-Based Evaluation of Antioxidants as Additives to Inhibit Genotoxic Nitrosamine Formation in Metformin Hydrochloride Tablets - Aishwarya Dande; Nikhil Pallaprolu; Sangita Gadilohar; Sushmita Mishra; Rajkumar Malayandi; Subramanian Natesan; Abhishek Sahu; Murali Kumarasamy; Ravichandiran Velayutham; Ramalingam Peraman (AAPS PharmSciTech, 2025)

Stimuli-responsive Hydrogels for Targeted Antibiotic Delivery in Bone Tissue Engineering - Jayendra Kumar; Tolepbergenova M.; Abdugani Musayev; Aizhan Danyshbayeva; Lazzat Begimbekova; Hitesh Kumar; Terlikbayeva Gulnar; Pawan Kumar; Shamim Shamim (AAPS PharmSciTech, 2025)

Micro-Flow Imaging: Enhanced Precision in Clarity Assessment of Traditional Chinese Medicine TCM Injections Compared to Light Obscuration and Visual Inspection - Le Yang; Sijun Wu; Haibin Qu (AAPS PharmSciTech, 2025)

Electromagnetic Field Influence on the Bioavailability and Accumulation of Ketoprofen - Karolina Zyburtowicz-Ćwiartka; Anna Nowak; Anna Muzykiewicz-Szymańska; Łukasz Kucharski; Maciej Konopacki; Rafał Rakoczy; Paula Ossowicz-Rupniewska (AAPS PharmSciTech, 2025)
The growing interest in transdermal drug delivery systems has led to the exploration of novel methods to enhance skin permeability and drug bioavailability. In this study, the effects of various electromagnetic fields (EMF) configurations on the physicochemical properties and transdermal performance of ketoprofen, a commonly used nonsteroidal anti-inflammatory drug, were investigated. Ketoprofen samples were exposed for 8 hours to oscillating, pulsed, static (positive and negative polarity), and rotating magnetic fields. Subsequent analyses included FTIR spectroscopy, XRD, thermal stability, aqueous solubility, lipophilicity (log P), skin permeability (measured using Franz diffusion cells), and accumulation in porcine skin. The results showed that, while the molecular structure of ketoprofen remained unchanged, exposure to a magnetic field induced subtle changes in the crystal structure, thermal behaviour, solubility, and lipophilicity properties. Among all tested conditions, pulsed magnetic fields (particularly PMF 10/10) and rotating fields (RMF 50 Hz) significantly improved both transdermal permeation and dermal accumulation. These enhancements correlated with increased solubility, suggesting that EMFs may modulate molecular interactions with biological barriers. In contrast, static fields with negative polarity reduced the transport and retention of drugs in skin tissue. This study confirms the potential of electromagnetic stimulation as a non-invasive and effective strategy for enhancing the dermal delivery of poorly permeable active substances, such as ketoprofen. Optimization of EMF parameters may provide a promising direction for the development of advanced transdermal drug delivery systems. Graphical Abstract

Correction: In Vivo Evaluation of Almotriptan Malate Formulation Through Intranasal Route for the Treatment of Migraine: Systematic Development and Pharmacokinetic Assessment - Shubham Gupta; Akhil Perla; Abhishek Roy; Jyotsna G. Vitore; Bharathi K; Sagar Salave; Dhwani Rana; Amit Sharma; Rajeshwari Rathod; Hemant Kumar; Derajram Benival (AAPS PharmSciTech, 2025)

Granule Moisture Content Prediction During Fluid Bed Drying - Paloch Chinwattanawongwan; Narueporn Sutanthavibul; Oran Kittithreerapronchai (AAPS PharmSciTech, 2025)

Palatable Orally Disintegrating Tablets of Losartan Potassium Developed by Spray-drying Technique and Direct Compression Intended for Pediatric Use - Candela Juan; Noelia Gonzalez Vidal; Loreana Gallo (AAPS PharmSciTech, 2025)

Development of a pH Gradient Dissolution Condition to Predict the Behavior of Delayed Release Formulations under Fed In Vivo Condition - Juilee Kulkarni; Usha Nayak; Bibhuranjan Panigrahi; Sajeev Chandran (AAPS PharmSciTech, 2025)

Thermoreversible Ionogel for Enhanced Nose-to-brain Delivery of Tetrabenazine Hydrochloride: Optimization by Central Composite Design and In Vitro Ex Vivo Evaluation - Namdeo Jadhav; Manali Chavan; Prathamesh Patil; Pranali Takale; Megha Mane; Suhas Mohite (AAPS PharmSciTech, 2025)

An Updated Perspective on Skin Disease Therapy: From Conventional Methods to Nanocarrier Innovations - Riya Shivgotra; Bindu Soni; Parminder Kaur; Anshuka Sharma; Varun Singh; Nitin Partap; Hossamaldeen Bakrey; Subheet Kumar Jain (AAPS PharmSciTech, 2025)

Cab-O-Sil®M-5P Integrated Solidified Phytosomes: A Novel Strategy to Enhance the Solubility, In Vitro Dissolution and Pharmacokinetic Performance of Ferulic Acid - Amol S. Warokar; Darshan R. Telange; Bhawna S. Dumbhare; Umesh B. Telrandhe (AAPS PharmSciTech, 2025)

Targeted Drug Delivery for Breast Cancer using Functionalized Liposomes: Preparation Methods, Challenges, and Clinical Translation - Amlan Bishal; Priyadarshini Paul; Sayan Bera; Dipsikha Patra; Bratati Bandyopadhyay; Biplab Debnath; Kazi Asraf Ali (AAPS PharmSciTech, 2025)

Advancements in Liposomal Drug Delivery Systems for Paediatric Neurological Disorders: A Comprehensive Review - Parvathy Hari; Safa A. Vahab; Vrinda S. Kumar (AAPS PharmSciTech, 2025)

Evaluating 3D-Printed Pre-separator Inserts in a Fast Screening Impactor for Physicochemical Characterization of Fine Particle Dose Release from Dry Powder Inhalers - Nathan A. Reed; Roee Dar; Nicholas Holtgrewe; Leo N. Y. Cao; Xiaofei Liu; Denise S. Conti; Bryan Newman; Elizabeth Bielski; Jason D. Rodriguez; Changning Guo (AAPS PharmSciTech, 2025)

Development, Characterization, and in vitro Efficacy Evaluation of an Inhalable H1B Antimicrobial Peptide Formulation for Treating Non-Small Cell Lung Cancer - Alec M. Diorio; Apoorva Daram; Nandhini Sriram; Thomas Lund; Alan B. Watts; Nitesh K. Kunda (AAPS PharmSciTech, 2025)

Rational QbD-based Assessment of Formulation Ingredients' Impact on Sustainable Sunscreen Physical Stability - Larissa Carniel; Marina Gomes; Giovana Carolina Bazzo; Helena Margarida Ribeiro; Joana Marto; Bianca Ramos Pezzini (AAPS PharmSciTech, 2025)

Novel Pathways for Non-invasive Laser-assisted Drug Delivery: A Critical Review - Dilpreet Singh; Lalu Mohammad Irham (AAPS PharmSciTech, 2025)

In-vitro Evaluation of p-Sulfonatocalix[n] arenes (SCnA) as Novel Excipients Using a Vectorized BCS Approach - Lihua Tan; Zhongli Jing; Na Li; Xuan Yu; Yi Liu; Meng Wang; Xiaoliang Ren (AAPS PharmSciTech, 2025)

Fast-Dissolving Pullulan Film as a Solid Dosage Form for Sublingual Administration of Nifedipine-Loaded Nanocapsules - Bárbara Felin Osmari; Giovana Aime Medeiros; Lucas Saldanha da Rosa; Nadine Lysyk Funk; Paulo Ricardo de Souza; Ruy Carlos Ruver Beck; Letícia Cruz (AAPS PharmSciTech, 2025)

Influence of Hydrophobic Ion Pairing on Formulation Performance of Liraglutide in PLGA Microspheres - Jyotsna G. Vitore; Varla Yalamanda; Devendra Singh Tomar; Satish Rojekar; Dhwani Rana; Derajram Benival (AAPS PharmSciTech, 2025)

Integrating Quality by Design (QbD) in Phytosomal Drug Delivery: A New Era in Precision Phytotherapy - Sumant Kumar; Omar Awad Alsaidan; Sami I. Alzarea; Akshay Kumar; Suresh Babu Kondaveeti; Diksha Sharma; Mohit Kumar; Devesh Kumar (AAPS PharmSciTech, 2025)

Nanovesicular Drug Delivery Systems for Rare Ocular Diseases: Advances, Challenges, and Future Directions - Shaheen Sultana; Mohammad Yusuf; Vikram Sharma (AAPS PharmSciTech, 2025)

Hot Melt Extrusion Technology in Taste Masking - Geetha Nayak; Usha Y. Nayak (AAPS PharmSciTech, 2025)
Hot melt extrusion (HME) is a widely used method of taste masking in medication formulations, notably for bitter Active Pharmaceutical Ingredients (APIs). This continuous, solvent-free technique successfully wraps APIs within a polymer matrix, forming a barrier that considerably decreases bitterness perception. These advantageous properties of HME in taste masking are especially important for pediatric, geriatric, and veterinary formulations, where palatability is critical. The technique entails melting a polymer matrix and combining it with the medicine, followed by extrusion to make granules or dosage forms. The efficacy of taste masking is dependent on selecting acceptable excipients and ensuring their compatibility with the medicine. Temperature, screw speed, and drug-to-polymer ratio are critical process parameters that must be tuned. Various screw configurations can influence the physical condition of the API during extrusion, increasing taste-masking efficacy. Future advances in HME technology are expected, with a focus on enhancing taste masking for a broader range of APIs. Innovations in the study of polymers and the combination of process analytical technology (PAT) will significantly enhance the effectiveness and reliability of flavor-masked formulations, resolving the important need for patient-friendly drugs that are taken orally.

Exploring the Therapeutic Potential of Lipid Nanocarriers in Psoriasis Management: Advances and Applications - Atif Husain; Poonam Kushwaha; Archita Kapoor; Priyanka Singh (AAPS PharmSciTech, 2025)

Exploration of Predictive Potential of AI-enabled Portable System in Anticancer Drug Delivery: A Comparative Study with Modified Gompertz like Biphasic Response Model - Subeel Shah; Kapil Saraswat; Charu Misra; Poonam Negi; Kaisar Raza (AAPS PharmSciTech, 2025)

Alternative Syringe and Needle Design for Clog-free Delivery of High-concentration Suspensions - Kavin Kowsari; John Cline; Steven C. Persak; Guangli Hu; Robert Berger; Jeffrey C. Givand; Sahab Babaee (AAPS PharmSciTech, 2025)

Integration of Design of Experiments for the Development and Evaluation of Sulfasalazine Loaded Hybrid Albumin Chitosan Based Polymeric Nanocarriers - Sushrut Marathe; Rohit Joshi; Rongbing Yang; Gauri Shadambikar; André S. Bachmann; Mahavir Bhupal Chougule (AAPS PharmSciTech, 2025)

Nanotechnology in Uveal Melanoma: Cutting-Edge Advances to Halt Progression and Metastasis - Rohit Bhawale; Omar Khan; Ravindra Vasave; Rati Yadav; Neelesh Kumar Mehra (AAPS PharmSciTech, 2025)

Phospholipid-Drug Conjugates in Cancer Therapy: Emerging Paradigms and Future Directions - Kiran Dudhat; Harsh Pirojiya; Krupali Bhalala; Dhaval Mori; Bhupendra Prajapati (AAPS PharmSciTech, 2025)

Optimization and Evaluation of Colchicine Patch Formulation Based on Box-Behnken Design - Wenliang Dong; Jiahao Feng; Xiang Liu; Jianlu Qu; Cunhao Li; Lian Li; Shunnan Zhang; Wenlong Li (AAPS PharmSciTech, 2025)

Exploring Protein Aggregation in Biological Products: From Mechanistic Understanding to Practical Solutions - Satish Rojekar; Amol D. Gholap; Krishna Jadhav; Ganesh Shevalkar; Vrashabh V. Sugandhi; Rohan Pai; Kinjal Parikh; Mahendra Kumar Prajapati; Nimeet Desai; Lalitkumar K. Vora; Rahul G. Ingle; Keshav Raj Paudel (AAPS PharmSciTech, 2025)
Proteins are vital for the regulation of several cellular functions, including the synthesis of structural components. The change in environmental conditions will impact conformational stability and result in aggregation. Protein aggregation involves different states of proteins, like nonnative, unfolded, and native states, which make them complex processes. The proper understanding of protein aggregation pathways involving the role of thermodynamically unfavoured lag phase, soluble protofibrils triggered polymerization through an exponential phase, and depleted free monomers owing to the saturation phase resulted in the leveling off of the polymerization process. The aggregated therapeutic proteins can induce deleterious immune responses in patients, and control of the aggregation is essential for better therapeutic protein stability and targeting with the help of stable protein structures and function. Protein–protein interactions (PPIs) are important for protein stability, aggregation rate, and solubility, while advanced computational and biophysical methods have been developed to characterize therapeutic protein aggregation better. Hence, an effective strategy for controlling, monitoring, and reproducing protein aggregation propensities of the polypeptide chains is required. An in-depth understanding of protein aggregation mechanisms, characterization, and combat strategies will counter the issues of protein aggregation. It will also reduce the cost of the product, time constraints, stable & effective product availability, and potential immunogenicity. Graphical Abstract

Solid Lipid Nanoparticles: An Innovative Drug Delivery System for Enhanced Bioavailability and Targeted Therapy - Kaushal Aggarwal; Sachin Joshi; Priya Jindal; Preeti Patel; Balak Das Kurmi (AAPS PharmSciTech, 2025)

Innovative Microneedle-based Therapies for the Treatment of Diabetic Wound Healing - Sunny Rathee; Richa Dayaramani (AAPS PharmSciTech, 2025)

Novel Luteolin-Zein Nanocomposite Incorporated in Hyaluronic Acid/Sodium Alginate Scaffold as Potential Immunomodulation for Pressure Ulcer Wounds - Nouran M. Atia; Yasmine M. Shahine; Ossama Y. Abdallah; Mohamed S. Abdel Ghany; Mona A. Moustafa (AAPS PharmSciTech, 2025)
Luteolin (LUT) is a brilliant anti-inflammatory drug having a potential role in wound healing. Nevertheless, its clinical application is inadequate due to its hydrophobicity and poor skin permeation. Pressure ulcers are chronic wounds that have limited and definite treatments. This work aimed to develop a LUT-zein nanocomposite in a bioactive polymeric scaffold as a topical treatment for pressure ulcer wounds by assessing its effect on the pressure ulcers' immune microenvironment. LUT loaded scaffolds were prepared and evaluated regarding particle size, zeta potential, swelling & erosion capacity. Structure elucidation was performed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The scaffold (F6) that utilized hyaluronic acid (HA) and sodium alginate (SA) in a concentration of 4:1 revealed the most promising results and it was selected for the in vivo studies. The scaffold (F6) showed a nanosize (240.00 ± 8.54 nm) and a negative ZP (-38.2 ± 2.49 mV). SEM revealed a vastly porous structure in both cross-sections and surface views. In vivo wound healing potential and histological study were evaluated using male Sprague Dawley rats. This is the first study to design LUT-Zn nanpcomposite loaded in HA/SA scaffolds to enhance healing rate and decrease ulcer formation. The selected scaffold showed superior efficacy in modulating the immune microenvironment of the pressure ulcer wound in-vivo as it significantly inhibited IL17A secretion, upregulated IL13 and VEGF, increased miRNA-223 expression, and reduced cell apoptosis within the wound microenvironment, making it a promising treatment for chronic pressure ulcers. The elaborated F6 scaffold could be considered as a talented nanotherapy for enhanced pressure ulcer healing and wound closure rate .

Nanocubospray of Epigallocatechin Gallate for Prevention of Oral Submucous Fibrosis - Chetan Hasmukh Mehta; Varalakshmi Velagacherla; Suman Manandhar; Yogendra Nayak; Karkala Sreedhara Ranganath Pai; Shruthi Acharya; Usha Yogendra Nayak (AAPS PharmSciTech, 2025)
NanoCubes loaded film-forming spray (NanoCuboSpray) is a new formulation that can be explored for nanoscale drug delivery. In the present work, epigallocatechin 3-gallate (EGCG) was encapsulated into NanoCuboSpray (NCS) for oral submucous fibrosis (OSF) treatment. The newly formulated EGCG NCS is then evaluated for ex vivo permeation, drug retention, in vivo efficacy, and safety. The developed formulation was homogeneous, viscous, spreadable and mucoadhesive on the buccal mucosa. EGCG NCS had good permeation and buccal mucosal retention in the ex vivo studies. The NCS with 81.81 mg/kg EGCG dose significantly enhanced mouth opening and effectively upregulated collagen and downregulated TGF-β1 in rats with areca nut extract-induced OSF. EGCG NCS demonstrated better improvements in histopathological and antioxidant parameters compared to EGCG hydrogel and betamethasone injection (BTM Inj.). In the safety evaluation, NCS treatment had negligible changes in histopathological features and serum biochemical markers, maintaining results comparable to the normal control group. Therefore, the optimized NCS presents a safer alternative strategy for treating OSF and holds the potential for further evaluation of its clinical efficacy. Graphical Abstract

Gallic Acid-Loaded Transethosomal Gel for Enhanced Topical Delivery and Sustained Therapeutic Efficacy in Psoriasis Management: Formulation, Optimization, In Vitro and Ex Vivo Assessment - Tenzin Sonam Dongsar; Tenzin Tsering Dongsar; Abdulrhman Alsayari; Shadma Wahab; Garima Gupta; Prashant Kesharwani (AAPS PharmSciTech, 2025)

Retraction Note: Design, Synthesis, and In Vitro Evaluation of Low Molecular Weight Protamine (LMWP)-based Amphiphilic Conjugates as Gene Delivery Carriers - Sepideh Arabzadeh; Zeinab Amiri Tehranizadeh; Hamideh Moalemzadeh Haghighi; Fahimeh Charbgoo; Mohammad Ramezani; Fatemeh Soltani (AAPS PharmSciTech, 2025)

Innovative Antimicrobial Nanofibers: Natural Integrations for Enhanced Wound Healing and Biofilm Disruption - Eman Abdelhakeem; Heba Attia; Mona M. Hashem; Mohamed A. Abdel Khalek; Shaimaa M. Badr-Eldin; Islam M. Adel (AAPS PharmSciTech, 2025)
Wound infections caused by multidrug-resistant bacteria present a substantial challenge in healthcare. Nanofibers, particularly when infused with natural extracts, are emerging as promising platforms for antimicrobial applications. This study investigates the potential of Anastatica hierochuntica extract-loaded electrospun nanofibers prepared with thermoplastic polyurethane for combating infections and promoting wound healing. Electrospinning was utilized to prepare nanofibers infused with Anastatica hierochuntica extract, resulting in uniform rod-shaped structures confirmed by scanning electron microscopy. The hydrophilicity of the nanofibers was assessed through water contact angle (WCA) measurements and swelling tests. Mechanical properties, including strain and stress were evaluated to determine suitability for drug delivery. The formulation with optimal properties, designated as NF20, underwent further investigation. Drug release profiles were analyzed over 72 h, and antimicrobial efficacy was tested against various pathogens, with comparisons made to Silymarin as a standard. A biofilm study evaluated the anti-virulence activity, while wound healing assays assessed the optimized extract loaded nanofibers potential in fostering tissue repair. The extract-loaded nanofibers exhibited enhanced hydrophilicity, with a WCA of 43.1 ± 0.6° and swelling of 216.67 ± 2.36% after 1 h. NF20 demonstrated superior mechanical properties, with strain and stress values of 67.6% and 0.0486 N/mm 2 , respectively. The sustained release profile indicated 73.40 ± 1.31% release after 72 h. Antimicrobial tests revealed significant reductions in minimum inhibitory concentration, minimum bactericidal concentration, and minimum fungicidal concentration against key pathogens. The biofilm study confirmed extract loaded nanofiber’s efficacy in inhibiting biofilm formation and disrupting established biofilms. These findings underscore the potential of the extract-loaded nanofiber composed of thermoplastic polyurethane as innovative wound dressings that enhance antimicrobial properties, promote accelerated healing and support tissue regeneration. Graphical Abstract

Hot Melt Extruded Aceclofenac-Soluplus® Solid Dispersion: Mechanistic View of Miscibility and Drug-Carrier Interactions for Enhanced Dissolution - Likhitha U; Roushan Bharti; Reema Narayan; Chetan H. Mehta; Usha Yogendra Nayak (AAPS PharmSciTech, 2025)
Aceclofenac (ACF), a Non-Steroidal Anti-Inflammatory Drug (NSAID), is formulated with Soluplus® (SOLP) to enhance solubility and bioavailability. This study presents a distinct approach by utilizing Hot Melt Extrusion (HME) to prepare Aceclofenac-Soluplus® solid dispersion (ACF-SOLP), in contrast to the previously investigated nanoemulsion technique. The HME technique facilitates a uniform drug distribution within the polymer matrix, increasing ACF's dissolution rate. Different weight ratios of ACF and SOLP were assessed with 1:8 (HM4), which proved to be the optimal choice. ACF is dispersed within SOLP in its amorphous state, and HM4 exhibited a significant increase in drug release as compared to pure ACF and its physical mixture. I n vivo pharmacokinetic data of HM4 demonstrated a drastic improvement in the C max (7.1 ± 0.14 µg/ml) and AUC (12.1 ± 1.30 µg-h/ml). Further, molecular dynamics simulation revealed that the polymer is widely dispersed within the supramolecular architecture of ACF-SOLP, with ACF positioned centrally, confirming the favorable interactions between the components. Leveraging the hydrophilic nature of the SOLP, the solid dispersion demonstrated enhanced dissolution of ACF, while HME synergistically reinforced the combination. This approach presents a compelling alternative to traditional methods, unlocking new possibilities for formulating poorly soluble drugs. Graphical Abstract

Recent Advances in the Local Drug Delivery Systems for Diabetic Wound Healing: A Comprehensive Review - Reem Khaled Wassif; Rehab Nabil Shamma; Nada M. El-Hoffy; Maha El-Kayal (AAPS PharmSciTech, 2025)
Wound management in diabetic patients holds significant importance in both clinical and social contexts due to the delayed and compromised healing that these individuals experience. Diabetic wounds exhibit slow and incomplete healing, increasing patients’ susceptibility to infections. Managing wounds in diabetic patients, particularly when complicated by diabetic foot infection or diabetic foot ulcer, becomes challenging. The ideal drug delivery systems for treating diabetic wounds should integrate diverse drugs and/or biological factors, offering advantages such as sustained and localized release of therapeutic compounds and enhanced wound healing outcomes. Several treatment modalities are under investigation for managing diabetic wounds, including advanced local drug delivery systems such as topical 3D scaffolds, particulate systems, and 3D scaffolds combined with particulate systems, in addition to gas therapy and skin grafts as advanced therapies. This review comprehensively discusses the state of the art for each treatment modality for diabetic wound healing associated with bioactive molecules. It also summarizes the forms of topically applied 3D scaffolds, including films, hydrogels, sponges, nanofibers, wafers, microneedles, and foams. The review differentiates their advantages and disadvantages as topical therapies while discussing various scaffold types that integrate therapeutic agents, which include polymeric, inorganic, composite, and biological scaffolds. With the emphasis on the newly investigated locally administered drug delivery systems for the management of diabetic wounds, the review also focuses on the challenges and the future perspectives for the production of such systems with the use of various drugs and biomaterials using innovative technologies such as 3D printing for effective healing of wounds. Graphical Abstract

Intranasal Delivery: Formulation Factors and Insights Into User Experience - Shabbir Lobo; Zhangjie Xi; Debanjan Das; Norell M. Hadzimichalis; John A. Creek (AAPS PharmSciTech, 2025)
Improving nasal spray use experience is typically not addressed as a key product requirement even though sensations of bitterness, sourness, astringency, or burning after intranasal application can cause significant repulsion, consumer non-compliance from recommended usage and product rejection. Extensive studies have been carried out by academia and industry alike into the formulation characteristics of sprays and consumer preferences to make nasal sprays more “acceptable” by patients. Due to lack of a collative synopsis of these works, this review article attempts to gather and summarize these studies, address the various attributes that impact post spray experience, and provide suggestions towards maximizing user compliance. We systematically categorized a range of factors which can contribute to unpleasant experiences using nasal sprays including anatomical characteristics of the nose, formulation and device properties, formulation components and dosages, etc. Furthermore, we collated relevant information from pharmaceutical and non-pharmaceutical domains to create a comprehensive knowledge base to frame the scope of the issue. Unpleasant sensorial attributes can be controlled by designing the formulation with a thorough understanding of product-device interactions and novel use of excipients. By choosing excipients such as taste masking agents, flavors, and novel polymers the behavior of the product in the nasal canal can be modulated to block the burning, astringent or bitterness sensation on spray use. This paper discusses these factors in comprehensive detail while offering solutions to ensure a superior product experience. The paper also discusses challenges to adoption and compliance strategies of some newer techniques and excipients. Graphical Abstract

Topical Foam for Simultaneous Treatment and Decontamination of Chemical Warfare Agents on Dermal Exposure - Sonalika Arup Bhattaccharjee; Mohammad Shajid Ashraf Junaid; Meheli Ghosh; Ritesh Srivastava; Mohammad Athar; Ajay K. Banga (AAPS PharmSciTech, 2025)
Being highly toxic and a quick-acting vesicant, even small amounts of lewisite if not decontaminated immediately are rapidly absorbed into systemic circulation via skin exposure, leading to acute poisoning and death. The skin is the first major target to such chemical weapons. Although the stratum corneum provides a barrier lewisite being a lipophilic molecule that readily permeates this barrier. This necessitates, making early and thorough decontamination prior to manifestation of adverse effects. For this, we aimed to decontaminate skin using an antidote-loaded topical foam, followed by treating local and systemic toxicity using the same formulation. Successful incorporation of 1% antidote into a decontaminating topical foam and the delivery of 1.78 ± 0.21 µg/sq cm into dermatomed porcine ear skin within five minutes of application was achieved. Decontamination after five minutes of exposure (88.43%), as well as prolonged exposure (94.53%; 3 h) to methyl salicylate, a warfare chemical simulant, was demonstrated. The developed formulation demonstrated the potential to back-extract simulant from skin tissue but could not purge simulant penetrated systemic circulation. However, systemic delivery of the antidote was demonstrated, establishing the potential to treat the toxicity caused by the remnant warfare chemicals. Graphical Abstract

Intranasal Delivery of Cetrorelix Via Lipid Liquid Crystal Nanoparticles: Characterization and Pharmacokinetic Studies in Rats - Soheil Tafazzoli Mehrjardi; Mohsen Tafaghodi; Saba Malek; Davood Yari; Amir Hooshang Mohammadpour; Hossein Kamali; Ali Nokhodchi (AAPS PharmSciTech, 2025)
Nasal sprays are extensively researched due to their rapid absorption, high bioavailability, and low side effects. Lipid liquid crystal nanoparticles (LLCNs) are being considered as potential carriers for intranasal delivery. LLCs loaded with cetrorelix (GnRH antagonist) were utilized for intranasal drug delivery to enhance brain targeting while minimizing systemic exposure. A single-phase formulation incorporating HPMC as a mucoadhesive was developed to extend nasal residence time. Following intranasal administration of cetrorelix in rats, its distribution in various brain regions and serum was assessed using LC–MS-MS. In the LLC formulation, the particle diameter, PDI, and Zeta potential were measured as 204.92 ± 0.89 nm, 0.188 ± 0.019, and -21.63 ± 1.72 mV, respectively. A monomodal distribution and low polydispersity index were observed, along with a negative zeta potential. Cetrorelix was released from the LLC in a biphasic profile, with an initial burst release of 30%, followed by a gradual and sustained release phase. The LLCs containing cetrorelix exhibited lower cytotoxicity compared to the LLC base. The nasal administration of cetrorelix via LLCs presents a promising advancement for nose-to-brain drug transport. The pharmacokinetic data demonstrated that the AUC 0-360min for brain tissue analysis, following nasal administration of the single-phase formulation, was 3.104 ng/ml.min. The value was 7.104 ng/ml.min for LLC nasal administration and 6.104 ng/ml.min for subcutaneous injection. The maximum concentration (C max ) values for brain tissue analysis indicated a significant increase with LLC nasal administration (238 ± 6. 2 ng/ml) in comparison to the single-phase formulation (202.5 ± 6.3 ng/ml) and subcutaneous injection (218.2 ± 3. 1 ng/ml). In serum analysis, the C max values were significantly elevated, with subcutaneous injection achieving (4983.3 ± 2.5 ng/ml), followed by LLC nasal administration at (93.1 ± 6.2 ng/ml), and the single-phase formulation at (43.7 ± 2.2 ng/ml). This innovative method aims to target the brain directly, eliminating the need for needles, and reducing adverse effects, hence offering new hope for brain-targeted drug delivery. This study introduces, for the first time, a cetrorelix-loaded lipid liquid crystal (LLC) nanoparticle formulation for intranasal nose-to-brain delivery. The LLC system achieved enhanced brain targeting efficiency while reducing systemic exposure compared to conventional subcutaneous injections and simple nasal formulations, representing a promising advancement in GnRH drug delivery strategies. Graphical Abstract

Formulation Development and Characterization of Bigels Containing Curcumin for Topical Skin Delivery - Lord Sam Liston; Suranate Phanapithakkun; Nuttakul Pimsarn; Nuttapon Dangkaokhia; Thanat Nakasan; Attawadee Sae Yoon; Hiroaki Todo; Teerapol Srichana; Somchai Sawatdee; Gerard Lee See; Florencio Arce; Pajaree Sakdiset (AAPS PharmSciTech, 2025)

Co-delivery of Exemestane and Genistein via Chitosan Coated Liposomes for Enhanced Antitumor Effect and Bone Loss Prevention in Breast Cancer Therapy: In Vivo Evaluation - Shwetakshi Sharma; S. M. Kawish; Priya Gupta; Shreshta Jain; Shahnawaz Ahmad; Zeenat Iqbal; Divya Vohora; Kanchan Kohli (AAPS PharmSciTech, 2025)

Phospholipid Complex-based Topical Gel for Codelivery of Erlotinib and Methotrexate in Psoriasis - Sanyog Jain; Shivani Mali; Junia Akhtar; Chander Parkash Dora; Rahul R. Mahajan (AAPS PharmSciTech, 2025)

Design of Passion Fruit Oil Emulgel for Topical Chrysin Delivery and Ex Vivo Evaluation of Skin Permeation by Photoacoustic Spectroscopy - Bruna Gheller de Souza; Lidiane Vizioli de Castro Hoshino; Thalita Schilive Faccin; Mauro Luciano Baesso; Fernanda Belincanta Borghi-Pangoni; Marcos Luciano Bruschi (AAPS PharmSciTech, 2025)

Development and In Vitro Characterization of Azithromycin-PLGA Nanoparticles Loaded Thermoresponsive Hydrogels: A Quality by Design Approach Toward Intra-Articular Delivery of Macrolides - Bao Ngoc Tran; Cam Le Ha; Duyen Thi Thuy Vu; Chien Ngoc Nguyen (AAPS PharmSciTech, 2025)

Optimizing Extended-release Formulation of l-tetrahydropalmatine Based on In Vivo Outcomes Using Integrated Modeling Approaches - Thi-Phuong-Dung Pham; Huy Minh Dao; Nguyen-My-Linh Pham; Thanh-Vinh Dang; Hoang-Anh Nguyen; Cao-Son Tran; Linh Nguyen Tran; Nguyen-Thach Tung (AAPS PharmSciTech, 2025)

Development, Characterization, and Molecular Dynamics Simulation of Andrographolide Nanosuspensions Utilizing Hummer Acoustic Resonance Technology - Li Wang; Xiaoyang Zhang; Jianlu Qu; Zhanrui Zhang; Wei Wu; Wenlong Li (AAPS PharmSciTech, 2025)

Taste Masking of Primaquine Phosphate: A Comparative Evaluation of Three Taste Masking Agents - Galande Ankit; Gagare Tejashree; Sahu Surbhi; Kulkarni Madhur (AAPS PharmSciTech, 2025)

Unveiling the Potential of Nanoclays in Pharmaceuticals - Rabab Kamel; Giuseppina Nocca; Elena Mazzinelli; Somaia S. Abd El-Karim; Valerio Papa; Ilaria Cacciotti; Nermeen A. Elkasabgy (AAPS PharmSciTech, 2025)
Clay minerals or nanoclays are layered aluminosilicate nanoparticles with unique physicochemical properties, excellent biocompatibility, high surface area, lamellar structure, diverse ion-exchange capacity, tuneable surface chemistry enabling them to form different intermolecular interactions which offer supreme prospects for optimized pharmaceutical applications. This review article dives into the key characteristics of different types of nanoclays like Halloysite, Kaolinite, Sepiolite, Montmorillonite, Bentonite and Laponite, highlighting their possible exploitation within the pharmaceutical landscape. Also, the review describes the recent advances in nanoclay-based drug delivery systems and discusses the role of nanoclays as drug carriers and their use in tissue engineering and gene therapy. Nanoclays, are used to modulate drug release and stabilize the loaded active molecules as well as to enhance drug loading. Interdisciplinary research, advanced characterization techniques, and careful formulation designs are required to augment the use of nanoclays in various pharmaceutical applications. Despite the faced challenges, research on nanoclay-based drug delivery systems is growing. With targeted research and development, nanoclays are poised to redefine the biomedical domain, offering tailored and efficient therapies for a multitude of diseases. Graphical Abstract

Development and Evaluation of Huperzine A-Loaded Microneedles for Transdermal Delivery and Pretreatment of GD Poisoning - Guixiang Yang; Yi Zhang; Chong Li; Xingle Xia; Qian Jin; Liqin Li; Xingxing Zong; Dongxin Liu; Jingchen Wei; Xuejun Chen; Chen Wang (AAPS PharmSciTech, 2025)

Skin can Modulate the pH of Topical Creams and Gels - Sanjeevini M; Harini Priya Pa; Rakshitha L; Prajwal N. Murthy; Pragathi S. G; Anusha V. Matadh; Srujana N. Murthy; Srinath R; Shivakumar H. N; Howard Maibach; S. Narasimha Murthy (AAPS PharmSciTech, 2025)

Nanosizing and Surface Modification by Propellant Assisted Aerosolization Enhances Solubility and Dissolution of Estradiol - Gaurav K. Jain; Gaurav Chaudhary; Mohammad Akhlaquer Rahman; Musarrat Husain Warsi; Mohammad Imran (AAPS PharmSciTech, 2025)

Application of Physiologically Based Biopharmaceutics Modeling (PBBM) to Establish Clinically Relevant Dissolution Specifications for a Prolonged Release Tablet Formulation of Verapamil, a BCS Class I Drug - Anagha Damre; Aniruddha Banerjee (AAPS PharmSciTech, 2025)

Degradable Hydrogel Microspheres for Drug Delivery: In Vitro Performance and Influence of E-Beam Sterilization - Laurent Bédouet; Anne Beilvert; Emeline Servais; Laurence Moine (AAPS PharmSciTech, 2025)
The present work examines the in vitro drug delivery performance of degradable microspheres (DrugMic) composed of a crosslinked hydrogel of poly(ethylene glycol), with particular interest on the effect of e-beam sterilization on the stability of loaded active substances , i.e. niflumic acid (14% w/w), tadalafil (7% w/w), travoprost (0.2% w/w), buprenorphine (1.4% w/w), teicoplanin (6% w/w), and polymyxin B (5.6% w/w). Drug loading was performed on preformed microspheres degradable in 3 days, 1 or 2 weeks. Drugs were loaded onto microspheres (50–100 µm or 500–700 µm) via 1 h room-temperature incubation. After freeze-drying, drug-loaded microspheres were sterilized using e-beam irradiation (15 or 25 kGy). In vitro drug releases were done in PBS, drug elution profiles and radiostability were assessed by RP-HPLC with diode array detection. Following irradiation, DrugMic delivered niflumic acid and tadalafil for 3 days, teicoplanin and polymyxin B for 1 week, buprenorphine and travoprost for 2 weeks from microspheres degradable in 3 days, 1 and 2 weeks. Radiolysis was observed in each fraction collected during buprenorphine (0.7–20%) and travoprost (1.8–139%) release, while the HPLC profiles of polymyxin B were completely altered, indicating substantial degradation. Niflumic acid, tadalafil and teicoplanin showed no signs of radiolysis. Extemporaneous loading of buprenorphine and polymyxin B onto sterilized microspheres was attempted to avoid radiolysis. The sustained release profiles were maintained without degrading the drug. DrugMic appears to be a suitable platform for sustained drug release. The loading mode can be adapted according to the stability of the drug to irradiation. Graphical Abstract

Correction: Laser-mediated Solutions: Breaking Barriers in Transdermal Drug Delivery - Ehsan Haghsay Khashechi; Abolfazl Afaghmehr; Niloofar Heidarizade; Ashkan Barfar; Javad Shokri (AAPS PharmSciTech, 2025)

Nanocarrier-based Drug Delivery Systems to Enhance Antimicrobial Photodynamic Therapy in Dental Applications: A Review - Negar Ebrahimi; Alireza Ranjbar; Sima Shahabi; Shima Afrasiabi (AAPS PharmSciTech, 2025)

Freeze-Drying as a Tool for Preparing Porous Materials: From Proof of Concept to Recent Pharmaceutical Applications - Kawthar K. Abla; Mohammed M. Mehanna (AAPS PharmSciTech, 2025)

Preparation and Characterization of Diclofenac Sodium-Purolite A430MR Complexes for Taste Masking - Genyang Ye; Qun Wang; Yibo Shang; Yibo Li; Rui Yang; Boyu Jing; Qiang Fu (AAPS PharmSciTech, 2025)

Recent Advances in Development of Buccal Formulations: From Small to Macromolecules - Vrundakumari R. Solanki; Vijaykumar K. Parmar (AAPS PharmSciTech, 2025)

Sublingual Delivery of Human GLP-1 Loaded Nanoliposomal Hydrogel for Treatment of Type 2 Diabetes Mellitus - Shivani Khopade; Tejas Girish Agnihotri; Shraddha Baviskar; Bhaskar Pavar; Shyam Sudhakar Gomte; Tejas Maskar; Nitish Sharma; Hemant Kumar; Santosh Kumar Behera; Aakanchha Jain (AAPS PharmSciTech, 2025)

Advances in Characterization of Transdermal and Topical Products using Texture Analyzer Systems - Khadeejeh AL-Smadi; Masood Ali; Jiexin Zhu; Ayyah Abdoh; Khanh Phan; Yousuf Mohammed (AAPS PharmSciTech, 2025)
The efficacy, safety, and stability of transdermal and topical products (TTPs) are of prime importance to consumer acceptance and compliance. To control the consistent textural quality or overall physical properties of TTPs, texture analysis tests are widely applied to assess potential changes in features and internal structure of products throughout different stages of formulation development, manufacturing, and distribution. As one of the essential texture test types, Texture Profile Analysis (TPA) provides critical insights into the structure, spreadability, adhesion, sensory attributes, and consistency of semisolid formulations via key measured parameters such as hardness, adhesiveness, cohesiveness, elasticity, and compressibility. Recent advancements in automation and multimodal analysis have enhanced the precision and applicability of TPA. For transdermal delivery systems (TDS), adhesion, a critical quality attribute (CQA), which is influenced by viscoelasticity, surface energy, and wetting characteristics of pressure-sensitive adhesives (PSAs), can be assessed through in vitro methods like peel, tack, and shear tests using texture analyzer systems. While in vivo assessments remain subjective, in vitro tests conducted by texture analyzers enable standardized and reproducible evaluations, ensuring reliable comparisons across products and bridging gaps between laboratory and real-world performance. Microneedles (µNDs), another innovative transdermal platform, require robust mechanical strength to ensure effective skin penetration and drug release. Texture analysis plays a pivotal role in characterizing critical properties such as hardness, flexibility, and puncture strength, simulating forces encountered during skin penetration. This analysis offers valuable insights into µND performance, ensuring safety, functionality, and patient compliance. This review systematically curates existing knowledge on using texture analyzers to measure textural properties of pharmaceutical TTPs while highlighting emerging trends and providing methodologies for testing and parameter derivation. By emphasizing the importance of CQA characterization for novel drug delivery platforms, this work underscores the role of texture analysis in optimizing designs of TTPs including µND, focusing on fracture, insertion, and bending forces, ultimately contributing to the development of safer and more efficient transdermal systems. Graphical Abstract

Injectable PLGA-based In Situ Forming Subconjunctival Implant for Sustained Ocular Delivery of Ketotifen Fumarate: Formulation, Drug Release, and Biocompatibility Studies - Nur Mita; Xuejia Kang; Pengyu Chen; Oladiran Fasina; Shenise Howard; Anna-Catherine Bowden; Richard J. McMullen; Amol Suryawanshi; R. Jayachandra Babu (AAPS PharmSciTech, 2025)
Ketotifen fumarate is very effective in treating ocular conditions like allergic conjunctivitis. However, its clinical effectiveness is limited by rapid washout, frequent dosing, and poor bioavailability. This study developed a ketotifen fumarate -loaded in situ forming subconjunctival injectable implant ( ISFSI ) for use in large animal species such as horses and alpacas. ISFSIs were formulated by dispersing ketotifen fumarate in polylactide-co-glycolide ( PLGA ) combined with different release retarders ( Kolliphor ® RH 40, Labrasol ® , and Maisine ®) , then characterized for visual appearance, viscosity, solidification time, and in vitro drug release. The changes in the release medium pH and the solidified ISFSI wet weight were monitored for up to 4 weeks. The selected ISFSI , KFM5, was further characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and rheological behavior. The injectability of KFM5 was predicted using the power law for five different syringe and needle dimensions. Cytotoxicity was tested using the Alamar Blue assay and Calcein AM/PI staining on a human corneal epithelial cell line (HCE-T). Results showed that all ISFSI formulations were clear yellowish, with drug recoveries exceeding 95%, varying viscosities, and solidified upon contact with the release medium. KFM5 exhibited a triphasic drug release profile with the lowest burst release (4.91 ± 0.55%) and followed Higuchi kinetics. SEM imaging revealed a "hollow and sponge-like" structure, while DSC confirmed the crystallinity and thermal transitions of ketotifen fumarate within the solidified implant. Rheological analysis indicated shear-thinning fluid behavior with acceptable injection forces. Cytotoxicity assays confirmed > 90% cell viability, confirming biocompatibility in the ocular tissue. Graphical Abstract

The Role of Low Global Warming Potential Propellants on Suspension Metered Dose Inhaler Sprays - Daniel J. Duke; Lingzhe Rao; Benjamin Myatt; Phil Cocks; Stephen Stein; Hui Xin Ong; Paul Young (AAPS PharmSciTech, 2025)
The reformulation of suspension-based pressurized metered dose inhalers (pMDI) with low global warming potential (GWP) propellants is challenged by wide-ranging changes to their chemicophysical properties such as vapor pressure, density and latent heat. The effect of low-GWP propellants on spray pattern and plume geometry for suspension pMDIs are not fully understood. There is a lack of data regarding the role of propellant choice and potential interactions with suspended drugs, which may explain performance variations between products and guide development of in-silico models. In this study, high speed imaging was used to measure the plume morphology and optical density of sprays containing HFA134a, HFA152a and HFO1234ze(E) propellants. Propellant-only placebo controls were compared to suspension formulations containing 2 mg/mL salbutamol sulphate. It was found that the presence of suspended particles has a significant effect on plume structure, reducing correlations between propellant thermophysical properties and cone angle, targeting angle, and optical center of mass by 6–7 times. These effects vary depending on propellant type due to variations in flash-evaporation behavior, which is less pronounced in low-GWP propellants compared to HFA134a. HFA152a sprays have a 23% reduction in Jakob number compared to HFA134a; plume width at the mouthpiece exit is commensurately increased by 40%. Equivalent HFO1234ze(E) sprays have less pronounced differences in Jakob number (13% reduced) and plume width (25% increased) compared to equivalent HFA134a sprays. Empirical models and standards which implicitly incorporate the flash-evaporation effects commonly observed in high-GWP HFA propellants may require adjustment to be suitable for use with low-GWP formulations. Graphical Abstract

Antitumor Efficacy of Paclitaxel Injection Concentrate for Nanodispersion in Patient-Derived Breast, Head and Neck, and Non-Small Cell Lung Cancer Mouse Xenografts - Ajay J. Khopade; Malay D. Shah; Bhushan S. Borole; Vinod Burade (AAPS PharmSciTech, 2025)

Combination Drug Product of Amorphous Solid Dispersion Show Extended Supersaturation and Enhanced Dissolution - Prachi Joshi; Abhay T. Sangamwar (AAPS PharmSciTech, 2025)

Preparation and Study of Erythromycin Dry Powder Inhaler Based on Ternary Complex Structure - Hongyu Yang; Jianpeng Qin; Yuou Wang; Ji Li; Dongkai Wang (AAPS PharmSciTech, 2025)

Grape Seed Oil Microemulsion for Improved Skin Delivery of Resveratrol - Marianne A. P. C. Nogueira; Camila O. Cardoso; Lucas F. F. Albuquerque; Marcilio Cunha-Filho; Tais Gratieri; Guilherme M. Gelfuso (AAPS PharmSciTech, 2025)

Correction: Stability Evaluation of Lyotropic Liquid Crystalline Precursor for the Co-delivery of Chlorhexidine and Silver Nanoparticles - Fangqin Fu; Xin Li; Tengyi Zheng; Xiao Xia; Minqun Du; Zhengwei Huang; Ying Huang; Xin Pan; Chuanbin Wu (AAPS PharmSciTech, 2025)

Optimizing In Vitro Skin Permeation Studies to Obtain Meaningful Data in Topical and Transdermal Drug Delivery - Rajesh Sreedharan Nair; Nashiru Billa; Andrew P. Morris (AAPS PharmSciTech, 2025)
Drug delivery through the skin provides several advantages over other administration routes, including the avoidance of first-pass metabolism and gastrointestinal side effects, prolonged drug release, and significant improvement in patient compliance. It is imperative to study the in vitro behavior of drugs and formulations before proceeding to in vivo evaluations. As the ethical guidelines for scientific research evolve, there is an increasing emphasis on adopting alternative methods to reduce animal use. An in vitro permeation study (IVPT) estimates the rate and extent of drug permeation from a topical or transdermal delivery, determining its availability at the skin layers or into the systemic circulation. Vertical Franz diffusion cells are commonly employed for IVPT studies to evaluate the permeation of drugs across skin or other biorelevant membranes. This comprehensive review provides a clear understanding of the importance of optimizing in vitro experimental conditions to obtain reliable and reproducible data. We discuss various in vitro skin models, including excised human and animal skins, human skin equivalents (HSEs), synthetic membranes, and 3D-printed skin models. Additionally, a broad overview of setting up in vitro diffusion cells is provided. Emphasis is given on donor phase design, receptor medium selection, the importance of solubility and stability studies, sampling techniques, and analysis methods. Meticulous design and optimization of in vitro permeation experiments are crucial for generating reproducible data, which are essential for predicting the dermatokinetics of drugs and formulations. Graphical Abstract

Mitigating Shear Stress in Spray Drying for RNA-Loaded Lipid Nanoparticles through Process and Formulation Optimization - Susana Farinha; Rute Mota; Carolina Lopes; Ricardo Velez; Mara G. Freire; Ana Aguiar-Ricardo; Miguel Ângelo Rodrigues; Luís Marques; Joana S. Cristóvão; Paulo Roque Lino (AAPS PharmSciTech, 2025)

Microneedle Innovations in Oral Therapeutics: Transforming Protein and Peptide Delivery - Kirthana Gopal; Syed Mahmood; Zarif Mohamed Sofian; Ayah R. Hilles; Najihah Mohd Hashim (AAPS PharmSciTech, 2025)

Printabily of Pharmaceutical-Grade Polymers using Selective Laser Sintering with a CO2 Laser - Atabak Tabriz; Laura Andrade Junqueira; Siva Satyanarayana Kolipaka; Ho-Wah Hui; Nathan Boersen; Sandra Roberts; John Jones; Dennis Douroumis (AAPS PharmSciTech, 2025)
Selective laser sintering (SLS) has gained attention for pharmaceutical applications and the printing of solid oral dosage forms. The aim of this study was to evaluate the suitability of various pharmaceutical-grade polymers for tablet production using an SLS printer equipped with a CO 2 laser. Seven polymers, offering a range of release profiles such as immediate, controlled, and pH-dependent, were selected for investigation. Initially, the materials were characterized, revealing significant variations in their properties, including glass transition temperature, degradation temperature, mean particle size, and flowability. While some polymers exhibited ideal properties for printing, others were less suitable. By varying printing parameters such as the laser power, bed temperature, scanning speed, and powder feed rate, all powders were used for the reproducible fabrication of tablets. The physical properties of the tablets, including the hardness and friability, as well as their microstructure were affected by both the polymer grade and the laser intensity. The tablet physical characteristics varied according to the used polymer and thus hardness values ranged from 31 to 350 N, while friability varied across different formulations, with few tablets exhibiting values below 1%, others between 1–3%, and some exceeding 5%. Overall, this work demonstrated the suitability of using various pharmaceutical-grade polymers to produce tablets using SLS with a CO 2 laser. Graphical Abstract

Tablet Color Changes Due to Light Irradiation and Titanium Dioxide: Color Change Prevention Using Plasticizers - Yuki Matsushima; Reo Kainuma; Hidemasa Katsumi; Akiko Tanaka; Tomoyuki Furubayashi; Toshiyasu Sakane (AAPS PharmSciTech, 2025)

In Vitro and In Vivo Appraisal of Glycerylmonostearate/chitosan Hybrid Nanocapsules As Peroral Delivery System of Simvastatin - Mohammed Elmowafy; Khaled Shalaby; Nabil K. Alruwaili; Omar Awad Alsaidan; Mohammed H. Elkomy; Mohamed A. Abdelgawad; Ehab M. Mostafa; Ayman Salama; Abdulsalam M. Kassem; Mohamed F. Ibrahim; Mahran Mohamed Abd El-Emam (AAPS PharmSciTech, 2025)

Fabrication of 3D Printed Microneedle Patch for the Simultaneous Delivery and Detection of Melatonin from Interstitial Fluid - Shreya Chauhan; Venkata Vamsi Krishna Venuganti (AAPS PharmSciTech, 2025)

Formulation and In-Vitro Testing of Nebulized Camostat Mesylate Loaded Nanoliposomes for the Treatment of SARS-CoV- 2 Infection - Rama Kashikar; Arun Kumar Kotha; Rakshya Shrestha; Rudragouda Channappanavar; Mahavir Bhupal Chougule (AAPS PharmSciTech, 2025)
COVID- 19, caused by the coronavirus SARS-CoV- 2, has arisen as a global health epidemic, claiming the lives of millions of people throughout the world. Combating the pandemic has involved developing and approving vaccines and antiviral products. Camostat Mesylate (Camo) is a TMPRSS2 inhibitor that inhibits virus-cell membrane fusion and, thereby, viral multiplication. Significant limitations of using oral Camo include the limited amount of Camo reaching the site of action, lungs, side effects due to distribution to all tissues, and enzymatic breakdown in the gut. This investigation aims to develop self-administrable and patient-compliant extended-release Camo-loaded pegylated nanoliposomes (Camo-pegNLs) for delivering Camo directly to the lungs, thereby enabling faster onset of action and overcoming limitations of oral Camo delivery. We developed the Camo-pegNLs were composed of 1,2-dipalmitoyl-sn-glycerol- 3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycerol- 3-phosphoethanolamine (DOPE-PEG, MW2000) and cholesterol using the ethanol injection technique and syringe pump. The NLs were characterized for their particle size, polydispersity index (PDI), and zeta potential using Malvern Zetasizer. The assay, unentrapped Camo using Vivaspin 500 ultrafilter (10 kDa) and in-vitro release were determined. The Camo content was analyzed using a validated HPLC method. The aerodynamic properties of Camo-pegNLs were determined using a Westech Andersen Cascade Impactor (ACI) at 28.3L/min and a pneumatic jet nebulizer. The antiviral effect of Camo-pegNLs was assessed in Vero cells expressing TMPRSS2 and infected with SARS-CoV- 2. Camo-pegNLs suspension showed size of 167.50 ± 0.90 nm, zeta potential of 0.48 ± 0.04 mV, and PDI of 0.07 ± 0.01. The quantity of entrapped Camo was found to be 44.86 ± 1.35%w/v, and the drug loading was 27.41 ± 0.04%w/w. The Camo-pegNL- 2 had an extended release of up to 24 h, MMAD of 4.295 ± 0.1 µm, GSD of 1.915 ± 0.064, and FPF of 42.01% ± 6.90. Camo-pegNLs showed a significant antiviral effect on Vero cells compared to no treatment group ( p Graphical Abstract SARS-CoV- 2

Cyclodextrin-Based Inclusion Complexes Improve the In Vitro Solubility and Pharmacokinetics of Ivacaftor Following Oral Administration in Mice - David S. Nakhla; Youssef W. Naguib; Sanjib Saha; Dylan Gao; Nikesh Gupta; Walla Malkawi; Timothy M. Acri; Aliasger K. Salem (AAPS PharmSciTech, 2025)
Cystic fibrosis is a serious life-threatening hereditary disease that occurs due to a mutation in the cystic fibrosis transmembrane conductance regulator gene ( CFTR ). Ivacaftor (IVA) is a drug that targets the mutated CFTR protein. IVA is highly hydrophobic (log P = 5.6) with poor aqueous solubility (0.05 µg/mL) and is formulated as an amorphous solid dispersion tablet under the brand name Kalydeco ® . The recommended daily dose of Kalydeco ® is twice per day with a high fat meal to aid in IVA’s absorption. In this research, we studied the application of cyclodextrins (CDs) to improve the dissolution of IVA. Phase solubility studies between IVA and four different CDs (α-, β-, γ-, and hydroxypropyl-β-CD [HP-β-CD]) were conducted and a significant improvement in IVA’s aqueous solubility with HP-β-CD was observed. Solid state characterizations confirmed the formation of IVA/HP-β-CD inclusion complexes. In vitro dissolution studies were conducted at pH = 6.8 and showed improvement in IVA’s rate and extent of dissolution with IVA/HP-β-CD (1:2) complexes in comparison to uncomplexed IVA. In vivo pharmacokinetics in mice showed a 2-fold increase in area under the curve (AUC) after the oral administration of the IVA/HP-β-CD complex in comparison to Kalydeco tablets. In addition, HP-β-CD extended the release of IVA from the IVA/HP-β-CD complexes with a longer T max of 7.05 h compared to 2.96 h with Kalydeco ® tablets. These results demonstrate that CD inclusion complexes of IVA using HP-β-CD can be a successful alternative approach to improving the solubility of IVA while extending its release. Graphical Abstract

Nano-Engineered Epigallocatechin Gallate (EGCG) Delivery Systems: Overcoming Bioavailability Barriers to Unlock Clinical Potential in Cancer Therapy - Mohammad Qutub; Ujban Md Hussain; Amol Tatode; Tanvi Premchandani; Rahmuddin Khan; Milind Umekar; Jayshree Taksande; Priyanka Singanwad (AAPS PharmSciTech, 2025)

Assessment of Emergency Spacers Versus Traditional Spacers, An In-Vitro Model for Aerosol Delivery - Omar Ahmed Sayed; Mohamed E. A. Abdelrahim; Nabila Ibrahim Laz; Haitham Saeed (AAPS PharmSciTech, 2025)
Spacers, when used with pressurized metered dose inhalers (pMDIs), enhance aerosol drug delivery and address coordination challenges during inhalation. This study aimed to compare the efficacy of emergency spacers with traditional spacers in delivering salbutamol aerosol from pMDIs. The total emitted dose (TED) and particle size distribution of salbutamol were determined using an Andersen MKII cascade impactor. The study evaluated pMDI alone and with various spacers, including traditional antistatic spacers (Able, Tips-Haler, Aerochamber Plus Flow Vu, Atomizer Chamber) and emergency spacers (Plastic juice cup, MDI PLUS, Lite-Air spacer, DispozABLE spacer, and Paper sheet spacer) at a flow rate of 28.3 L/min with inhalation volumes of 2 L and 4 L, representing children (> 6 years) and adults, respectively. The pMDI alone delivered the highest TED, significantly exceeding all pMDI-spacer combinations at both inhalation volumes ( P P Graphical Abstract

Development and Evaluation of Cyclosporine a Mixed Micelle Eye Drops for Enhanced Ocular Drug Delivery - Yue Hu; Jiong Wu; Xiaoyan Du; Yan Shen; Daquan Chen; Xiujuan Feng; Dilei Yan (AAPS PharmSciTech, 2025)

Nano-Engineered Hybridized Polymeric Framework for Chronic Wound Management - Anbuthiruselvan Solaimuthu; Padmaja Murali; Ane Nishitha Vijayan; Purna Sai Korrapati (AAPS PharmSciTech, 2025)

Development and Preclinical Testing of a Rapid, High-Volume, Auto-Injector for Subcutaneous Administration with Recombinant Human Hyaluronidase - Robert J. Connor; Tara Nekoroski; David W. Kang (AAPS PharmSciTech, 2025)
Handheld auto-injectors (AIs) provide a convenient method for subcutaneous (SC) administration of therapeutics in clinical settings or at home via a caregiver or self-administration. However, AIs have been limited to low volumes ( Graphical Abstract

Development and Optimization of Stimuli-Responsive Fenugreek/Carrageenan-Co-poly (Methacrylate) Hydrogel Matrices for Controlled Delivery of 5-Fluorouracil - Muhammad Arslan; Muhammad Umer Ashraf; Ayman M. Al-Qaaneh; Aysha Aslam; Asif Mahmood; Hira Ijaz; Rai Muhammad Sarfraz; Mohamed M. Salem; Milad A. Mezher; Mounir M. Bekhit (AAPS PharmSciTech, 2025)

The Role of Artificial Intelligence in Drug Discovery and Pharmaceutical Development: A Paradigm Shift in the History of Pharmaceutical Industries - Nithin Vidiyala; Pavani Sunkishala; Prashanth Parupathi; Dinesh Nyavanandi (AAPS PharmSciTech, 2025)

Dasatinib Pharmacokinetics and Advanced Nanocarrier Strategies: from Systemic Limitations to Targeted Success - Mahesha Keerikkadu; Pragathi Devanand Bangera; Vamshi Krishna Tippavajhala; Mahalaxmi Rathnanand (AAPS PharmSciTech, 2025)
Dasatinib (DSB) is a second-generation tyrosine kinase inhibitor widely used for treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Though clinically effective, DSB has some pharmacokinetic drawbacks evidenced by rapid systemic clearance, low oral bioavailability, and poor aqueous solubility requiring high doses for therapeutic action. Novel formulation strategies like solid dispersions, liposomal formulations, and PEGylated and hybrid nanoparticles enhance DSB's pharmacokinetic and pharmacodynamic profiles by enhancing drug solubility, stability, and controlled release. In addition, through these targeted drug-delivery systems based on ligand-functionalized nanoparticles and antibody–drug conjugates-the tumor-targeted DSB is allowed selective accumulation at the tumor site, causing fewer off-target effects and lessening systemic toxicity while maximizing effectiveness. These approaches are geared toward utilizing nanotechnology to improve intracellular drug uptake and extend the circulation time to optimize antitumor efficacy. Overall, those advances in drug delivery systems could greatly boost the therapeutic efficacy of DSB by providing better bioavailability, controlled release, and targeted distribution. Such advances would increase treatment success in CML and Ph + ALL and expand DSB's potential clinical applications toward other malignancies. Research concerning the delivery of DSB with nanocarriers and ligand-mediated targeting strategies should bear further fruits to augment DSB therapy in oncology. Graphical Abstract

Correction: Electrosprayed Janus Particles for Combined Photo-Chemotherapy - Brenda Sanchez-Vazquez; Adérito J. R. Amaral; Deng-Guang Yu; George Pasparakis; Gareth R. Williams (AAPS PharmSciTech, 2025)

Leveraging Nanoscience and Strategic Delivery for the Expedition of Osteoporosis - Pramoda G; Rahul K. Verma; Rahul Shukla (AAPS PharmSciTech, 2025)

AG86 Peptide-modified Reactive Oxygen Species-responsive Polymer Nanovesicles for Transdermal Delivery of Hydrophilic Ergothioneine to Basal Keratinocytes - Junlong Chen; Yiqing Long; Xiaozeliang Zhou; Zongning Yin (AAPS PharmSciTech, 2025)

Oleogel-mediated Topical Administration of Roflumilast and Paclitaxel as a Synergistic Strategy to Combat Imiquimod-induced Psoriasis - Wenxiu Pan; Yunyi Shi; Fei Sun; Meijuan Zou; Hongyu Piao (AAPS PharmSciTech, 2025)

Design, Development, and Characterization of High Drug-Loaded Drug-Drug-Polymer Ternary Amorphous Solid Dispersions - Sagar Kumar Paul; Dunesh Kumari; Joel Destino; Harsh Chauhan (AAPS PharmSciTech, 2025)

Development and Characterization of Chitosan Nanoparticles Containing Quercetin-β-Cyclodextrin Inclusion Complex for Improved Solubility, Brain Targeting, and Neuroprotective Potential Against Epilepsy - Priyabrata Pradhan; Vineet Kumar Rai; Jitu Halder; Durgamadhab Kar; Shakti Ketan Prusty; Saroj Kumar Rout; Salim Manoharadas; Subramanian Palanisamy; Priyanka Dash; Chandan Das; Biswakanth Kar; Goutam Ghosh; et al. (AAPS PharmSciTech, 2025)

Ethyl-Cellulose Nanosponges for Topical Delivery of Simvastatin with Preferential Skin Retention for Wound Healing in a Full-Thickness Wound Rat Model - Samar Aboelazayem; Maha Nasra; Heba Ebada; Ossama Abdallah (AAPS PharmSciTech, 2025)
Novel topical nanosponges were implemented to improve the skin availability of simvastatin (SV) for treating full-thickness wounds while controlling the scarring process. SV exhibits great potential in treating various skin diseases owing to its antibacterial, antioxidant, anti-inflammatory, and immunomodulatory properties. However, its poor oral bioavailability and systemic side effects have hindered its clinical application in dermatology. For the first time, nanosponges were utilized to target injured skin, creating an SV reservoir within the wound bed to enhance therapeutic efficacy while minimizing adverse effects. Herein, SV-loaded ethyl-cellulose nanosponges (SV-NS) were prepared using the emulsion solvent evaporation technique, optimizing organic solvents, SV concentration, and stabilizer concentration. The selected SV-NS (20 mg SV) exhibited nanoporous particles (786.2 ± 50 nm), a specific surface area of 10.3 m 2 /g, and a total pore volume of 0.016 cm 3 /g, offering sustained release and enhanced skin retention capacity. In vivo studies on full-thickness rat wounds confirmed that topical SV-NS (5 mg SV, applied every 5 days) significantly accelerated wound closure ( P P Graphical Abstract

Enhancing Intracellular Uptake of Ivermectin through Liposomal Encapsulation - Meryem Kocas; Fumiyoshi Yamashita; Tansel Comoglu; Qiyue Zhang (AAPS PharmSciTech, 2025)
Ivermectin (IVM), an antiparasitic drug approved by the Food and Drug Administration (FDA), is widely used to treat several neglected tropical diseases, including onchocerciasis, helminthiases, and scabies. Additionally, IVM has shown potential as a potent inhibitor of certain RNA viruses, such as SARS-CoV-2. However, IVM is highly hydrophobic, essentially insoluble in water, which limits its bioavailability and therapeutic effectiveness. The use of liposomes as drug carriers offers several advantages, including enhanced solubility for lipophilic drugs, passive targeting of immune system cells, sustained release, and improved tissue penetration. To address the limitations of IVM, including its poor solubility and bioavailability, liposomal formulations were developed using a combination of soyphosphatidylcholine (SPC), dioleylphosphatidylcholine (DOPC), cholesterol (Ch), and diethylphosphate (DCP) in two distinct molar ratios (1.85:1:0.15 and 7:2:1) via the ethanol injection method. The physicochemical properties of the placebo and IVM-loaded liposomes were extensively characterized in our earlier study, including the particle size, polydispersity index, and zeta potential. The present work adds a deeper level of investigation into how to effect cellular uptake and cytotoxicity in vitro of both free IVM and IVM-loaded liposomes in Vero E6 cells. The half-maximal cytotoxic concentrations (CC 50 ) for free IVM and IVM-loaded liposomes were 10 μM and > 110 μM, respectively and the cellular uptake of IVM-loaded liposomes ranged from 13 to 60%, whereas free IVM showed a significantly lower uptake of only 2%. These results demonstrate that liposomal encapsulation effectively enhances IVM’s cellular uptake while reducing its cytotoxicity, thus offering a promising strategy for improving the effectiveness of IVM. Graphical Abstract

Application of a Two-Phase Experiment Design and Optimization Method to Formulate Ciprofloxacin-Loaded Bovine Serum Albumin Nanoparticles with High-Entrapment Efficiency for Targeting Urinary Tract Infections - Sofía V. Sánchez; Erlen Cruz Jorge; Nicolás Navarro M.; María José González; Ricardo Vásquez; Felipe Del Canto; Paola Scavone; Eva C. Arrúa; Javier O. Morales (AAPS PharmSciTech, 2025)

Predicting and Confirming Bioequivalence of Alpelisib Oral Granules and Tablets for Patients With PIK3CA-Related Disorders - Elise Burmeister Getz; Séverine Niglis; Athanasia Papadimitriou; Marina Statelova; Xiaojun Ren; Keroles Nakhla; Sherif Sharaby; Muzammil Tariq; Luca Garbuio; Sumerah Bakhsh (AAPS PharmSciTech, 2025)
Alpelisib, an oral α-specific phosphoinositide 3-kinase ( PI3K ) inhibitor, has been shown to be safe and effective for some patients with gain-of-function mutation in the PIK3CA oncogene. Alpelisib has received US FDA accelerated approval as Vijoice® film-coated tablets to treat severe PIK3CA -Related Overgrowth Spectrum (PROS). PROS typically displays clinical manifestations in the first year of patient life. Therefore, oral granules were developed as an age-appropriate pediatric dosage form. Bioequivalence between alpelisib granules and tablet and the effect of food on granules pharmacokinetics were assessed in a single-center, randomized, three-treatment, six-sequence, three-period, crossover study among 60 healthy adults. Participants were randomly assigned to receive a single 50-mg alpelisib dose as: (i) tablet following a meal, (ii) granules following a meal, and (iii) granules while fasting. Statistical analysis of non-compartmental pharmacokinetic parameters demonstrated bioequivalence between the 50-mg alpelisib granules and tablet forms when administered with food: estimated geometric mean ratios (90% confidence interval) for granules-versus-tablet area under the curve (AUC) from time zero to infinity (AUC inf ), to the last measurable concentration (AUC last ) and maximum observed concentration (C max ) were 0.984 (0.952, 1.02), 0.980 (0.946, 1.02), and 0.947 (0.891, 1.01), respectively. No clinically relevant food effect on 50-mg alpelisib granules pharmacokinetics was observed. These results were accurately predicted using physiologically based biopharmaceutical modeling. Alpelisib granules provide a bioequivalent alternative to tablets for patients prescribed a 50-mg dose and have difficulty swallowing tablets, an important consideration for convenience and compliance of this standard-of-care chronic therapy for patients with PROS. This study was registered in ClinicalTrials.gov on January 4, 2022 (NCT05195892). Graphical Abstract

Solubilising and Aerosolising Cannabidiol Using Methyl β-Cyclodextrin and Human Serum Albumin - Waiting Tai; Dipesh Khanal; Jonathon Carl Arnold; Hak-Kim Chan; Philip Chi Lip Kwok (AAPS PharmSciTech, 2025)
Pulmonary delivery can deliver cannabidiol (CBD) with high bioavailability and fast onset of action. One formulation obstacle is the low aqueous solubility of CBD, so solubilsers are necessary. This study aimed to develop inhalable CBD powders using excipients that help dissolving CBD. The solubilisation effects of human serum albumin (HSA), β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and methyl-β-cyclodextrin (mbCD) were investigated with phase solubility test. MbCD showed the highest CBD solubilisation ability at all tested concentrations, followed by HSA. Therefore, mbCD and HSA were co-spray freeze dried with CBD to obtain CBD + mbCD and CBD + HSA powders, respectively. Both powders were amorphous, had vs 53.5 ± 1.5%). The higher level of CBD solubility enhancement and better aerosol performance from mbCD indicated that it was an effective excipient to deliver CBD and potentially other cannabinoids in the future. Graphical Abstract

Functionalized Niosomes for Co-Delivery of Curcumin and Imatinib Mesylate to Treat Breast Cancer: In Vitro and In Vivo Investigations - Priyadarshi Aparajay; Harishkumar Madhyastha; Mohammad A. Altamimi; Abhimanyu Dev; Afzal Hussain; Shuvadip Bhowmik (AAPS PharmSciTech, 2025)

Thermo-Responsive Niosomal In Situ Gels for Topical Delivery of Prednisolone - Rania Hamed; Rafa Aburayya; Ahlam Zaid Alkilani; Alaa M. Hammad; Osama H. Abusara; Hadeel Abo-Zour (AAPS PharmSciTech, 2025)

Dual-Responsive Ion-Exchange Resin Encapsulated Atomoxetine Hydrochloride for Taste-Masking and Biphasic Release - Tao Xiao; Quanzhu Yang; Lusi Chen; Jiayu Xie; Huiying Zhong; Guoqing Zhang; Haibing He; Hongfei Liu (AAPS PharmSciTech, 2025)

Isotretinoin-Loaded Topical Lipid Liquid Crystal for the Treatment of Acne: In-Vitro and In-Vivo Evaluations - Armita Sedighidarijani; Shiva Golmohammadzadeh; Hossein Kamali; Bahman Khameneh; Elham Khodaverdi; Ali Nokhodchi (AAPS PharmSciTech, 2025)
Effective acne treatment is critical due to its profound impact on physical and psychological well-being. It was shown that severe systemic side effects, including teratogenicity, ovarian reserve reduction, depression, dry skin, hypertriglyceridemia, and intracranial hypertension limited oral isotretinoin usage. Therefore, this study addresses these challenges by developing isotretinoin-loaded lipid liquid crystal (LLC-IT) nanoparticles for topical application, aiming to enhance localized delivery while minimizing systemic exposure. LLC-IT nanoparticles were prepared using a top-down method and evaluated for their physicochemical properties, photostability, cytotoxicity, antimicrobial activity, in-vitro drug release, and in-vivo therapeutic efficacy. A testosterone-induced acne mouse model was used to compare LLC-IT treatment with untreated and commercial isotretinoin gel-treated groups. LLC-IT nanoparticles exhibited a uniform particle size (69.57 ± 0.51 nm), low polydispersity index (0.264 ± 0.01), and stable zeta potential (- 19.3 ± 0.2 mV). High encapsulation efficiency (95% ± 3) and effective loading capacity (1.15% ± 0.13) were achieved. Drug release was diffusion-controlled with minimal UV-induced degradation. Stability assessments over 12 months confirmed consistent properties across varying storage temperatures. LLC-IT displayed significant antibacterial activity and reduced skin irritation in Draize tests compared to commercial gels. In-vivo , LLC-IT reduced inflammation significantly more than untreated or commercial gel-treated groups, indicating enhanced therapeutic efficacy of LLC-IT formulation. The isotretinoin-loaded lipid liquid crystal formulation shows superior stability and efficacy with reduced side effects compared to conventional treatments, offering a more effective and patient-friendly solution, as well as a promising alternative for industrial production in acne management. Graphical Abstract

Carboplatin Co-loaded 5-Fluorouracil Nanoparticles Conjugated with Trastuzumab for Targeted Therapy in HER2+ Heterogeneity Breast Cancer - Akshay Kumar Lunawat; Debanjan Mukherjee; Riya Shivgotra; Sarjana Raikwar; Ankit Awasthi; Amrinder Singh; Shamsher Singh; Shivani Chandel; Subheet Kumar Jain; Shubham Thakur (AAPS PharmSciTech, 2025)

Integration of Synchronizing In Silico, In Vitro, and In Vivo Strategies for the Development of Antipsoriatic Apremilast-loaded Nanostructured Lipid Carrier Embedded in Hydrogel - Nikita Patel; Aneri Desai; Bhavin Vyas; Pranav Shah; Mangrulkar Shubhada; Umekar Milind; Kamla Pathak; Mahavir Bhupal Chougule (AAPS PharmSciTech, 2025)

Collagenase-functionalized Liposomes Based on Enhancing Penetration into the Extracellular Matrix Augment Therapeutic Effect on Idiopathic Pulmonary Fibrosis - Xiaoqing Liu; Xiaoling Dong; Zhen Peng; Cuihong Wang; Jianwei Wan; Min Chen; Chunli Zheng (AAPS PharmSciTech, 2025)

Sericin from Bombyx Mori as a By-product for DLP 3D Printing in Pharmaceutical and Biomedical Applications - Éverton da Silva Santos; Denise Tiemi Uchida; Marcos Luciano Bruschi (AAPS PharmSciTech, 2025)

Formononetin-Loaded PLGA Large Porous Microparticles via Intratracheal Instillation for Bleomycin-Induced Pulmonary Fibrosis Treatment - Hongting Liu; Yao Sun; Shihao Cai; Conglu Zhao; Xiang xu; Aiguo Xu; Honggang Zhou; Cheng Yang; Xiaoting Gu; Xiaoyu Ai (AAPS PharmSciTech, 2025)

Cyclosporine a Eluting Nano Drug Reservoir Film for the Management of Dry Eye Disease - Pinal Chaudhari; Vivek M. Ghate; Madhavan Nampoothiri; Shaila A. Lewis (AAPS PharmSciTech, 2025)
Cyclosporine A (CsA) is widely used to treat dry eye disease (DED), and ocular morbidity is on the rise and is a growing concern globally. However, several drug and formulation challenges, such as poor drug solubility, short pre-corneal residence time, and poor patient compliance, have limited the ocular bioavailability of CsA to in vitro drug release, ex vivo corneal permeation, and in vivo precorneal retention. Preclinical efficacy studies were performed to assess the efficacy of CsA-complex-loaded nano-reservoirs in an experimental dry-eye mouse model. Physicochemical characterization confirmed the formation of a stable complex and the improved solubility of CsA. In vitro release and ex vivo permeation studies indicated a controlled drug release and improved permeation, respectively. Furthermore, tear volume measurement and corneal damage assessment using slit-lamp imaging suggested decreased dry eye symptoms, significantly increasing tear volume in the drug-loaded nano-reservoir-treated group. Moreover, histopathological studies corroborated the tear volume and slit-lamp imaging results, with reduced inflammation and neovascularization. The poorly water-soluble drug with cyclodextrin complex incorporated nanoreservoir films presents a potential alternative for managing various ocular diseases. Graphical Abstract

Proposals for Global Harmonization of Regulations for Testing of Spacers and Valved Holding Chambers for Pressurized Metered Dose Inhalers - Jolyon P. Mitchell (AAPS PharmSciTech, 2025)

Formulation Strategy of BCS-II Drugs by Coupling Mechanistic In-Vitro and Nonclinical In-Vivo Data with PBPK: Fundamentals of Absorption-Dissolution to Parameterization of Modelling and Simulation - Shriya V A; Usha Y. Nayak; Muddukrishna Badamane Sathyanarayana; Bhim Bahadur Chaudhari; Krishnamurthy Bhat (AAPS PharmSciTech, 2025)
BCS class II candidates pose challenges in drug development due to their low solubility and permeability. Researchers have explored various techniques; co-amorphous and solid dispersion are major approaches to enhance in-vitro drug solubility and dissolution. However, in-vivo oral bioavailability remains challenging. Physiologically based pharmacokinetic (PBPK) modeling with a detailed understanding of drug absorption, distribution, metabolism, and excretion (ADME) using a mechanistic approach is emerging. This review summarizes the fundamentals of the PBPK, dissolution—absorption models, parameterization of oral absorption for BCS class II drugs, and provides information about newly emerging artificial intelligence/machine learning (AI/ML) linked PBPK approaches with their advantages, disadvantages, challenges and areas of further exploration. Additionally, the fully integrated workflow for formulation design for investigational new drugs (INDs) and virtual bioequivalence for generic molecules falling under BCS-II are discussed. Graphical Abstract

The Amorphous State of the Antiepileptic Clobazam: Preparation and Characterization - Marina M. Marcos Valdez; Julio Sanchez; María E. Bertotto; Octavio E. Fandiño; Fernando P. Cometto; Norma R. Sperandeo (AAPS PharmSciTech, 2025)

RETRACTED ARTICLE: Nasal In-Situ Gels of Brij®-Enriched Novasomes as Optimistic Nanovesicular Carriers for Enhancing Anti-Depressant Action of Agomelatine - Tarek M. Ibrahim; Ayman M. Fathi; Nourhan A. Abdulla (AAPS PharmSciTech, 2025)