Evaluation of in vitro Skin Permeation of Clascoterone From Clascoterone Topical Cream, 1% (w/w) - Yang Yang; Jiang Wang; Apipa Wanasathop; Mengmeng Niu; Priyanka Ghosh; Ahmed Zidan; Jianghong Gu; Robert Hunt; Patrick Faustino; Muhammad Ashraf; Xiaoming Xu (AAPS PharmSciTech, 2024)

Strategy to Improve the Oral Pharmacokinetics of Cyclin-Dependent Kinase 4/6 Inhibitors: Enhancing Permeability and CYP450 Inhibition by a Natural Bioenhancer - Prajakta Harish Patil; Mrunal Pradeep Desai; Rajat Radhakrishna Rao; Srinivas Mutalik; Jagadish Puralae Channabasavaiah (AAPS PharmSciTech, 2024)
Palbociclib and ribociclib an orally bioavailable, potent cyclin-dependent kinase 4/6 inhibitors, with low oral bioavailability due to substrate specificity towards CYP3A and P-glycoprotein. Thus, current research aims to examine the effect of a bioenhancer (naringin), on oral pharmacokinetics of palbociclib and ribociclib. Naringin’s affinity for CYP3A4 and P-glycoprotein was studied using molecular docking; its impact on palbociclib/ribociclib CYP3A metabolism and P-glycoprotein-mediated efflux was examined using in vitro preclinical models; and its oral pharmacokinetics in rats were assessed following oral administration of palbociclib/ribociclib in presence of naringin (50 and 100 mg/kg). Naringin binds optimally to both proteins with the highest net binding energy of − 1477.23 and − 1607.47 kcal/mol, respectively. The microsomal intrinsic clearance of palbociclib and ribociclib was noticeably reduced by naringin (5–100 µM), by 3.0 and 2.46-folds, respectively. Similarly, naringin had considerable impact on the intestinal transport and efflux of both drugs. The pre-treatment with 100 mg/kg naringin increased significantly ( p Graphical Abstract

Effects and Action Mode of Oleic Acid and Azone on Release and Penetration Process of Levothyroxine Sodium Patches - Xing Li; Kaili Liang; Yingying Dong; Shen Li; Zhengnan Gao; Qing Wang (AAPS PharmSciTech, 2024)

Synthesis of Quarternized Chitosans and Their Potential Applications in the Solubility Enhancement of Indomethacin by Solid Dispersion - Sasikarn Sripetthong; Sirinporn Nalinbenjapun; Abdul Basit; Chitchamai Ovatlarnporn (AAPS PharmSciTech, 2024)

Quality by Design in Pulmonary Drug Delivery: A Review on Dry Powder Inhaler Development, Nanotherapy Approaches, and Regulatory Considerations - Ashish Dilip Sutar; Rahul Kumar Verma; Rahul Shukla (AAPS PharmSciTech, 2024)

Bioadhesive Polymeric Films Containing Rhamnolipids, An Innovative Antimicrobial Topical Formulation - Jéssica B. Carra; Kamila B. B. Wessel; Giovana N. Pereira; Mariana C. Oliveira; Pietra M. T. Pattini; Bianca L. Masquetti; Ismael R. Amador; Marcos L. Bruschi; Rúbia Casagrande; Sandra R. Georgetti; Waldiceu A. Verri; Gerson Nakazato; et al. (AAPS PharmSciTech, 2024)

Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile - Mohini Mishra; Rinki Verma; Aditya Sharma; Krishan Kumar; Ruchi Chawla (AAPS PharmSciTech, 2024)

An Advanced Twin-Screw Granulation Technology: The use of Non-Volatile Solvents with High Solubilizing Capacity - Siva Satyanarayana Kolipaka; Laura Andrade Junqueira; Steven Ross; Vivek Garg; Md Sadeque Hossein Mithu; Saumil Bhatt; Dennis Douroumis (AAPS PharmSciTech, 2024)
Purpose Twin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders. Methods Herein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat ® 603, Affinisol™, and AQOAT ® ). Results The physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity. Conclusions Overall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings. Graphical Abstract

Development and In vivo Evaluation of Atomoxetine Hydrochloride ODMTs in a Nicotine-induced Attention Deficit Hyperactivity Disorder (ADHD) Model in Rats - Özbeyen Atalay; Emine Dilek Ozyilmaz; Deniz Önal; Bilge Pehli̇vanoğlu; Tansel Çomoğlu (AAPS PharmSciTech, 2024)
The current study aimed to evaluate the efficacy of orally administered rapid mini-tablets containing atomoxetine hydrochloride (ODMT) relative to the conventional capsule formulation of atomoxetine hydrochloride (ATO). To mask the bitter taste of ATO and render it more palatable for pediatric administration in individuals with Attention Deficit Hyperactivity Disorder (ADHD), an inclusion complex of ATO with β-cyclodextrin (β-CD) was synthesized. The ODMT and conventional capsule ATO formulations were administered orally to a cohort of ADHD rat pups born to nicotine-exposed dams, facilitating an in vivo efficacy assessment. Behavioral assays, including the open field test, novel object recognition test, and Barnes maze test, were conducted pre- and post-administration of the therapeutics. The outcomes suggested that the ODMT formulation, incorporating ATO-β-CD inclusion complexes, shows promise as a viable alternative to the capsule form of ATO. Conclusively, the preparation of the ATO-β-CD complexes and ODMTs leveraged a factorial experimental design, with the animal model being subjected to nicotine-induced hyperactivity to provide a unique evaluative framework for the ODMT formulation under development. Graphical Abstract

Retraction Note: EGFR Targeted Paclitaxel and Piperine Co-loaded Liposomes for the Treatment of Triple Negative Breast Cancer - Ankita Sanjay Burande; Matte Kasi Viswanadh; Abhishek Jha; Abhishesh Kumar Mehata; Azad Shaik; Nishi Agrawal; Suruchi Poddar; Sanjeev Kumar Mahto; Madaswamy S. Muthu (AAPS PharmSciTech, 2024)

Unleashing the Potential of β –cyclodextrin Inclusion Complexes in Bitter Taste Abatement: Development, Optimization and Evaluation of Taste Masked Anti-emetic Chewing Gum of Promethazine Hydrochloride - Prerna Kaushik; Vineet Mittal; Deepak Kaushik (AAPS PharmSciTech, 2024)

Current Trends and Innovative Approaches in Cancer Immunotherapy - Jaechang Kim; Ruby Maharjan; Jonghyuck Park (AAPS PharmSciTech, 2024)

Formulation and Evaluation of Meloxicam Hybrid nano Particles - Mohammed Asif; Kaneez Fatima; Syed Sarim Imam; Sultan Alshehri; Wael A. Mahdi (AAPS PharmSciTech, 2024)

Intestinal Absorption Site-Guided Development and Evaluation of Oral Disintegrating Controlled Release Tablets of Mirabegron - Mohammed I. Ghanem; Shimaa M. Ashmawy; Gamal M. El Maghraby (AAPS PharmSciTech, 2024)
The aim was to employ site-dependent absorption of mirabegron ( MB ) as a guide for fabrication of oral disintegrating controlled release tablet (ODCRT) which undergoes instantaneous release of loading fraction followed by delayed release of the rest of MB. The goal was to release MB in a manner consistent with the chronobiology of overactive bladder (OAB) syndrome. In situ rabbit intestinal permeability of MB was adopted to assess absorption sites. MB was subjected to dry co-grinding with citric acid to develop the fast-dissolving fraction in the mouth. Delayed release fraction was formulated by ethanol-assisted co-processing with increasing proportions of Eudragit polymer (S100) as pH responsive polymer. The developed dry mixtures underwent thermal (DSC) and physical (X-ray diffraction) characterization, in addition to in vitro release behavior. Optimized fast dissolving and delayed release formulations were mixed with tablet excipient before compression in ODCRT which was assessed for release profile using continuous pH variation. MB underwent preferential permeation through ileum and colon. Co-grinding with citric acid provided co-amorphous powder with fast dissolution. Co-amorphization of MB with Eudragit S100 (1:5) showed pH-dependent release to release most of the dose at pH 7.4. The developed ODCRT released 43.5% of MB in the buccal environment and retained MB at acidic pH to start release at pH 7.4. The study successfully fabricated ODCRT guided by site-dependent absorption. The ODCRT instantaneously released loading fraction to support the patient after administration with delayed fraction to sustain the effect. Graphical Abstract

Correction: Formulation and Antimycotic Evaluation of Colloidal Itraconazole-Loaded Metered Dose Sprays for Treating Superficial Mycoses - Emmanuel Uronnachi; Titpawan Nakpheng; Thaddeus Gugu; Teerapol Srichana (AAPS PharmSciTech, 2024)

Enhanced Skin Penetration and Efficacy: First and Second Generation Lipoidal Nanocarriers in Skin Cancer Therapy - Palak Sharma; Shreya Kaul; Neha Jain; Manisha Pandey; Upendra Nagaich (AAPS PharmSciTech, 2024)

Ultrasonic Preparation of Nano-CaCO3 Templates and Hollow Mesoporous SiO2 Nanoparticles for Voriconazole Loading - Xiaolin Liu; Zhilin Wu; Roberta Cavalli; Maela Manzoli; Giancarlo Cravotto (AAPS PharmSciTech, 2024)
CaCO 3 nanoparticles (nano-CaCO 3 ) as nano-templates were prepared using CaCl 2 and Na 2 CO 3 solutions under controlled sonication (19.5 kHz). Using the same ultrasonic device, subsequently, hollow mesoporous silica nanoparticles (HMSNs) were obtained by the hard template of nano-CaCO 3 . HMSNs were selected as carriers for the antifungal drug voriconazole (VOR) loading to overcome poor water solubility. Three-dimensional CaCO 3 nanosheets HMSNs were obtained under gentle sonication. Three-dimensional CaCO 3 nanosheets of 24.5 nm (hydrodynamic diameter) were obtained under 17.6 W for 3 min. HMSNs were synthesized by double-template method with nano-CaCO 3 as the hard template. Transmission electron microscopy measurements showed that the prepared HMSNs possess hollow structures with particle size between 110 and 120 nm. Nitrogen physisorption at -196 °C revealed that the HMSNs had high surface area (401.57 m 2 /g), high pore volume (0.11 cm 3 /g), and uniform pore size (2.22 nm) that facilitated the effective encapsulation of VOR in the HMSNs. The loading capacity of VOR (wt%) on the HMSNs was 7.96%, and the total VOR release amount of VOR-HMSNs material was 71.40% at 480 min. The kinetic model confirmed that the release mechanism of HMSNs nanoparticles followed Fickian diffusion at pH = 7.4 and 37 °C. Moreover, the cumulative VOR release at 42 °C (86.05%) was higher than that at 37 °C (71.40%). The cumulative release amount of VOR from the VOR-HMSNs material was 92.37% at pH = 5.8 at the same temperature. Both nano-CaCO 3 templates and HMSNs were prepared by sonication at 19.5 kHz. The as-prepared HMSNs can effectively encapsulate VOR and released drug by Fickian diffusion. Graphical Abstract

An Insight Into Risk Assessment and Reformulation of Drug Products Manufactured Using Benzene Grade Carbomer: A Regulatory Perspective - Kailash Bansal; Anil B. Jindal (AAPS PharmSciTech, 2024)

Effects of Commonly used Surfactants, Poloxamer 188 and Tween 80, on the Drug Transport Capacity of Intestinal Glucose Transporters - Jiasheng Chen; Zhenzhen Chen; Wentao Wang; Liyang Wang; Jiaqi Zheng; Shiqiong Wu; Yuru Pan; Sai Li; Jie Zhao; Zheng Cai (AAPS PharmSciTech, 2024)

Design of Experiments-Driven Optimization of Spray Drying for Amorphous Clotrimazole Nanosuspension - Bhavin Gajera; Harsh Shah; Bhavin Parekh; Vishal Rathod; Mitul Tilala; Rutesh H. Dave (AAPS PharmSciTech, 2024)

Preparation of Microsponge Drug Delivery System (MSDDS) Followed by a Scale-Up Approach - S. Halder; U. S. Behera; S. Poddar; J. Khanam; S. Karmakar (AAPS PharmSciTech, 2024)

Nanosuspension-Based Repaglinide Fast-Dissolving Buccal Film for Dissolution Enhancement - Hamsa Yaseen Ghadhban; Kawther Khalid Ahmed (AAPS PharmSciTech, 2024)

HSPiP, Computational, and Thermodynamic Model–Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus‑Based In Vivo Prediction in Humans: Part II - Tasneem Khan; Afzal Hussain; Mohd Usman Mohd Siddique; Mohammad A. Altamimi; Abdul Malik; Zahid Rafiq Bhat (AAPS PharmSciTech, 2024)

Understand the Stabilization Engineering of Ascorbic Acid, Mapping the Scheme for Stabilization, and Advancement. - Om Shelke; Krishna Phani Chandra Susarla; Manish Bankar (AAPS PharmSciTech, 2024)

Correction: Development of 3D DLP Printed Sustained Release Ibuprofen Tablets and Their Pharmacokinetic Evaluation in Rats - Keb Mosley-Kellum; Arvind Bagde; Shawn Spencer; Satyanarayan Dev; Mandip Singh (AAPS PharmSciTech, 2024)

Formulation and Antimycotic Evaluation of Colloidal Itraconazole-Loaded Metered Dose Sprays for Treating Superficial Mycoses - Emmanuel Uronnachi; Titpawan Nakpheng; Thaddeus Gugu; Teerapol Srichana (AAPS PharmSciTech, 2024)

Pharmacokinetics and Histotoxic Profile of a Novel Azithromycin-Loaded Lipid-Based Nanoformulation - Aziz Ur Rahman; Munasib Khan; Mir Azam Khan; Maqsood Ur Rehman; Abdullah; Saeed Ahmed (AAPS PharmSciTech, 2024)

Characterization of Prototype Gummy Formulations Provides Insight into Setting Quality Standards - Oluwatoyin A. Adeleke; Saba Abedin (AAPS PharmSciTech, 2024)

Recent Update on Nanocarrier(s) as the Targeted Therapy for Breast Cancer - Debanjan Mukherjee; Sarjana Raikwar (AAPS PharmSciTech, 2024)

Preparation and Evaluation of Berberine-Excipient Complexes in Enhancing the Dissolution Rate of Berberine Incorporated into Pellet Formulations - Mohammadreza Abbaspour; Faezeh Faeznia; Parisa Zanjanian; Milad Ruzbehi; Kamran Shourgashti; Amirhosseinn Ziaee; Hossein Shahdadi Sardou; Ali Nokhodchi (AAPS PharmSciTech, 2024)
Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation. Graphical Abstract

A Quality by Design Approach for Optimizing Solid Lipid Nanoparticles of Bedaquiline for Improved Product Performance - Mercy A. Okezue; Chidi Uche; Adekoya Adebola; Stephen R. Byrn (AAPS PharmSciTech, 2024)

Formulation, Optimization and In-Vivo Characterization of Thermosensitive In-Situ Nasal Gel Loaded with Bacoside a for Treatment of Epilepsy - Someshwar Dattatray Mankar; Shraddha Ranjan Parjane; Suhas Shivaji Siddheshwar; Santosh Bhausaheb Dighe (AAPS PharmSciTech, 2024)

Advanced Delivery Strategies of Nintedanib for Lung Disorders and Beyond: A Comprehensive Review - Dhruti Thakkar; Sanskriti Singh; Sarika Wairkar (AAPS PharmSciTech, 2024)

Formulation and Characterization of Silibinin Entrapped Nano-Liquid Crystals for Activity against Aβ1-42 Neurotoxicity in In-Vivo Model - Ajit Singh; Debarati Rakshit; Ankit Kumar; Awanish Mishra; Rahul Shukla (AAPS PharmSciTech, 2024)

Croscarmellose Sodium as Pelletization Aid in Extrusion-Spheronization - Finn Siebel; Peter Kleinebudde (AAPS PharmSciTech, 2024)
Only few excipients are known to be suitable as pelletization aids. In this study, the potential use of croscarmellose sodium (CCS) as pelletization aid was investigated. Furthermore, the impact of cations on extrusion-spheronization (ES) of CCS was studied and different grades of CCS were tested. The influence of different cations on the swelling of CCS was investigated by laser diffraction. Mixtures of CCS with lactose monohydrate as filler with or without the inclusion of different cations were produced. The mixtures were investigated by mixer torque rheometry and consequently extruded and spheronized. Resulting pellets were analyzed by dynamic image analysis. In addition, mixtures of different CCS grades with dibasic calcium phosphate anhydrous (DP) and a mixture with praziquantel (PZQ) as filler were investigated. Calcium and magnesium cations caused a decrease of the swelling of CCS and influenced the use of CCS as pelletization aid since they needed to be included for successful ES. Aluminum, however, led to an aggregation of the CCS particles and to failure of extrusion. The inclusion of cations decreased the uptake of water by the mixtures which also reduced the liquid-to-solid-ratio (L/S) for successful ES. This was shown to be dependent on the amount of divalent cations in the mixture. With DP or PZQ as filler, no addition of cations was necessary for a successful production of pellets, however the optimal L/S for ES was dependent on the CCS grade used. In conclusion, CCS can be used as a pelletization aid. Graphical Abstract

Oleogels: Versatile Novel Semi-Solid System for Pharmaceuticals - Vaishnavi U. Pawar; Akanksha D. Dessai; Usha Y. Nayak (AAPS PharmSciTech, 2024)
Oleogels is a novel semi-solid system, focusing on its composition, formulation, characterization, and diverse pharmaceutical applications. Due to their stability, smoothness, and controlled release qualities, oleogels are frequently utilized in food, cosmetics, and medicinal products. Oleogels are meticulously formulated by combining oleogelators like waxes, fatty acids, ethyl cellulose, and phytosterols with edible oils, leading to a nuanced understanding of their impact on rheological characteristics. They can be characterized by methods like visual inspection, texture analysis, rheological measurements, gelation tests, and microscopy. The applications of oleogels are explored in diverse fields such as nutraceuticals, cosmetics, food, lubricants, and pharmaceutics. Oleogels have applications in topical, transdermal, and ocular drug delivery, showcasing their potential for revolutionizing drug administration. This review aims to enhance the understanding of oleogels, contributing to the evolving landscape of pharmaceutical formulations. Oleogels emerge as a versatile and promising solution, offering substantial potential for innovation in drug delivery and formulation practices. Graphical Abstract

Mucoadhesive Chitosan Composite Sponge as a Carrier for β-Sitosterol Cubosomes for Thermal Burn Treatment - Abeer Khattab; Soha Ismail; Areeg M. Abd-Elrazek (AAPS PharmSciTech, 2024)
Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the β-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the β-sitosterol product (Mebo)®. Graphical Abstract

Development of Lipid Polymer Hybrid Nanoparticles of Abietic Acid: Optimization, In-Vitro and Preclinical Evaluation - Ameeduzzafar Zafar; Mohd Yasir; Dibya Sundar Panda; Mohammad Khalid; Lubhan Singh; Anwarulabedin Mohsin Quazi (AAPS PharmSciTech, 2024)

Mixed-Micelle in Situ Gel as a Candidate for Oral Inflammatory Ulcerative Diseases - Niloofar Haghighatseir; Negin Mozafari; Elnaz Shadvand; Hajar Ashrafi; Saeid Daneshamouz; Amir Azadi (AAPS PharmSciTech, 2024)

Automated Tomographic Assessment of Structural Defects of Freeze-Dried Pharmaceuticals - Patric Müller; Achim Sack; Jens Dümler; Michael Heckel; Tim Wenzel; Teresa Siegert; Sonja Schuldt-Lieb; Henning Gieseler; Thorsten Pöschel (AAPS PharmSciTech, 2024)
The topology and surface characteristics of lyophilisates significantly impact the stability and reconstitutability of freeze-dried pharmaceuticals. Consequently, visual quality control of the product is imperative. However, this procedure is not only time-consuming and labor-intensive but also expensive and prone to errors. In this paper, we present an approach for fully automated, non-destructive inspection of freeze-dried pharmaceuticals, leveraging robotics, computed tomography, and machine learning.

Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells - Seyyed Mobin Rahimnia; Majid Saeedi; Jafar Akbari; Katayoun Morteza-Semnani; Akbar Hedayatizadeh-Omran; Rezvan Yazdian-Robati (AAPS PharmSciTech, 2024)

Laser-mediated Solutions: Breaking Barriers in Transdermal Drug Delivery - Ehsan Haghsay Khashechi; Abolfazl Afaghmehr; Niloofar Heidarizade; Ashkan Barfar; Javad Shokri (AAPS PharmSciTech, 2024)

Stealth Nanocarriers in Cancer Therapy: a Comprehensive Review of Design, Functionality, and Clinical Applications - Mohamed J. Saadh; Mohammed Ahmed Mustafa; Ashwani Kumar; Hassan Thoulfikar A. Alamir; Abhishek Kumar; Shaymaa Abdulhameed Khudair; Ahmed Faisal; Mahmood Hasen Shuhata Alubiady; Sarah Salah Jalal; Shafik Shaker Shafik; Irfan Ahmad; Faeza A. F. Khry; et al. (AAPS PharmSciTech, 2024)

Potential of Powder Rheology for Detecting Unforeseen Cross-Contamination of Foreign Active Pharmaceutical Ingredients - Shuichi Setoguchi; Shotaro Goto; Kazuhisa Matsunaga (AAPS PharmSciTech, 2024)

Proteomic Characterization of Human Placenta: Insights into Potential Therapeutic Applications for Osteoarthritis - Jithu Jerin James; K. V. Sandhya; K. N. Sridhar; S. Sudarson; B. V. Basavaraj; S. Bharath (AAPS PharmSciTech, 2024)

Scaffold-Mediated Drug Delivery for Enhanced Wound Healing: A Review - Mohd Sufiyan; Poonam Kushwaha; Mohammad Ahmad; Purba Mandal; Km Khushbo Vishwakarma (AAPS PharmSciTech, 2024)

Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications - Kavish Sanil; Ahmed Almotairy; Prateek Uttreja; Eman A. Ashour (AAPS PharmSciTech, 2024)

Lutein Loaded in β-Cyclodextrin Metal-Organic Frameworks for Stability and Solubility Enhancements - Hui Zhang; Liyun Dong; Tao Guo; Guoqing Zhang; Xinyue Ye; Xiaojian He; Qingfang Gao; Mubarak G. Bello; Can Peng; Li Wu; Jiwen Zhang (AAPS PharmSciTech, 2024)

Cocrystal Prediction of Nifedipine Based on the Graph Neural Network and Molecular Electrostatic Potential Surface - Yuting Wang; Yanling Jiang; Yu Zhou; Huai He; Jincao Tang; Anqing Luo; Zeng Liu; Chi Ma; Qin Xiao; Tianbing Guan; Chuanyun Dai (AAPS PharmSciTech, 2024)

QbD Assisted Systematic Review for Optimizing the Selection of PVP as a Ternary Substance in Enhancing the Complexation Efficiency of Cyclodextrins: a Pilot Study - Glovanna Mulenga; Teejan Ameer Abed Alahmed; Farheen Sami; Shahnaz Majeed; Md Sajid Ali; Janice Lo Jia Le; Carol Lee Qhai Rhu; Rajesh Sreedharan Nair; Nadeem Hasan; Mohammed Tahir Ansari (AAPS PharmSciTech, 2024)

Lipoplexes’ Structure, Preparation, and Role in Managing Different Diseases - Sally A. El-Zahaby; Lovepreet Kaur; Ankur Sharma; Aprameya Ganesh Prasad; Atif Khurshid Wani; Rattandeep Singh; Mohamed Y. Zakaria (AAPS PharmSciTech, 2024)

Application of Quality by Design in the Development of Hydrogen Sulfide Donor Loaded Polymeric Microparticles - Anjali Rai; Susmit Mhatre; Cole Chandler; Catherine Opere; Somnath Singh (AAPS PharmSciTech, 2024)
Hydrogen sulfide (H 2 S) is a multifaceted gasotransmitter molecule which has potential applications in many pathological conditions including in lowering intraocular pressure and providing retinal neuroprotection. However, its unique physicochemical properties pose several challenges for developing its efficient and safe delivery method system. This study aims to overcome challenges related to H 2 S toxicity, gaseous nature, and narrow therapeutic concentrations range by developing polymeric microparticles to sustain the release of H 2 S for an extended period. Various formulation parameters and their interactions are quantitatively identified using Quality-by-Design (QbD) approach to optimize the microparticle-based H 2 S donor (HSD) delivery system. Microparticles were prepared using a solvent-evaporation coacervation process by using polycaprolactone (PCL), soy lecithin, dichloromethane, Na 2 S.9H 2 O, and silicone oil as polymer, surfactant, solvent, HSD, and dispersion medium, respectively. The microparticles were characterized for size, size distribution, entrapment efficiency, and H 2 S release profile. A Main Effects Screening (MES) and a Response Surface Design (RSD) model-based Box-Behnken Design (BBD) was developed to establish the relationship between critical process parameters (CPPs) and critical quality attributes (CQAs) qualitatively and quantitatively. The MES model identified polymer to drug ratio and dispersion medium quantity as significant CPPs among others, while the RSD model established their quantitative relationship. Finally, the target product performance was validated by comparing predicted and experimental outcomes. The QbD approach helped in achieving overall desired microparticle characteristics with fewer trials and provided a mathematical relationship between the CPPs and the CQAs useful for further manipulation and optimization of release profile up to at least 30 days. Graphical Abstract

Accelerated Predictive Stability Study of a Pediatric Drug Product for a Supplemental New Drug Application - Viktoria Rakers; Jin Wang; Dawen Kou (AAPS PharmSciTech, 2024)

Naringenin-Zinc Oxide Nanocomposites Amalgamated Polymeric Gel Augmented Drug Delivery and Attenuated Experimental Cutaneous Candidiasis in Balb/c Mice: In Vitro and In Vivo Studies - Chanti babu Katta; Deepankar Bahuguna; Harithasree Veerabomma; Spandana Gollapalli; Arbaz Sujat Shaikh; Nagesh A. Bhale; Amol G. Dikundwar; Venkat Rao Kaki; Pankaj Kumar Singh; Jitender Madan (AAPS PharmSciTech, 2024)

Multivariate Analysis of Solubility Parameters for Drug-Polymer Miscibility Assessment in Preparing Raloxifene Hydrochloride Amorphous Solid Dispersions - Guilherme G. Moreira; Stephânia F. Taveira; Felipe T. Martins; Karl G. Wagner; Ricardo N. Marreto (AAPS PharmSciTech, 2024)

RETRACTED ARTICLE: Revolutionizing Lung Cancer Treatment: Innovative CRISPR-Cas9 Delivery Strategies - Dilpreet Singh (AAPS PharmSciTech, 2024)

Phosphatidylserine and/or Sialic Acid Modified Liposomes Increase Uptake by Tumor-associated Macrophages and Enhance the Anti-tumor Effect - Zihan Xu; Jie Li; Na Yan; Xinrong Liu; Yihui Deng; Yanzhi Song (AAPS PharmSciTech, 2024)

Navigating Skin Delivery Horizon: An Innovative Approach in Pioneering Surface Modification of Ultradeformable Vesicles - Devika Nayak; Mahalaxmi Rathnanand; Vamshi Krishna Tippavajhala (AAPS PharmSciTech, 2024)
In the dynamic landscape of pharmaceutical advancements, the strategic application of active pharmaceutical ingredients to the skin through topical and transdermal routes has emerged as a compelling avenue for therapeutic interventions. This non-invasive approach has garnered considerable attention in recent decades, with numerous attempts yielding approaches and demonstrating substantial clinical potential. However, the formidable barrier function of the skin, mainly the confinement of drugs on the upper layers of the stratum corneum, poses a substantial hurdle, impeding successful drug delivery via this route. Ultradeformable vesicles/carriers (UDVs), positioned within the expansive realm of nanomedicine, have emerged as a promising tool for developing advanced dermal and transdermal therapies. The current review focuses on improving the passive dermal and transdermal targeting capacity by integrating functionalization groups by strategic surface modification of drug-loaded UDV nanocarriers. The present review discusses the details of case studies of different surface-modified UDVs with their bonding strategies and covers the recent patents and clinical trials. The design of surface modifications holds promise for overcoming existing challenges in drug delivery by marking a significant leap forward in the field of pharmaceutical sciences.

Evaluation of Emulgel and Nanostructured Lipid Carrier-Based Gel Formulations for Transdermal Administration of Ibuprofen: Characterization, Mechanical Properties, and Ex-Vivo Skin Permeation - Duygu Yılmaz Usta; Zeynep Safak Teksin; Fatmanur Tugcu-Demiroz (AAPS PharmSciTech, 2024)
In transdermal applications of nonsteroidal anti-inflammatory drugs, the rheological and mechanical properties of the dosage form affect the performance of the drug. The aim of this study to develop emulgel and nanostructured lipid carrier NLC-based gel formulations containing ibuprofen, evaluate their mechanical properties, bioadhesive value and ex-vivo rabbit skin permeability. All formulations showed non-Newtonian pseudoplastic behavior and their viscosity values are suitable for topical application. The particle size of the nanostructured lipid carrier system was found to be 468 ± 21 nm, and the encapsulation efficiency was 95.58 ± 0.41%. According to the index of viscosity, consistency, firmness, and cohesiveness values obtained as a result of the back extrusion study, E2 formulation was found to be more suitable for transdermal application. The firmness and work of shear values of the E2 formulation, which has the highest viscosity value, were also found to be the highest and it was chosen as the most suitable formulation in terms of the spreadability test. The work of bioadhesion values of NLC-based gel and IBU-loaded NLC-based gel were found as 0.226 ± 0.028 and 0.181 ± 0.006 mJ/cm2 respectively. The percentages of IBU that penetrated through rabbit skin from the Ibuactive-Cream and the E2 were 87.4 ± 2.11% and 93.4 ± 2.72% after 24 h, respectively. When the penetration of ibuprofen through the skin was evaluated, it was found that the E2 formulation increased penetration due to its lipid and nanoparticle structure. As a result of these findings, it can be said that the NLC-based gel formulation will increase the therapeutic efficacy and will be a good alternative transdermal formulation. Graphical Abstract

Prolonged Release Niosomes For Ocular Delivery of Loteprednol: Ocular Distribution Assessment on Dry Eye Disease Induced Rabbit Model - Samet Ozdemir; Burcu Uner (AAPS PharmSciTech, 2024)

Development, Characterization and In Vitro Gastrointestinal Release of PLGA Nanoparticles Loaded with Full-Spectrum Cannabis Extracts - Aitor Villate; Gastón Pablo Barreto; Markel San Nicolás; Oier Aizpurua-Olaizola; Maitane Olivares; Aresatz Usobiaga (AAPS PharmSciTech, 2024)
Cannabinoids, such as ∆ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective bioactive compounds that improve the quality of life of patients with certain chronic conditions. The copolymer poly(lactic-co-glycolic acid) (PLGA) has been used to encapsulate such compounds separately, providing pharmaceutical grade edible products with unique features. In this work, a variety of PLGA based nanoformulations that maintain the natural cannabinoid profile found in the plant (known as full-spectrum) are proposed and evaluated. Three different cannabis sources were used, representing the three most relevant cannabis chemotypes. PLGA nanocapsules loaded with different amounts of cannabinoids were prepared by nanoemulsion, and were then functionalized with three of the most common coating polymers: pectin, alginate and chitosan. In order to evaluate the suitability of the proposed formulations, all the synthesized nanocapsules were characterized, and their cannabinoid content, size, zeta-potential, morphology and in vitro bioaccessibility was determined. Regardless of the employed cannabis source, its load and the functionalization, high cannabinoid content PLGA nanocapsules with suitable particle size and zeta-potential were obtained. Study of nanocapsules’ morphology and in vitro release assays in gastro-intestinal media suggested that high cannabis source load may compromise the structure of nanocapsules and their release properties, and hence, the use of lower content of cannabis source is recommended. Graphical Abstract

Evaluation of Pharmacokinetics of a BCS Class III Drug with Two Different Study Designs: Tenofovir Alafenamide Monofumarate Film-coated Tablet - Mustafa Arısoy; Mehtap Saydam; Yasemin Ekin Dolaksız; Özge Demirbaş; Çağrı Talay; Onursal Sağlam; Gökçe Demiray; Emel Doğan Kurtoğlu; Ayşe Nur Oktay (AAPS PharmSciTech, 2024)

Formulation and Characterization of Ethosomes for Transdermal Delivery of Prinsepia Utilis Rogle Seed Oil with Ameliorative Effects against UVB-Induced Skin Damage - Qianqian Fang; You Li; Fei Xiong; Xiaolong Hu; Ying Song; Wenbing Shen; Haijuan Dong; Xinhong Shi; Hao Wang (AAPS PharmSciTech, 2024)

Insights into Intra Periodontal Pocket Pathogenesis, Treatment, In Vitro-In Vivo Models, Products and Patents, Challenges and Opportunity - Sumel Ashique; Afzal Hussain; Tasneem Khan; Sejuti Pal; Mohd. Rihan; Arshad Farid; Thomas J. Webster; Mohd. Zaheen Hassan; Yahya I. Asiri (AAPS PharmSciTech, 2024)

Conventional vs Mechanistic IVIVC: A Comparative Study in Establishing Dissolution Safe Space for Extended Release Formulations - Sivacharan Kollipara; Tausif Ahmed; Mahendra Chougule; Chakravarthi Guntupalli; Praveen Sivadasu (AAPS PharmSciTech, 2024)

Enhanced Stability and Solidification of Volatile Eugenol by Cyclodextrin-Metal Organic Framework for Nasal Powder Delivery - Huajie Zhu; Yuting Lv; Fangyuan Xin; Manli Wang; Xiangyu Zhao; Xiaohong Ren; Jiwen Zhang; Dengke Yin; Tao Guo; Li Wu (AAPS PharmSciTech, 2024)

Formulation of Saxagliptin Oral Films: Optimization, Physicochemical Characterization, In-Vivo Assessment, and In-Vitro Real-Time Release Monitoring via a Novel Polyaniline Nanoparticles-Based Solid-Contact Screen Printed Ion-Selective Electrode - Tarek S. Makram; Sherif M. Eid; Mohamed Abu-Dahab; Mohamed H. H. AbouGhaly; Osama S. Elnahas (AAPS PharmSciTech, 2024)
Oral dispersible films have received broad interest due to fast drug absorption and no first-path metabolism, leading to high bioavailability and better patient compliance. Saxagliptin (SXG) is an antidiabetic drug that undergoes first-path metabolism, resulting in a less active metabolite, so the development of SXG oral dispersible films (SXG-ODFs) improves SXG bioavailability. The formula optimisation included a response surface experimental design and the impact of three formulation factors, the type and concentration of polymer and plasticiser concentration on in-vitro disintegration time and folding endurance. Two optimised SXG-ODFs prepared using either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose were investigated. SXG-ODFs prepared with PVA demonstrated a superior rapid disintegration time, ranging from 17 to 890 s, with the fastest disintegration time recorded at 17 s. These short durations can be attributed to the hydrophilic nature of PVA, facilitating rapid hydration and disintegration upon contact with saliva. Additionally, PVA-based films displayed remarkable folding endurance, surpassing 200 folds without rupture, indicating flexibility and stability. The high tensile strength of PVA-based films further underscores their robust mechanical properties, with tensile strength values reaching up to 4.53 MPa. SXG exhibits a UV absorption wavelength of around 212 nm, posing challenges for traditional quantitative spectrophotometric analysis, so a polyaniline nanoparticles-based solid-contact screen-printed ion-selective electrode (SP-ISE) was employed for the determination of SXG release profile effectively in comparison to HPLC. SP-ISE showed a better real-time release profile of SXG-ODFs, and the optimised formula showed lower blood glucose levels than commercial tablets. Graphical Abstract

Assembly of In-Situ Gel Containing Nano-Spanlastics of an Angiotensin II Inhibitor as a Novel Epitome for Hypertension Management: Factorial Design Optimization, In-vitro Gauging, Pharmacokinetics, and Pharmacodynamics Appraisal - Heba F. Salem; Mohamed M. Nafady; Essam M. Eissa; Hend Hassan Abdel-Sattar; Rasha A. Khallaf (AAPS PharmSciTech, 2024)
More than 1 billion people worldwide suffer from hypertension; therefore, hypertension management has been categorized as a global health priority. Losartan potassium (LP) is an antihypertensive drug with a limited oral bioavailability of about 33% since it undergoes the initial metabolic cycle. Thus, nasal administration is a unique route to overcome first-pass metabolism. The investigation focused on the potential effects of LP-loaded spanlastic vesicles (SNVs) on LP pharmacodynamics and pharmacokinetic parameters, utilizing a thin-film hydration methodology established on a 3 1 2 2 full factorial design. Entrapment efficiency (EE%) ranged from 39.8 ± 3.87.8 to 83.8 ± 2.92% for LP-SNVs. Vesicle size (VS) varied from 205.5 ± 6.5.10 to 445.1 ± 13.52 nm, and the percentage of LP released after 8 h (Q 8h ) ranged from 30.8 ± 3.10 to 68.8 ± 1.45%. LP permeated through the nasal mucosa during 24 h and flocculated from 194.1 ± 4.90 to 435.3 ± 13.53 µg/cm2. After twenty-four hours, the optimal LP-SNVs in-situ gel showed 2.35 times more permeation through the nasal mucosa than the LP solution. It also lowered systolic blood pressure, so it is thought to be better than the reference formulation in terms of pharmacodynamics. The pharmacokinetics studies demonstrated that the intranasal LP-SNVs gel boosted its bioavailability approximately 6.36 times compared to the oral LP solution. Our research showed that intranasal LP-SNVs could be a good nanoplatform because they are well-tolerated and have possible pharmacokinetics and pharmacodynamics. Graphical Abstract

Accelerative Solid-State Oxidation Behaviour of Amorphous and Partially Crystalline Venetoclax - Jesús Alberto Afonso Urich; Viktoria Marko; Katharina Boehm; Bernd Werner; Klaus Zangger; Isha Saraf; Amrit Paudel; Varun Kushwah (AAPS PharmSciTech, 2024)

Oral In-Situ Nanoplatform with Balanced Hydrophobic-Hydrophilic Property for Transport Across Gastrointestinal Mucosa - Esha S. Attar; S. Jayakumar; Padma V. Devarajan (AAPS PharmSciTech, 2024)

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation - Shagun Saini; Bindu Soni; Manjot Kaur; Shubham Thakur; Riya Shivgotra; Navid Reza Shahtaghi; Subheet Kumar Jain (AAPS PharmSciTech, 2024)

LL37 Microspheres Loaded on Activated Carbon-chitosan Hydrogel: Anti-bacterial and Anti-toxin Wound Dressing for Chronic Wound Infections - Bee-Yee Lim; Fazren Azmi; Shiow-Fern Ng (AAPS PharmSciTech, 2024)

Exploring the Potential of Artificial Intelligence as a Facilitating Tool for Formulation Development in Fluidized Bed Processor: a Comprehensive Review - Aachal A. Gosavi; Tanaji D. Nandgude; Rakesh K. Mishra; Dhiraj B. Puri (AAPS PharmSciTech, 2024)

Real-Time Particle Emission Monitoring for the Non-Invasive Prediction of Lung Deposition via a Dry Powder Inhaler - Sakiko Hatazoe; Daiki Hira; Tetsuri Kondo; Satoshi Ueshima; Tomonobu Okano; Satoshi Hamada; Susumu Sato; Tomohiro Terada; Mikio Kakumoto (AAPS PharmSciTech, 2024)
Although inhalation therapy represents a promising drug delivery route for the treatment of respiratory diseases, the real-time evaluation of lung drug deposition remains an area yet to be fully explored. To evaluate the utility of the photo reflection method (PRM) as a real-time non-invasive monitoring of pulmonary drug delivery, the relationship between particle emission signals measured by the PRM and in vitro inhalation performance was evaluated in this study. Symbicort® Turbuhaler® was used as a model dry powder inhaler. In vitro aerodynamic particle deposition was evaluated using a twin-stage liquid impinger (TSLI). Four different inhalation patterns were defined based on the slope of increased flow rate (4.9–9.8 L/s 2 ) and peak flow rate (30 L/min and 60 L/min). The inhalation flow rate and particle emission profile were measured using an inhalation flow meter and a PRM drug release detector, respectively. The inhalation performance was characterized by output efficiency (OE, %) and stage 2 deposition of TSLI (an index of the deagglomerating efficiency, St2, %). The OE × St2 is defined as the amount delivered to the lungs. The particle emissions generated by four different inhalation patterns were completed within 0.4 s after the start of inhalation, and were observed as a sharper and larger peak under conditions of a higher flow increase rate. These were significantly correlated between the OE or OE × St2 and the photo reflection signal ( p Graphical Abstract

Therapeutic Potential of Nanocarrier Mediated Delivery of Peptides for Wound Healing: Current Status, Challenges and Future Prospective - Mohit Kumar; Dikshant Kumar; Devesh Kumar; Yogesh Garg; Shruti Chopra; Amit Bhatia (AAPS PharmSciTech, 2024)

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis - Jaspreet Garg; Gargi Ghoshal; Gajanand Sharma; O. P. Katare; Sanjay Bhadada (AAPS PharmSciTech, 2024)

Optimizing Process Parameters for Controlled Drug Delivery: A Quality by Design (QbD) Approach in Naltrexone Microspheres - P. Lakshmikanth Reddy; Sangeetha Shanmugasundaram (AAPS PharmSciTech, 2024)

Exploring the Biofilm Inhibition Potential of a Novel Phytic Acid-Crosslinked Chitosan Nanoparticle: In Vitro and In Vivo Investigations - Reena Nayak; Vineet Kumar Rai; Deepak Pradhan; Jitu Halder; Tushar Kanti Rajwar; Priyanka Dash; Chandan Das; Ajit Mishra; Ritu Mahanty; Ivy Saha; Salim Manoharadas; Biswakanth Kar; et al. (AAPS PharmSciTech, 2024)

Nanocarrier – Mediated Salinomycin Delivery Induces Apoptosis and Alters EMT Phenomenon in Prostate Adenocarcinoma - Sonam Kanchan; Disha Marwaha; Bhawna Tomar; Sristi Agrawal; Sakshi Mishra; Radhika Kapoor; Sushma; Gaurav Jha; Divyansh Sharma; Rabi Sankar Bhatta; Prabhat Ranjan Mishra; Srikanta Kumar Rath (AAPS PharmSciTech, 2024)

Characterization of Freezing Processes in Drug Substance Bottles by Ice Core Sampling - Sarah S. Peláez; Hanns-Christian Mahler; Pau Rubirola Vila; Jörg Huwyler; Andrea Allmendinger (AAPS PharmSciTech, 2024)
Freezing of biological drug substance (DS) is a critical unit operation that may impact product quality, potentially leading to protein aggregation and sub-visible particle formation. Cryo-concentration has been identified as a critical parameter to impact protein stability during freezing and should therefore be minimized. The macroscopic cryo-concentration, in the following only referred to as cryo-concentration, is majorly influenced by the freezing rate, which is in turn impacted by product independent process parameters such as the DS container, its size and fill level, and the freezing equipment. (At-scale) process characterization studies are crucial to understand and optimize freezing processes. However, evaluating cryo-concentration requires sampling of the frozen bulk, which is typically performed by cutting the ice block into pieces for subsequent analysis. Also, the large amount of product requirement for these studies is a major limitation. In this study, we report the development of a simple methodology for experimental characterization of frozen DS in bottles at relevant scale using a surrogate solution. The novel ice core sampling technique identifies the axial ice core in the center to be indicative for cryo-concentration, which was measured by osmolality, and concentrations of histidine and polysorbate 80 (PS80), whereas osmolality revealed to be a sensitive read-out. Finally, we exemplify the suitability of the method to study cryo-concentration in DS bottles by comparing cryo-concentrations from different freezing protocols (-80°C vs -40°C). Prolonged stress times during freezing correlated to a higher extent of cryo-concentration quantified by osmolality in the axial center of a 2 L DS bottle. Graphical Abstract

Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats - Aaqib Javaid; Aakriti Singh; Krishana Kumar Sharma; K. A. Abutwaibe; Kanika Arora; Anurag Verma; Shyam Lal Mudavath (AAPS PharmSciTech, 2024)

Optimization of Hypericum Perforatum Microencapsulation Process by Spray Drying Method - Fadime Seyrekoğlu; Hasan Temiz; Ferda Eser; Cengiz Yıldırım (AAPS PharmSciTech, 2024)
Hypericum perforatum (HP) contains valuable and beneficial bioactive compounds that have been used to treat or prevent several illnesses. Encapsulation technology offers protection of the active compounds and facilitates to expose of the biologically active compounds in a controlled mechanism. Microcapsulation of the hydroalcoholic gum arabic and maltodextrin have hot been used as wall materials in the encapsulation of HP extract. Therefore, the optimum microencapsulation parameters of Hypericum perforatum (HP) hydroalcoholic extract were determined using response surface methodology (RSM) for the evaluation of HP extract. Three levels of three independent variables were screened using the one-way ANOVA. Five responses were monitored, including total phenolic content (TPC), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), carr index (CI), hausner ratio (HR), and solubility. Optimum drying conditions for Hypericum perforatum microcapsules (HPMs) were determined: 180 °C for inlet air temperature, 1.04/1 for ratio of maltodextrin to gum arabic (w/w), and 1.98/1 for coating to core material ratio (w/w). TPC, antioxidant activity, CI, HR, and solubility values were specified as 316.531 (mg/g GAE), 81.912%, 6.074, 1.066, and 35.017%, respectively, under the optimized conditions. The major compounds of Hypericum perforatum (hypericin and pseudohypericin) extract were determined as 4.19 μg/g microcapsule and 15.09 μg/g microcapsule, respectively. Scanning electron microscope (SEM) analysis revealed that the mean particle diameter of the HPMs was 20.36 µm. Based on these results, microencapsulation of HPMs by spray drying is a viable technique which protects the bioactive compounds of HP leaves, facilitating its application in the pharmaceutical, cosmetic, and food industries. Graphical Abstract

In Vitro In Vivo Extrapolation and Bioequivalence Prediction for Immediate-Release Capsules of Cefadroxil Based on a Physiologically-Based Pharmacokinetic ACAT Model - Najia Rahim; Syed Baqir Shyum Naqvi (AAPS PharmSciTech, 2024)

Skin- and Eco-Friendly Hand Sanitizer: A Novel Composition of Natural Extracts to Prevent the Spread of Respiratory Viruses - Marina Gomes; Isabella Dai Prá Zuchi; Catielen Paula Pavi; Gislaine Fongaro; Izabella Thaís da Silva; Bianca Ramos Pezzini (AAPS PharmSciTech, 2024)

Implications of Low-concentration Polymer on the Physical Stability of Glassy Griseofulvin: Role of the Segmental Mobility - Yanan Wang; Chai-Yee Chin; Naveen Kumar Hawala Shivashekaregowda; Qin Shi (AAPS PharmSciTech, 2024)

QbD Enabled Development and Evaluation of Pazopanib Loaded Nanoliposomes for PDAC Treatment - Aishwarya Shinde; Kanan Panchal; Parameswar Patra; Sonali Singh; Sucharitha Enakolla; Rishi Paliwal; Akash Chaurasiya (AAPS PharmSciTech, 2024)

Nanofiber-based Delivery of Luliconazole: Fabrication, Characterization, and Therapeutic Performance Assessment - Gauri Nimhan; Mahaveer Narwade; Rajesh Singh Jadon; Kavita Gajbhiye (AAPS PharmSciTech, 2024)

Verapamil-Loaded Cubosomes for Enhancing Intranasal Drug Delivery: Development, Characterization, Ex Vivo Permeation, and Brain Biodistribution Studies - Mennatullah M. Faisal; Eman Gomaa; Adel Ehab Ibrahim; Sami El Deeb; Ahmed Al-Harrasi; Tarek M. Ibrahim (AAPS PharmSciTech, 2024)
Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high E r value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution. Graphical Abstract

In-depth Mechanism, Challenges, and Opportunities of Delivering Therapeutics in Brain Using Intranasal Route - Arya Ghosh; Ankit Majie; Varnita Karmakar; Kaberi Chatterjee; Swarup Chakraborty; Manisha Pandey; Neha Jain; Suparna Roy Sarkar; Anroop B. Nair; Bapi Gorain (AAPS PharmSciTech, 2024)

HSPiP, Computational, and Thermodynamic Model–Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus-Based In Vivo Prediction in Humans: Part I - Abdul Malik; Tasneem Khan; Mohd Usman Mohd Siddique; Abdul Faruk; Ashwani Kumar Sood; Zahid Rafiq Bhat (AAPS PharmSciTech, 2024)

Silk Fibroin Formed Bioadhesive Ophthalmic Gel for Dry Eye Syndrome Treatment - Tianjiao Hao; Lu Tang; Qianzi Xu; Wei Wang; Zengjing Li; Yan Shen; Bohui Xu; Hao Luo; Qian Li; Jirong Wang; Jinling Zhang (AAPS PharmSciTech, 2024)

Phospholipid Complex Formulation Technology for Improved Drug Delivery in Oncological Settings: a Comprehensive Review - Jayesh Patil; Datta Maroti Pawde; Sankha Bhattacharya; Sauarbh Srivastava (AAPS PharmSciTech, 2024)

QbD Based Formulation Development and Optimisation of Ozenoxacin Topical Nano-Emulgel and Efficacy Evaluation Using Impetigo Mice Model - Amarnath Reddy Ramireddy; Dilip Kumar Behara (AAPS PharmSciTech, 2024)

Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment - Ei Mon Khaing; Setthapong Senarat; Kritamorn Jitrangsri; Thawatchai Phaechamud (AAPS PharmSciTech, 2024)

A Comprehensive Analysis of Biopharmaceutical Products Listed in the FDA’s Purple Book - Fuduan Chen; Hao Zhong; Ging Chan; Defang Ouyang (AAPS PharmSciTech, 2024)

Correction to: Predicting Human Dermal Drug Concentrations Using PBPK Modeling and Simulation: Clobetasol Propionate Case Study - William W. van Osdol; Jasmina Novakovic; Maxime Le Merdy; Eleftheria Tsakalozou; Priyanka Ghosh; Jessica Spires; Viera Lukacova (AAPS PharmSciTech, 2024)

The Effect of Inflammatory Bowel Disease and Irritable Bowel Syndrome on Pravastatin Oral Bioavailability: In vivo and in silico evaluation using bottom-up wbPBPK modeling - Motasem M. Alsmadi; Alla A. Abudaqqa; Nasir Idkaidek; Nidal A. Qinna; Ahmad Al-Ghazawi (AAPS PharmSciTech, 2024)

Multicomponent Amorphous Solid Forms of Telmisartan: Insights into Mechanochemical Activation and Physicochemical Attributes - Jamshed Haneef; Shakir Ali (AAPS PharmSciTech, 2024)

Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma - Kiran K. Mali; Yogeshkumar N. Gavhane; Rita D. Chakole (AAPS PharmSciTech, 2024)

Novel Drug Delivery Approaches for the Localized Treatment of Cervical Cancer - Ivy Saha; Jitu Halder; Tushar Kanti Rajwar; Ritu Mahanty; Deepak Pradhan; Priyanka Dash; Chandan Das; Vineet Kumar Rai; Biswakanth Kar; Goutam Ghosh; Goutam Rath (AAPS PharmSciTech, 2024)

Polymer Characteristics for Drug Layering on Particles Using a Novel Melt Granulation Technology, MALCORE® - Ryota Kimata; Naoki Yoshihara; Yuya Tomita; Takayuki Terukina; Hiromu Kondo (AAPS PharmSciTech, 2024)

Revolutionizing Knee Osteoarthritis Treatment: Innovative Self-Nano-Emulsifying Polyethylene Glycol Organogel of Curcumin for Effective Topical Delivery - Mahtab Baharizade; Seyed Iman Ghetmiri; Mohsen Mohammady; Soliman Mohammadi-Samani; Gholamhossein Yousefi (AAPS PharmSciTech, 2024)

On the Feasibility of Rugose Lipid Microparticles in Pressurized Metered Dose Inhalers with Established and New Propellants - Zahra Minootan; Hui Wang; Patrick Connaughton; Kellisa Lachacz; Nicholas Carrigy; Mani Ordoubadi; David Lechuga-Ballesteros; Andrew R. Martin; Reinhard Vehring (AAPS PharmSciTech, 2024)

Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient’s Compliance - Candela Juan; Loreana Gallo; Noelia Gonzalez Vidal (AAPS PharmSciTech, 2024)

Revolutionizing the Treatment of Idiopathic Pulmonary Fibrosis: From Conventional Therapies to Advanced Drug Delivery Systems - Sanskriti Singh; Sarika Wairkar (AAPS PharmSciTech, 2024)

Keratin Formed Bioadhesive Ophthalmic Gel for the Bacterial Conjunctivitis Treatment - Mengjuan Sun; Jialin Niu; Yin Zhang; Mengrong Wang; Yan Shen; Xiaolan Chen; Yujuan Mao; Qian Li (AAPS PharmSciTech, 2024)

Non-destructive Raman Method Development for Quantifying Active Pharmaceutical Ingredient in an Oral Suspension Through Plastic Dosing Syringes - Jacquelyn North; Raaidah Saari-Nordhaus; Gregory Doddridge; Madeline Seefeldt; Daniel A Young; Yemin Liu (AAPS PharmSciTech, 2024)

Minoxidil Nanosuspension-Loaded Dissolved Microneedles for Hair Regrowth - Rania Hamed; Hebah F. I. Alhadidi (AAPS PharmSciTech, 2024)

Transmucosal Delivery of Peptides and Proteins Through Nanofibers: Current Status and Emerging Developments - Priyanka Gavali; Jagruti Desai; Pranav Shah; Sujata Sawarkar (AAPS PharmSciTech, 2024)

RETRACTED ARTICLE: 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, 2024)

Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis - Bhawna Kashyap; Azhar Khan; Deepak N. Kapoor (AAPS PharmSciTech, 2024)

Film-Forming, Moisturizing, and Sensory Properties of a Cosmetic Formulation Containing Tara Gum and Brazilian Berry Extracts - Patrícia M. B. G. Maia Campos; Leticia Kakuda; Cláudia R. F. Souza (AAPS PharmSciTech, 2024)

Development of pH-Sensitive Nanoparticle Incorporated into Dissolving Microarray Patch for Selective Delivery of Methotrexate - Nur Qadri Febrianti; Anugerah Yaumil Ramadhani Aziz; Muhamad Gilang Ramadhan Tunggeng; Indianty Dwi Ramadhany; Nur Syafika; Sumayya Binti Abd Azis; Yulia Yusrini Djabir; Rangga Meidianto Asri; Andi Dian Permana (AAPS PharmSciTech, 2024)

Development and Characterization of Transdermal Patches Using Novel Thymoquinone-L-Arginine-Based Polyamide Nanocapsules for Potential Use in the Management of Psoriasis - Eman Zmaily Dahmash; Lama Murad Attiany; Dalia Ali; Shereen M. Assaf; Jamal Alkrad; Hamad Alyami (AAPS PharmSciTech, 2024)
Thymoquinone (TQ) is a phytochemical compound present in Nigella sativa and has potential benefits for treating dermatological conditions such as psoriasis. However, its clinical use is limited due to its restricted bioavailability, caused mainly by its low solubility and permeability. To overcome this, a new transdermal drug delivery system is required. Nanoparticles are known to enhance material solubility and permeability, and hence, this study aimed to synthesize TQ-loaded L -arginine-based polyamide (TQ/Arg PA) nanocapsules incorporated into transdermal patches for prolonged delivery of TQ. To achieve this, Eudragit E polymer, plasticizers, and aloe vera as penetration enhancer were used to develop the transdermal patch. Furthermore, novel TQ/Arg-PA was synthesized via interfacial polymerization, and the resultant nanocapsules (NCs) were incorporated into the matrix transdermal patch. The Arg-PA NCs’ structure was confirmed via NMR and FTIR, and optimal TQ/Arg-PA NCs containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling of TQ/Arg-PA and the transdermal patch revealed the effective development of spherical NCs with an average particle size of 129.23 ± 18.22 nm. Using Franz diffusion cells and synthetic membrane (STRAT M®), the in vitro permeation profile of the prepared patches demonstrated an extended release of TQ over 24 h, with enhanced permeation by 42.64% when aloe vera was employed. In conclusion, the produced formulation has a potential substitute for corticosteroids and other drugs commonly used to treat psoriasis due to its effectiveness, safety, and lack of the side effects typically associated with other drugs. Graphical Abstract

Sustainable Alternatives to Petroleum-Derived Excipients in Pharmaceutical Oil-in-Water Creams - Dana Gates; Abu Zayed Md Badruddoza; Md Ikhtiar Zahid; Thean Yeoh; Jaymin Shah; Taylor Walsh; Md Nurunnabi (AAPS PharmSciTech, 2024)

Development of Epigallocatechin 3-gallate-Loaded Hydrogel Nanocomposites for Oral Submucous Fibrosis - Chetan Hasmukh Mehta; Varalakshmi Velagacherla; Suman Manandhar; Yogendra Nayak; Sreedhara Ranganath K Pai; Shruthi Acharya; Usha Yogendra Nayak (AAPS PharmSciTech, 2024)
Oral submucous fibrosis (OSF) is a chronic progressive disease associated with increased collagen deposition and TGF-β1 release. The current therapy and management have been a limited success due to low efficacy and adverse drug reactions. This study aimed to evaluate epigallocatechin 3-gallate (EGCG) encapsulated nanoparticles loaded mucoadhesive hydrogel nanocomposite (HNC) for OSF. Developed HNC formulations were evaluated for their permeation behaviour using in vitro as well as ex vivo studies, followed by evaluation of efficacy and safety by in vivo studies using areca nut extract-induced OSF in rats. The disease condition in OSF-induced rats was assessed by mouth-opening and biochemical markers. The optimized polymeric nanoparticles exhibited the required particle size (162.93 ± 13.81 nm), positive zeta potential (22.50 ± 2.94 mV) with better mucoadhesive strength (0.40 ± 0.002 N), and faster permeation due to interactions of the positively charged surface with the negatively charged buccal mucosal membrane. HNC significantly improved disease conditions by reducing TGF-β1 and collagen concentration without showing toxicity and reverting the fibroid buccal mucosa to normal. Hence, the optimized formulation can be further tested to develop a clinically alternate therapeutic strategy for OSF. Graphical Abstract

Co-Processed Crystalline Solids of Ivermectin with Span® 60 as Solubility Enhancers of Ivermectin in Natural Oils - Luandri de Vos; Minja Gerber; Wilna Liebenberg; Johanna C. Wessels; Hendrik J. R. Lemmer (AAPS PharmSciTech, 2024)
Despite being discovered over five decades ago, little is still known about ivermectin. Ivermectin has several physico-chemical properties that can result in it having poor bioavailability. In this study, polymorphic and co-crystal screening was used to see if such solid-state modifications can improve the oil solubility of ivermectin. Span® 60, a lipophilic non-ionic surfactant, was chosen as co-former. The rationale behind attempting to improve oil solubility was to use ivermectin in future topical and transdermal preparations to treat a range of skin conditions like scabies and head lice. Physical mixtures were also prepared in the same molar ratios as the co-crystal candidates, to serve as controls. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The FTIR spectra of the co-crystal candidates showed the presence of Span® 60’s alkyl chain peaks, which were absent in the spectra of the physical mixtures. Due to the absence of single-crystal X-ray data, co-crystal formation could not be confirmed, and therefore these co-crystal candidates were referred to as co-processed crystalline solids. Following characterization, the solid-state forms, physical mixtures and ivermectin raw material were dissolved in natural penetration enhancers, i.e., avocado oil (AVO) and evening primrose oil (EPO). The co-processed solids showed increased oil solubility by up to 169% compared to ivermectin raw material. The results suggest that co-processing of ivermectin with Span® 60 can be used to increase its oil solubility and can be useful in the development of oil-based drug formulations. Graphical Abstract

Correction: Separable and Inseparable Silk Fibroin Microneedles for the Transdermal Delivery of Colchicine: Development, Characterization, and Comparisons - Shiji Liao; Guirong Qiu; Yanping Hu; Bohong Guo; Yuqin Qiu (AAPS PharmSciTech, 2024)

A Comprehensive Review of Hydrogel-Based Drug Delivery Systems: Classification, Properties, Recent Trends, and Applications - Huma Hameed; Saleha Faheem; Ana Cláudia Paiva-Santos; Hafiz Shoaib Sarwar; Muhammad Jamshaid (AAPS PharmSciTech, 2024)

Retraction Note: Natural Polymer–Based Graphene Oxide Bio-nanocomposite Hydrogel Beads: Superstructures with Advanced Potentials for Drug Delivery - Sadia Rehman; Asadullah Madni; Qazi Adnan Jameel; Faisal Usman; M. Rafi Raza; Faiz Ahmad; Hina Shoukat; Hamdan Aali; Afifa Shafiq (AAPS PharmSciTech, 2024)

Correction to: An in vitro Assessment of Thermo-Reversible Gel Formulation Containing Sunitinib Nanoparticles for Neovascular Age-Related Macular Degeneration - Priyanka Bhatt; Priya Narvekar; Rohan Lalani; Mahavir Bhupal Chougule; Yashwant Pathak; Vijaykumar Sutariya (AAPS PharmSciTech, 2024)

Formulation, Characterization and In Vitro Evaluation of Mesalamine and Bifidobacterium bifidum Loaded Hydrogel Beads in Capsule System for Colon Targeted Delivery - Jagtar Singh; Mohit Sharma; Harmeet Singh; Pinky Arora; Puneet Utreja; Shubham Kumar (AAPS PharmSciTech, 2024)

Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice - Kanwal Khalid; Hui Xuan Lim; Ayaz Anwar; Soon Hao Tan; Jung Shan Hwang; Seng-Kai Ong; Chit Laa Poh (AAPS PharmSciTech, 2024)

Development of Betulin-Loaded Nanostructured Lipid Carriers for the Management of Imiquimod-Induced Psoriasis - Prativa Biswasroy; Deepak Pradhan; Dilip Kumar Pradhan; Goutam Ghosh; Goutam Rath (AAPS PharmSciTech, 2024)

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology - Hao Chen; Kai Zheng; Tianshi Bu; Xin Li; Xiangyu Wang; Hao Pan (AAPS PharmSciTech, 2024)

Utilization of Lipophilic Salt and Phospholipid Complex in Lipid-Based Formulations to Modulate Drug Loading and Oral Bioavailability of Pazopanib - Karan Jadhav; Arvind Sirvi; Akash Janjal; Mahesh C. Kashyap; Abhay T. Sangamwar (AAPS PharmSciTech, 2024)

Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies - Nayera Nasser; Rania M. Hathout; Hend Abd-Allah; Omaima A. Sammour (AAPS PharmSciTech, 2024)
Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98–16.56 folds on MCF-7 and CaCo2 cells and 47.82–98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5–1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer. Graphical Abstract

Recent Trends in Nanocarrier-Based Drug Delivery System for Prostate Cancer - Amit Kumar; Akshay Kumar Lunawat; Ashutosh Kumar; Tarun Sharma; Md Moidul Islam; Milan Singh Kahlon; Debanjan Mukherjee; Raj Kumar Narang; Sarjana Raikwar (AAPS PharmSciTech, 2024)

Self-Nanoemulsion Intrigues the Gold Phytopharmaceutical Chrysin: In Vitro Assessment and Intrinsic Analgesic Effect - Samar Mohamed Elhoseny; Noha Mohamed Saleh; Mahasen Mohamed Meshali (AAPS PharmSciTech, 2024)
Chrysin is a natural flavonoid with a wide range of bioactivities. Only a few investigations have assessed the analgesic activity of chrysin. The lipophilicity of chrysin reduces its aqueous solubility and bioavailability. Hence, self-nanoemulsifying drug delivery systems (SNEDDS) were designed to overcome this problem. Kollisolv GTA, Tween 80, and Transcutol HP were selected as oil, surfactant, and cosurfactant, respectively. SNEDDS A, B, and C were prepared, loaded with chrysin (0.1%w/w), and extensively evaluated. The optimized formula (B) encompasses 25% Kollisolv GTA, 18.75% Tween 80, and 56.25% Transcutol HP was further assessed. TEM, in vitro release, and biocompatibility towards the normal oral epithelial cell line (OEC) were estimated. Brain targeting and acetic acid-induced writhing in a mouse model were studied. After testing several adsorbents, powdered SNEDDS B was formulated and evaluated. The surfactant/cosurfactant (S/CoS) ratio of 1:3 w/w was appropriate for the preparation of SNEDDS. Formula B exhibited instant self-emulsification, spherical nanoscaled droplets of 155.4 ± 32.02 nm, and a zeta potential of − 12.5 ± 3.40 mV. The in vitro release proved the superiority of formula B over chrysin suspension (56.16 ± 10.23 and 9.26 ± 1.67%, respectively). The biocompatibility of formula B towards OEC was duplicated (5.69 ± 0.03 µg/mL). The nociceptive pain was mitigated by formula B more efficiently than chrysin suspension as the writhing numbers reduced from 8.33 ± 0.96 to 0 after 60 min of oral administration. Aerosil R972 was selected as an adsorbent, and its chemical compatibility was confirmed. In conclusion, our findings prove the therapeutic efficacy of chrysin self-nanoemulsion as a potential targeting platform to combat pain. Graphical Abstract

Novel Microemulsion Containing Benzocaine and Fusidic Acid Simultaneously: Formulation, Characterization, and In Vitro Evaluation for Wound Healing - Muhammet Davut Arpa; Emre Şefik Çağlar; Dilara Güreşçi; Hande Sipahi; Neslihan Üstündağ Okur (AAPS PharmSciTech, 2024)
Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with –3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile ( p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream ( p p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations. Graphical Abstract

Innovative Nanoparticulate Strategies in Colon Cancer Treatment: A Paradigm Shift - Rati Yadav; Rohit Bhawale; Vaibhavi Srivastava; Ekta Pardhi; Harshada Anil Bhalerao; Rajesh Sonti; Neelesh Kumar Mehra (AAPS PharmSciTech, 2024)

Wurster Technology-Assisted Step-by-Step Engineering of Multi-layered Pellets (Sprinkles): Microscopy, Micro-CT, and e-Tongue-Based Analysis - Vishnu Datta Maremanda; Dirk Maertin; Malak Bitar; Abhijeet Pandey (AAPS PharmSciTech, 2024)

Nanocosmeceuticals: Trends and Recent Advancements in Self Care - Mitali Sethi; Rafquat Rana; Sharda Sambhakar; Manish K. Chourasia (AAPS PharmSciTech, 2024)

Quality-by-Design Based Development of Doxycycline Hyclate–Loaded Polymeric Microspheres for Prolonged Drug Release - Suraj Longre; Dhwani Rana; Shagun Rangra; Anil B. Jindal; Sagar Salave; Jyotsna Vitore; Derajram Benival (AAPS PharmSciTech, 2024)

Correction: Effects of Apex Size on Dissolution Profiles in the USP II Paddle Apparatus - Hiroyuki Yoshida; Tokio Morita; Yasuhiro Abe; Aoi Inagaki; Naomi Tomita; Ken-ichi Izutsu; Yoji Sato (AAPS PharmSciTech, 2024)

Nanocarrier-Mediated Drug Delivery via Inhalational Route for Lung Cancer Therapy: A Systematic and Updated Review - Nargis Ara; Abdul Hafeez (AAPS PharmSciTech, 2024)

Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations - Meenakshi Patel; Ashwini Patel; Jagruti Desai; Swayamprakash Patel (AAPS PharmSciTech, 2024)

Using Dry Dispersion Laser Diffraction to Assess Dispersibility in Spheronized Agglomerate Formulations - Faustin Arevalo; Steven Tignor; Andrew Brunskill; Adrian Goodey (AAPS PharmSciTech, 2024)

Design of floating formulations and antiulcer activity of Desmostachya bipinnata - Sanjay Kumar Putta; Koteshwara KB; Usha Y. Nayak; Sreedhara Ranganath Pai K; Raghuveer Pathuri; Aswatha Ram HN (AAPS PharmSciTech, 2024)
The study aims to design and optimize the floating formulations of the aqueous extract of Desmostachya bipinnata (ADB) to treat peptic ulcers. The trial concentrations of HPMC E50, HPMC K4M, and Carbopol 940 were used as factors, and floating lag time, total floating time, and % drug release at 12 h were used as responses. The formulation underwent evaluation for different parameters: aspirin-induced ulcers in rats assessed the antiulcer activity, and X-ray studies in rabbits evaluated the gastroretentive nature. The optimized formulation has shown a floating lag time of 32 s and floated in the gastric medium for more than 9 h with a maximum drug release of 93% at the end of 12 h by following the Korsmeyer-Peppas drug release mechanism. The optimized formulation has good flow properties. The FT-IR, DSC, and XRD studies show ADB and excipients didn't show any incompatibility. The formulation has shown significant antiulcer activity against aspirin-induced ulcers in rats, with an ulcer index of 3.38 ± 0.24 and inhibition of 76.67 ± 0.56%. The in vivo X-ray imaging proved the gastric retention of the formulations for more than 8 h. The results of the formulations demonstrate the floating ability and sustained drug release of the tablet responsible for treating peptic ulcers to show a localized effect in the gastric region and to maintain the ROS levels. Graphical Abstract

Retraction Note: Poloxamer-407-Co-Poly (2-Acrylamido-2-Methylpropane Sulfonic Acid) Cross-linked Nanogels for Solubility Enhancement of Olanzapine: Synthesis, Characterization, and Toxicity Evaluation - Kifayat Ullah Khan; Naveed Akhtar; Muhammad Usman Minhas (AAPS PharmSciTech, 2024)

Drug Nanocrystals: A Delivery Channel for Antiviral Therapies - Akanksha Chaturvedi; Swapnil Sharma; Rahul Shukla (AAPS PharmSciTech, 2024)

Development of Aerosol Dry Powder Chemotherapeutic-Loaded Microparticles for the Treatment of Lung Cancer - Ryan Ivone; Ana Karabots; Samantha A. Meenach (AAPS PharmSciTech, 2024)
Lung cancer is the leading cause of cancer-related deaths worldwide, resulting in the highest mortality rates among both men and women with respect to all other types of cancer. Difficulties in treating lung cancer arise from late-stage diagnoses and tumor heterogeneity and current treatment involves a combination of chemotherapeutics, surgery, and radiation. Chemotherapeutics administered systemically can lead to undesirable side effects and severe off-site toxicity. For example, chronic administration of the chemotherapeutic doxorubicin (DOX) leads to cardiotoxicity, thereby limiting its long-term use. Systemic administration of the highly lipophilic molecule paclitaxel (PTX) is hindered by its water solubility, necessitating the use of solubilizing agents, which can induce side effects. Thus, in this investigation, formulations consisting of spray-dried microparticles (MP) containing DOX and PTX were produced to be administered as dry powder aerosols directly to the lungs. Acetalated dextran (Ac-Dex) was used as the polymer in these formulations, as it is a biocompatible and biodegradable polymer that exhibits pH-responsive degradation. Solid-state characterization revealed that DOX and PTX remained in solubility favoring amorphous states in the MP formulations and that both drugs remained thermally stable throughout the spray drying process. In vitro release studies demonstrated the pH sensitivity of the formulations due to the use of Ac-Dex, as well as the release of both therapeutics over the course of at least 48 h. In vitro aerosol dispersion studies demonstrated that both formulations exhibited suitable aerosol dispersion properties for deep lung delivery. Graphical Abstract

Liposomal Formulation Reduces Transport and Cell Uptake of Colistin in Human Lung Epithelial Calu-3 Cell and 3D Human Lung Primary Tissue Models - Yijing Huang; Shihui Yu; Maizbha Uddin Ahmed; Qi Zhou (AAPS PharmSciTech, 2024)

Predicting Human Dermal Drug Concentrations Using PBPK Modeling and Simulation: Clobetasol Propionate Case Study - William W. van Osdol; Jasmina Novakovic; Maxime Le Merdy; Eleftheria Tsakalozou; Priyanka Ghosh; Jessica Spires; Viera Lukacova (AAPS PharmSciTech, 2024)
Quantitative in silico tools may be leveraged to mechanistically predict the dermato-pharmacokinetics of compounds delivered from topical and transdermal formulations by integrating systems of rate equations that describe permeation through the formulation and layers of skin and pilo-sebaceous unit, and exchange with systemic circulation via local blood flow. Delivery of clobetasol-17 propionate (CP) from Dermovate TM cream was simulated using the Transdermal Compartmental Absorption & Transit (TCAT TM ) Model in GastroPlus ® . The cream was treated as an oil-in-water emulsion, with model input parameters estimated from publicly available information and quantitative structure-permeation relationships. From the ranges of values available for model input parameters, a set of parameters was selected by comparing model outputs to CP dermis concentration-time profiles measured by dermal open-flow microperfusion (Bodenlenz et al . Pharm Res. 33(9):2229–38, 2016). Predictions of unbound dermis CP concentrations were reasonably accurate with respect to time and skin depth. Parameter sensitivity analyses revealed considerable dependence of dermis CP concentration profiles on drug solubility in the emulsion, relatively less dependence on dispersed phase volume fraction and CP effective diffusivity in the continuous phase of the emulsion, and negligible dependence on dispersed phase droplet size. Effects of evaporative water loss from the cream and corticosteroid-induced vasoconstriction were also assessed. This work illustrates the applicability of computational modeling to predict sensitivity of dermato-pharmacokinetics to changes in thermodynamic and transport properties of a compound in a topical formulation, particularly in relation to rate-limiting steps in skin permeation. Where these properties can be related to formulation composition and processing, such a computational approach may support the design of topically applied formulations.

The Use of Data Mining for Obtaining Deeper Insights into the Fabrication of Prednisolone-Loaded Chitosan Nanoparticles - Jehad Nasereddin; Reem Al Wadi; Ahlam Zaid Al-Kilani; Asad Abu Khalil; Mohammad Al Natour; Wael Abu Dayyih (AAPS PharmSciTech, 2024)

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation—Where Are We Now? - Hemlata Patil; Sateesh Kumar Vemula; Sagar Narala; Preethi Lakkala; Siva Ram Munnangi; Nagarjuna Narala; Miguel O. Jara; Robert O. Williams; Hibreniguss Terefe; Michael A. Repka (AAPS PharmSciTech, 2024)
Hot-melt extrusion (HME) is a globally recognized, robust, effective technology that enhances the bioavailability of poorly soluble active pharmaceutical ingredients and offers an efficient continuous manufacturing process. The twin-screw extruder (TSE) offers an extremely resourceful customizable mixer that is used for continuous compounding and granulation by using different combinations of conveying elements, kneading elements (forward and reverse configuration), and distributive mixing elements. TSE is thus efficiently utilized for dry, wet, or melt granulation not only to manufacture dosage forms such as tablets, capsules, or granule-filled sachets, but also for designing novel formulations such as dry powder inhalers, drying units for granules, nanoextrusion, 3D printing, complexation, and amorphous solid dispersions. Over the past decades, combined academic and pharmaceutical industry collaborations have driven novel innovations for HME technology, which has resulted in a substantial increase in published articles and patents. This article summarizes the challenges and models for executing HME scale-up. Additionally, it covers the benefits of continuous manufacturing, process analytical technology (PAT) considerations, and regulatory requirements. In summary, this well-designed review builds upon our earlier publication, probing deeper into the potential of twin-screw extruders (TSE) for various new applications. Graphical Abstract

Excipients for Novel Inhaled Dosage Forms: An Overview - Carol Yousry; Mimansa Goyal; Vivek Gupta (AAPS PharmSciTech, 2024)

Liquid Chromatography Tandem Mass Spectrometric Method for Quantification of Margetuximab in Rat Plasma and Application to a Pharmacokinetic Study - Pridhvi Krishna Gaddey; Raja Sundararajan (AAPS PharmSciTech, 2024)

Comparison of Properties of Acetaminophen Tablets Prepared by Wet Granulation Using Freeze-Dried Versus Phase-Inversion Bacterial Cellulose as Diluent - Sirikanya Kaewpradit; Jiraporn Chingunpitak; Wannaphorn Samhadthai; Thanyanit Suppawattana; Chutima Jantarat (AAPS PharmSciTech, 2024)

Design and Evaluation of a Dual-Sensitive In Situ Gel for the Controlled Release of Pranoprofen - Hongyu Yang; Shuihan Ding; Donghui Fan; Ziwei Zhu; Yingzhen Fan; Ji Li; Dongkai Wang (AAPS PharmSciTech, 2024)

Pharmacodynamic Studies of Pravastatin Sodium Nanoemulsion Loaded Transdermal Patch for Treatment of Hyperlipidemia - Seham I Elsayed; Marwa S El-Dahan; Germeen N. S Girgis (AAPS PharmSciTech, 2024)
Pravastatin sodium (PVS) is a hypolipidemic drug with poor oral bioavailability due to the first-pass effect. Therefore, this study aims to formulate and evaluate transdermal patches containing PVS-loaded nanoemulsions (PVS-NEs) to increase PVS’s hypolipidemic and hepatoprotective activities. PVS-NEs were prepared using the aqueous titration method, where oleic acid was chosen as an oil phase, and span 80 and tween 80 were used as surfactant and cosurfactant respectively. Droplet size (DS), polydispersity index (PDI), zeta potential (ZP), clarity, and thermodynamic stability of NEs were all characterized. Also, PVS-NEs (NE2) with 50% oil phase, 40% SC mix 2:1, and 10% water were selected as an optimum formula based on the results of DS (251 ± 16), PDI (0.4 ± 0.16), and ZP (-70 ± 10.4) to be incorporated into a transdermal patch, and PVS-NE2 loaded transdermal patches (PVS-NE2-TDPs) were prepared by solvent evaporation method. F1 patch with HPMC E15 and PVP K30 in a ratio of 3:1 represented satisfactory patch properties with good drug-excipients compatibility. Thus, it was selected as an optimum patch formula. The optimized F1 patch was characterized for thickness, moisture content, weight variation, and drug-excipients incompatibility. Therefore, it was subjected to ex vivo skin permeation and finally pharmacodynamic studies. Ex vivo permeation studies of F1 revealed that the cumulative amount of PVS permeated across rat skin was 271.66 ± 19 µg/cm 2 in 72 h, and the pharmacodynamic studies demonstrated that the F1 patch was more effective in treating hyperlipidemia than PVS-TDP (control patch) based on both blood analysis and histopathological examination. Graphical Abstract

Spray-Dried Mucoadhesive Re-dispersible Gargle of Chlorhexidine for Improved Response Against Throat Infection: Formulation Development, In Vitro and In Vivo Evaluation - Vineet Kumar Rai; Amresh Kumar; Deepak Pradhan; Jitu Halder; Tushar Kanti Rajwar; Manoj Kumar Sarangi; Priyanka Dash; Chandan Das; Salim Manoharadas; Biswakanth Kar; Goutam Ghosh; Goutam Rath (AAPS PharmSciTech, 2024)

Quercetin-Loaded Nanostructured Lipid Carrier In Situ Gel for Brain Targeting Through Intranasal Route: Formulation, In Vivo Pharmacokinetic and Pharmacodynamic Studies - Devika Sonawane; Varsha Pokharkar (AAPS PharmSciTech, 2024)

Enhanced Oral Bioavailability of Progesterone in Bilosome Formulation: Fabrication, Statistical Optimization, and Pharmacokinetic Study - Ronak Maheshwari; Lokesh Kumar Bhatt; Sarika Wairkar (AAPS PharmSciTech, 2024)

Rapidly Dissolving Trans-scleral Microneedles for Intraocular Delivery of Cyclosporine A - Hamad Alrbyawi; Manjusha Annaji; Oladiran Fasina; Srinath Palakurthi; Sai H. S. Boddu; Nageeb Hassan; Amit K. Tiwari; Amol Suryawanshi; R. Jayachandra Babu (AAPS PharmSciTech, 2024)
Cyclosporine A (CsA) is a cyclic peptide immunosuppressant drug that is beneficial in the treatment of various ocular diseases. However, its ocular bioavailability in the posterior eye is limited due to its poor aqueous solubility. Conventional CsA formulations such as a solution or emulsion permeate poorly across the eye due to various static and dynamic barriers of the eye. Dissolvable microneedle (MN)-based patches can be used to overcome barrier properties and, thus, enhance the ocular bioavailability of CsA in the posterior eye. CsA-loaded dissolvable MN patches were fabricated using polyvinylpyrrolidone (PVP) and characterized for MN uniformity and sharpness using SEM. Further characterization for its failure force, penetration force, and depth of penetration were analyzed using a texture analyzer. Finally, the dissolution time, ex vivo permeation, and ocular distribution of cyclosporine were determined in isolated porcine eyes. PVP MNs were sharp, uniform with good mechanical properties, and dissolved within 5 min. Ocular distribution of CsA in a whole porcine eye perfusion model showed a significant increase of CsA levels in various posterior segment ocular tissues as compared to a topically applied ophthalmic emulsion (Restasis®) ( P

Development of a PVA/PCL/CS-Based Nanofibrous Membrane for Guided Tissue Regeneration and Controlled Delivery of Doxycycline Hydrochloride in Management of Periodontitis: In Vivo Evaluation in Rats - Shahla Mirzaeei; Shadman Pourfarzi; Morteza Saeedi; Shiva Taghe; Ali Nokhodchi (AAPS PharmSciTech, 2024)
Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.

Changes in Tablet Color Due to Light Irradiation: Photodegradation of the Coating Polymer, Hypromellose, by Titanium Dioxide - Yuki Matsushima; Masaki Hattori; Akiko Tanaka; Tomoyuki Furubayashi; Toshiyasu Sakane (AAPS PharmSciTech, 2024)

Determining the Impact of Roller Compaction Processing Conditions on Granulate and API Properties: Impact of Formulation API Load - James Clarke; John F. Gamble; John W. Jones; Mike Tobyn; Andrew Ingram; Richard Greenwood (AAPS PharmSciTech, 2024)

Antibacterial and Antioxidant Study of New Pharmaceutical Formulation of Didecyldimethylammonium Bromide Via Pharmaceutical Deep Eutectic Solvents (PDESs) Principle - Idrees B. Qader; Aryan R. Ganjo; Hiwa O. Ahmad; Hemn A. Qader; Hewa A. Hamadameen (AAPS PharmSciTech, 2024)

Screening of Organic Small Molecule Excipients on Ternary Solid Dispersions Based on Miscibility and Hydrogen Bonding Analysis: Experiments and Molecular Simulation - Sidian Zhang; Huaqi Wang; Xiuying Zhao; Haiyan Xu; Sizhu Wu (AAPS PharmSciTech, 2024)

Targeted Nanoparticles: the Smart Way for the Treatment of Colorectal Cancer - Ahmed A. H. Abdellatif; Abdulmajeed S. Alshubrumi; Mahmoud A. Younis (AAPS PharmSciTech, 2024)

Anti-CD64 Antibody-Conjugated PLGA Nanoparticles Containing Methotrexate and Gold for Theranostics Application in Rheumatoid Arthritis - Sahil Gandhi; Pravin Shende (AAPS PharmSciTech, 2024)

In Vitro and In Vivo testing of 3D-Printed Amorphous Lopinavir Printlets by Selective Laser Sinitering: Improved Bioavailability of a Poorly Soluble Drug - Canberk Kayalar; Nada Helal; Eman M. Mohamed; Sathish Dharani; Tahir Khuroo; Mathew A. Kuttolamadom; Ziyaur Rahman; Mansoor A. Khan (AAPS PharmSciTech, 2024)

Patient In-Use Stability Testing of FDA-Approved Metformin Combination Products for N-Nitrosamine Impurity - Sathish Dharani; Eman M. Mohamed; Ziyaur Rahman; Mansoor A. Khan (AAPS PharmSciTech, 2024)

Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation - Shaaban K. Osman; Taher M. Yassin; Arafat Abdelzaher; Fatma Ahmed; Ahmed M. Mohammed; Ahmed A. H. Abdellatif; Khalid I. Saleh; Wael A. Mahdi; Sultan Alshehri; Mohamed A. El Hamd; Hatem Sarhan (AAPS PharmSciTech, 2024)

Insights into Translational and Biomedical Applications of Hydrogels as Versatile Drug Delivery Systems - Ramesh Kohar; Maitrayee Ghosh; Jyotiram A. Sawale; Amandeep Singh; Naresh Kumar Rangra; Rohit Bhatia (AAPS PharmSciTech, 2024)

Mefenamic Acid Loaded and TPGS Stabilized Mucoadhesive Nanoemulsion for the Treatment of Alzheimer’s Disease: Development, Optimization, and Brain-Targeted Delivery via Olfactory Pathway - Anmol Dogra; Ramandeep Singh Narang; Tajpreet Kaur; Jasjeet Kaur Narang (AAPS PharmSciTech, 2024)

Co-emulsified Alginate-Eudragit Nanoparticles: Potential Carriers for Localized and Time-defined Release of Tenofovir in the Female Genital Tract - Funanani Takalani; Pradeep Kumar; Pierre P. D. Kondiah; Yahya E. Choonara (AAPS PharmSciTech, 2024)
This research aimed to explore the possibilities of Eudragit S100 (ES100) and sodium alginate as carriers for tenofovir disoproxil fumarate (TDF) in the female genital tract. Alginate and alginate-ES100 nanoparticles were prepared using the ionic gelation and emulsion/gelation complexation method, respectively. The nanocarriers were tested using morphological, physicochemical, in vitro drug release, and cytotoxicity analyses. In SEM and TEM images, the presence of spherical and uniformly distributed nanoparticles was revealed. The FTIR spectrum showed that alginate and calcium chloride interacted due to ionic bonds linking divalent calcium ions and the -COO- of alginate groups. Alginate and ES100 interacted via the ester C=O amide stretching. The results obtained from XRD and DSC, on the other hand, revealed a favorable interaction between sodium alginate and ES100 polymers, as evidenced by the crystallization peaks observed. Under experimental design analysis and optimization, overall size distribution profiles ranged from 134.9 to 228.0 nm, while zeta potential results showed stable nanoparticles (−17.8 to −38.4 MV). The optimal formulation exhibited a maximum cumulative in vitro release of 72% (pH 4.2) up to 96 h. The cytotoxicity tests revealed the safety of TDF-loaded nanoparticles on vaginal epithelial cells at concentrations of 0.025 mg/mL, 0.5 mg/mL, and 1 mg/mL for 72 h. These results indicated that alginate-ES100 nanoparticles have the potential to preserve and sustain the release of the TDF drug in the FGT. The future goal is to develop a low-dose non-toxic microbicide that can be administered long term in the vagina to cater to both pregnant and non-pregnant HIV patients.

Development and Characterization of Modified Chitosan Lipopolyplex for an Effective siRNA Delivery - Shibani Supe; Archana Upadhya; Vikas Dighe; Kavita Singh (AAPS PharmSciTech, 2024)

A Quality by Design Approach for Developing SNEDDS Loaded with Vemurafenib for Enhanced Oral Bioavailability - Chakradhar JVUS; Naresh Kothuri; Sanjay Singh; Sonia Verma; Hasham Shafi; D. V. Siva Reddy; Ashwini Kedar; Rafquat Rana; Keerti Mishra; Deepak Sharma; Manish K. Chourasia (AAPS PharmSciTech, 2024)

A Rapid 3-Day Excipient Screening Methodology and its Application in Identifying Chemical Stabilizers for Solid Formulations with Mixed Mechanisms of Degradation - Amol S. Matharu; Sundeep S. Dhareshwar; Yu Cao (AAPS PharmSciTech, 2024)

A Colourful Way to Unravel the Important Fluidization-Related Granule Size Effect on Semi-Continuous Drying - Tuur Vandeputte; Michael Ghijs; Ingmar Nopens; Thomas De Beer (AAPS PharmSciTech, 2023)

Effects of Apex Size on Dissolution Profiles in the USP II Paddle Apparatus - Hiroyuki Yoshida; Tokio Morita; Yasuhiro Abe; Aoi Inagaki; Naomi Tomita; Ken-ichi Izutsu; Yoji Sato (AAPS PharmSciTech, 2023)
The use of apex vessels may solve coning problems associated with dissolution testing. However, excessive dissolution acceleration can reduce the discriminatory power. This study aimed to clarify how different apex vessel sizes affect the dissolution behavior of cone-forming formulations. Five apex vessels with different heights, centralities, and compendial vessels were used. The paddle rotation speed at which the coning phenomenon resolved was measured using standard particles of different densities. Three model formulations—USP prednisone tablets, atorvastatin calcium hydrate tablets, and levofloxacin fine granules—were selected, and dissolution tests were conducted at 30–100 revolutions per minute (rpm). Compared to the compendial vessels, the disappearance of standard particles at the apex base at lower paddle speeds in apex vessels was observed. Standard particles tended to remain in the center of the apex vessels and disappear at rotational speeds comparable to those of the compendial vessels. Dissolution increased in an apex height-dependent manner in the model formulations, except for the atorvastatin calcium hydrate tablets at 50 rpm. For levofloxacin fine granules, dissolution was also improved by reducing the paddle agitation speed to 30 rpm in the compendial vessels. Differences in apex centrality by 3 mm did not affect the dissolution rate. Our results indicate that apex vessels with low apex heights have a mount-resolving effect, but the degree of dissolution improvement by avoiding the coning phenomenon depends on the formulation characteristics used in the dissolution tests. Graphical abstract

Influence of Crystal Disorder on the Forced Oxidative Degradation of Vortioxetine HBr - Dattatray Modhave; Brenda Barrios; Jayant Iyer; Amrit Paudel (AAPS PharmSciTech, 2023)
The present study investigates the impact of the solid-state disorder of vortioxetine hydrobromide (HBr) on oxidative degradation under accelerated conditions. A range of solid-state disorders was generated via cryogenic ball milling. The solid-state properties were evaluated by calorimetry, infrared-, and Raman spectroscopies. While salt disproportionation occurred upon milling, no chemical degradation occurred by milling. The amorphous fraction remained physically intact under ambient storage conditions. Subsequently, samples with representative disordered fractions were mixed with a solid oxidative stressor (PVP-H 2 O 2 complex) and were compressed to compacts. The compacts were exposed to 40°C/75% RH for up to 6 h. The sample was periodically withdrawn and analyzed for the physical transformations and degradation. Two oxidative degradation products (DPs) were found to be formed, for which dissimilar relations to the degree of disorder and kinetics of formation were observed. The degradation rate of the major DP formation obtained by fitting the exponential model to the experimental data was found to increase up to a certain degree of disorder and decrease with a further increase in the disordered fraction. In contrast, the minor DP formation kinetics was found to increase monotonically with the increase in the disorder content. For the similar crystallinity level, the degradation trend (rate and extent) differed between the single-phase disorder generated by milling and physically mixed two-phase systems. Overall, the study demonstrates the importance of evaluating the physical and chemical (in)stabilities of the disordered solid state of a salt form of a drug substance, generated through mechano-activation. Graphical Abstract

Design and Evaluation of Ginkgolides Gastric Floating Controlled Release Tablets Based on Solid Supersaturated Self-nanoemulsifying - Kai Zheng; Jing Zhao; Qiuli Wang; Yuyang Zhao; Husheng Yang; Xinggang Yang; Lian He (AAPS PharmSciTech, 2023)

Retraction Note: In Vitro Characterization and Evaluation of the Cytotoxicity Effects of Nisin and Nisin-Loaded PLA-PEG-PLA Nanoparticles on Gastrointestinal (AGS and KYSE-30), Hepatic (HepG2) and Blood (K562) Cancer Cell Lines - Fariba Goudarzi; Asadollah Asadi; Maryam Afsharpour; Robab Hassanvand Jamadi (AAPS PharmSciTech, 2023)

Potential Applications and Additive Manufacturing Technology-Based Considerations of Mesoporous Silica: A Review - Jigar Vyas; Sudarshan Singh; Isha Shah; Bhupendra G. Prajapati (AAPS PharmSciTech, 2023)

Dissolution Profiles Comparison Using Conventional and Bias Corrected and Accelerated f2 Bootstrap Approaches with Different Software’s: Impact of Variability, Sample Size and Number of Bootstraps - Rajkumar Boddu; Sivacharan Kollipara; Adithya Karthik Bhattiprolu; Karthik Parsa; Sanketh Kumar Chakilam; Krishna Reddy Daka; Ashima Bhatia; Tausif Ahmed (AAPS PharmSciTech, 2023)

Preparation of Tetrandrine Nanocrystals by Microfluidic Method and Its In Vitro and In Vivo Evaluation - Jinping Huang; Shuwen Huang; Shengjun Liu; Lizhen Feng; Wenxiu Huang; Yao Wang; Dongyi Huang; Tingting Huang; Xingzhen Huang (AAPS PharmSciTech, 2023)

Separable and Inseparable Silk Fibroin Microneedles for the Transdermal Delivery of Colchicine: Development, Characterization, and Comparisons - Shiji Liao; Guirong Qiu; Yanping Hu; Bohong Guo; Yuqin Qiu (AAPS PharmSciTech, 2023)

In Vivo Cancer Microenvironment Responsive Glycan Receptor-Targeted Nanoparticles for Gemcitabine Delivery to Benzo[a]pyrene-Induced Lung Cancer Model - Krishan Kumar; Rinki Verma; Manjit; Priya; Mohini Mishra; Varsha Rani; Ruchi Chawla (AAPS PharmSciTech, 2023)

Evaluation of Dose-Response Relationship of Permeation Enhancer Isopropyl Myristate Release on Drug Release: Release Enhancement Efficiency and Molecular Mechanism - Jiuheng Ruan; Sida Liao; Jinye Tang; Liang Fang (AAPS PharmSciTech, 2023)

Recent Advances of Multifunctional PLGA Nanocarriers in the Management of Triple-Negative Breast Cancer - Yirivinti Hayagreeva Dinakar; Naveen Rajana; Nalla Usha Kumari; Vikas Jain; Neelesh Kumar Mehra (AAPS PharmSciTech, 2023)

Correction: Preparation of Self-microemulsion Solids of Kaempferia galanga (L.) Volatile Oil and Its Effect on Rats with Gastric Ulcer - Dongrong Liu; Ruiping Liu; Zebin Zhuang; Bijin Yao; Chuyue Qin; Fangli Ma; Jun Shi (AAPS PharmSciTech, 2023)

Correction: In Vitro and In Vivo Evaluation of Metformin Hydrochloride Hydrogels Developed with Experimental Design in the Treatment of Burns - Emine Dilek Ozyilmaz; Rojhat Celikkaya; Tansel Comoglu; Hulda Rifat Ozakpinar; Kemal Behzatoglu (AAPS PharmSciTech, 2023)

Discriminative Dissolution Method Development Through an aQbD Approach - Hongbo Chen; Rui Wang; John-David McElderry (AAPS PharmSciTech, 2023)
Using a one-factor-at-a-time approach for dissolution method and discrimination analysis can be time-consuming and may not yield the optimal and discriminative method. To address this, we have developed a two-stage workflow for the dissolution method development followed by demonstration of discrimination power through an analytical Quality by Design (aQbD) approach. In the first stage, an optimal dissolution method was achieved by determining the method operable design region (MODR) through a design of experiment study of the high-risk method-related parameters. In the second stage, we established a Formulation-Discrimination Correlation Diagram strategy to examine the method discrimination capability, through which one can determine the method discriminative design region (MDDR) and visualize the impact of each formulation parameter and their interactions on dissolution. The application of aQbD principles into a workflow provides a scientific-driven guidance for robust method development and demonstrating discrimination power for dissolution methods. Graphical Abstract

Amorphization of Low Soluble Drug with Amino Acids to Improve Its Therapeutic Efficacy: a State-of-Art-Review - Devesh U Kapoor; Sudarshan Singh; Pratishtha Sharma; Bhupendra G Prajapati (AAPS PharmSciTech, 2023)

Machine Learning-Enabled NIR Spectroscopy. Part 3: Hyperparameter by Design (HyD) Based ANN-MLP Optimization, Model Generalizability, and Model Transferability - Hussain Ali; Prakash Muthudoss; Chirag Chauhan; Ilango Kaliappan; Dinesh Kumar; Amrit Paudel; Gobi Ramasamy (AAPS PharmSciTech, 2023)
Data variations, library changes, and poorly tuned hyperparameters can cause failures in data-driven modelling. In such scenarios, model drift, a gradual shift in model performance, can lead to inaccurate predictions. Monitoring and mitigating drift are vital to maintain model effectiveness. USFDA and ICH regulate pharmaceutical variation with scientific risk-based approaches. In this study, the hyperparameter optimization for the Artificial Neural Network Multilayer Perceptron (ANN-MLP) was investigated using open-source data. The design of experiments (DoE) approach in combination with target drift prediction and statistical process control (SPC) was employed to achieve this objective. First, pre-screening and optimization DoEs were conducted on lab-scale data, serving as internal validation data, to identify the design space and control space. The regression performance metrics were carefully monitored to ensure the right set of hyperparameters was selected, optimizing the modelling time and storage requirements. Before extending the analysis to external validation data, a drift analysis on the target variable was performed. This aimed to determine if the external data fell within the studied range or required retraining of the model. Although a drift was observed, the external data remained well within the range of the internal validation data. Subsequently, trend analysis and process monitoring for the mean absolute error of the active content were conducted. The combined use of DoE, drift analysis, and SPC enabled trend analysis, ensuring that both current and external validation data met acceptance criteria. Out-of-specification and process control limits were determined, providing valuable insights into the model’s performance and overall reliability. This comprehensive approach allowed for robust hyperparameter optimization and effective management of model lifecycle, crucial in achieving accurate and dependable predictions in various real-world applications. Graphical Abstract

Nano vs Resistant Tuberculosis: Taking the Lung Route - Deepika Sharma; Pooja; Sunita Nirban; Smriti Ojha; Tarun Kumar; Neha Jain; Najwa Mohamad; Pradeep Kumar; Manisha Pandey (AAPS PharmSciTech, 2023)

The Modified Exenatide Microspheres: PLGA-PEG-PLGA Gel and Zinc-Exenatide Complex Synergistically Reduce Burst Release and Shorten Platform Stage - Wenjing Jiang; Xiangjun Gao; Qiuli Wang; Yang Chen; Dan Li; Xiaoyan Zhang; Xinggang Yang (AAPS PharmSciTech, 2023)

A Bayesian Approach to Kinetic Modeling of Accelerated Stability Studies and Shelf Life Determination - Joris Chau; Stan Altan; Anneleen Burggraeve; Hans Coppenolle; Yimer Wasihun Kifle; Hana Prokopcova; Timothy Van Daele; Hans Sterckx (AAPS PharmSciTech, 2023)

Correction: Investigations on Compaction Behavior of Kollidon®SR-Based Multi-component Directly Compressed Tablets for Preparation of Controlled Release Diclofenac Sodium - Wasfy M. Obeidat; Ishraq K. Lahlouh; Shadi F. Gharaibeh (AAPS PharmSciTech, 2023)

A Chewing Study of Abuse-Deterrent Tablets Containing Polyethylene Oxide Using a Robotic Simulator - Bangxiang Chen; Feng Zhang; Jaspreet Dhupia; Marco P. Morgenstern; Mark Costello; Heather Boyce; Wei-Jhe Sun; Saeid Raofi; Li Tian; Weiliang Xu (AAPS PharmSciTech, 2023)

In Vitro and In Vivo Evaluation of Metformin Hydrochloride Hydrogels Developed with Experimental Design in the Treatment of Burns - Emine Dilek Ozyilmaz; Rojhat Celikkaya; Tansel Comoglu; Hulda Rifat Ozakpinar; Kemal Behzatoglu (AAPS PharmSciTech, 2023)

Study on Improving the Performance of Traditional Medicine Extracts with High Drug Loading Based on Co-spray Drying Technology - Zhe Li; Wanghai Peng; Lin Zhu; Wenjun Liu; Lingyu Yang; Lihua Chen; Abid Naeem; Weifeng Zhu; Yi Feng; Liangshan Ming (AAPS PharmSciTech, 2023)

Levofloxacin–Fatty Acid Systems: Dual Enhancement Through Deep Eutectic Formation and Solubilization for Pharmaceutical Potential and Antibacterial Activity - Bayan Alkhawaja; Faisal Al-Akayleh; Jehad Nasereddin; Suzanne Abdel Malek; Nour Alkhawaja; Muhammad Kamran; Zaid Al-Rubaye; Maisa’a Smairat; Mayyas Al-Remawi; Walid Salem Aburayyan (AAPS PharmSciTech, 2023)

Preparation of Self-microemulsion Solids of Kaempferia galanga (L.) Volatile Oil and Its Effect on Rats with Gastric Ulcer - Dongrong Liu; Ruiping Liu; Zebin Zhuang; Bijin Yao; Chuyue Qin; Fangli Ma; Jun Shi (AAPS PharmSciTech, 2023)

State-of-the-Art Review of Advanced Electrospun Nanofiber Composites for Enhanced Wound Healing - Eman Abdelhakeem; Sawsan Monir; Mahmoud H. M. Teaima; Kareem Omar Rashwan; Mohamed El-Nabarawi (AAPS PharmSciTech, 2023)
Wound healing is a complex biological process with four main phases: hemostasis, inflammation, proliferation, and remodeling. Current treatments such as cotton and gauze may delay the wound healing process which gives a demand for more innovative treatments. Nanofibers are nanoparticles that resemble the extracellular matrix of the skin and have a large specific surface area, high porosity, good mechanical properties, controllable morphology, and size. Nanofibers are generated by electrospinning method that utilizes high electric force. Electrospinning device composed of high voltage power source, syringe that contains polymer solution, needle, and collector to collect nanofibers. Many polymers can be used in nanofiber that can be from natural or from synthetic origin. As such, electrospun nanofibers are potential scaffolds for wound healing applications. This review discusses the advanced electrospun nanofiber morphologies used in wound healing that is prepared by modified electrospinning techniques.

Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive In Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics - Sadia Jafar Rana; Saman Zafar; Aqeel Shahzad; Muhammad Basit; Jahanzeb Mudassir; Muhammad Akhlaq; Tahir Ali Chohan; Muhammad Sohail Arshad (AAPS PharmSciTech, 2023)

Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication - Xia Cao; Qingwen Li; Xiaoli Li; Qi Liu; Kai Liu; Tianwen Deng; Xuedi Weng; Qintong Yu; Wenwen Deng; Jiangnan Yu; Qilong Wang; Gao Xiao; et al. (AAPS PharmSciTech, 2023)