Cationic Solid SMEDDS of Efavirenz for Improved Oral Delivery: Development by Central Composite Design, In Vitro and In Vivo Evaluation - Sunil Kumar Thota; Narendar Dudhipala; Venumadhav Katla; Kishan Veerabrahma (AAPS PharmSciTech, 2023)

An Overview and Discussion of N-nitrosamine Considerations for Orally Inhaled Drug Products and Relevance to Other Dosage Forms - Hera Shams Khan; Fabienne Despres-Gnis; Cheryl L. M. Stults; James Mullis; Niran Nugara; Atish Sen; Lee Nagao (AAPS PharmSciTech, 2023)

Application of PLGA as a Biodegradable and Biocompatible Polymer for Pulmonary Delivery of Drugs - Riya Mahar; Arpita Chakraborty; Nidhi Nainwal; Richa Bahuguna; Meenakshi Sajwan; Vikash Jakhmola (AAPS PharmSciTech, 2023)

A Full Factorial Design to Optimize Aminexil Nano Lipid Formulation to Improve Skin Permeation and Efficacy Against Alopecia - Amna M. A. Makky; Eman S.El-leithy; Doaa Galaa Hussein; Abeer Khattab (AAPS PharmSciTech, 2023)

Phospholipid Complexation for Bioavailability Improvement of Albendazole: Preparation, Characterization and In Vivo Evaluation - Liyao Liu; Jinju Nie; Letao Li (AAPS PharmSciTech, 2023)

Modeling Approaches to Reimagine Stability (MARS) for Enabling Earlier Access to Critical Drugs for Patients with Unmet Medical Needs - M. Scott Furness; Hong Cai; Sithamalli Chandramouli; Mariappan Chelliah; Xiao Hong Chen; Debasis Ghosh; Shaobo Liu; Sherita McLamore; Ramnarayan Randad; Meiyu Shen (AAPS PharmSciTech, 2023)

Machine Learning–Enabled NIR Spectroscopy. Part 2: Workflow for Selecting a Subset of Samples from Publicly Accessible Data - Hussain Ali; Prakash Muthudoss; Manikandan Ramalingam; Lakshmi Kanakaraj; Amrit Paudel; Gobi Ramasamy (AAPS PharmSciTech, 2023)
An increasingly large dataset of pharmaceutics disciplines is frequently challenging to comprehend. Since machine learning needs high-quality data sets, the open-source dataset can be a place to start. This work presents a systematic method to choose representative subsamples from the existing research, along with an extensive set of quality measures and a visualization strategy. The preceding article (Muthudoss et al. . in AAPS PharmSciTech 23, 2022) describes a workflow for leveraging near infrared (NIR) spectroscopy to obtain reliable and robust data on pharmaceutical samples. This study describes the systematic and structured procedure for selecting subsamples from the historical data. We offer a wide range of in-depth quality measures, diagnostic tools, and visualization techniques. A real-world, well-researched NIR dataset was employed to demonstrate this approach. This open-source tablet dataset ( http://www.models.life.ku.dk/Tablets ) consists of different doses in milligrams, different shapes, and sizes of dosage forms, slots in tablets, three different manufacturing scales (lab, pilot, production), coating differences (coated vs uncoated), etc. This sample is appropriate; that is, the model was developed on one scale (in this research, the lab scale), and it can be great to investigate how well the top models are transferable when tested on new data like pilot-scale or production (full) scale. A literature review indicated that the PLS regression models outperform artificial neural network-multilayer perceptron (ANN-MLP). This work demonstrates the selection of appropriate hyperparameters and their impact on ANN-MLP model performance. The hyperparameter tuning approaches and performance with available references are discussed for the data under investigation. Model extension from lab-scale to pilot-scale/production scale is demonstrated. Highlights • We present a comprehensive quality metrics and visualization strategy in selecting subsamples from the existing studies • A comprehensive assessment and workflow are demonstrated using historical real-world near-infrared (NIR) data sets • Selection of appropriate hyperparameters and their impact on artificial neural network-multilayer perceptron (ANN-MLP) model performance • The choice of hyperparameter tuning approaches and performance with available references are discussed for the data under investigation • Model extension from lab-scale to pilot-scale successfully demonstrated Graphical Abstract

Assessment of Thermal and Hydrolytic Stabilities and Aqueous Solubility of Artesunate for Formulation Studies - J. W. Bezuidenhout; M. Aucamp; N. Stieger; W. Liebenberg; R. K. Haynes (AAPS PharmSciTech, 2023)

In Vivo Evaluation of Almotriptan malate Formulation through Intranasal Route for the Treatment of Migraine: Systematic Development and Pharmacokinetic Assessment - Shubham Gupta; Akhil Perla; Abhishek Roy; Jyotsna G. Vitore; Bharathi K; Sagar Salave; Dhwani Rana; Amit Sharma; Rajeshwari Rathod; Hemant Kumar; Derajram Benival (AAPS PharmSciTech, 2023)

Experimental Evaluation of the Impact of Rapid Environmental Changes on Stress Distribution in Tablet Coatings - Krishnayan Haldar; Mahesh S. Tirumkudulu; Ashwin Jain; Daniel O. Blackwood; Alfred Berchielli; Pankaj Doshi (AAPS PharmSciTech, 2022)

Metformin Hydrochloride Mucosal Nanoparticles-Based Enteric Capsule for Prolonged Intestinal Residence Time, Improved Bioavailability, and Hypoglycemic Effect - Wenjie Lu; Lingfei Yu; Lujun Wang; Songlin Liu; Manman Li; Zijun Wu; Shengqi Chen; Rongfeng Hu; Haiping Hao (AAPS PharmSciTech, 2022)

Film-Forming Properties of Topical Formulations for Skin and Hair: In Vivo and In Vitro Studies Using Biophysical and Imaging Techniques - Victor Hugo Pacagnelli Infante; Marcella Gabarra Almeida Leite; Patrícia M. B. G. Maia Campos (AAPS PharmSciTech, 2022)

Impact of Properties of Hydrated Silicon Dioxide as Core Material on the Characteristics of Drug-containing Particles Prepared by the 2-step Process Melt Granulation Technology, MALCORE® - Ryota Kimata; Naoki Yoshihara; Takayuki Terukina; Takanori Kanazawa; Hiromu Kondo (AAPS PharmSciTech, 2022)

Processability and Oral Bioavailability Improvement of Itraconazole by Particle Engineering Technique - Hiral Kapalatiya; Dhrumi Patel; Alok D. Singh; Sarika Wairkar (AAPS PharmSciTech, 2022)

A Detailed Review on Synthesis, Functionalization, Application, Challenges, and Current Status of Magnetic Nanoparticles in the Field of Drug Delivery and Gene Delivery System - Kajal Ghosal; Shreya Chatterjee; Sabu Thomas; Poulomi Roy (AAPS PharmSciTech, 2022)

Thymoquinone-Loaded Essential Oil–Based Emulgel as an Armament for Anti-psoriatic Activity - Pratik Kharat; Padakanti Sandeep Chary; Valamla Bhavana; Naveen Rajana; Geetanjali Devabattula; Chandraiah Godugu; Shashi Bala Singh; Neelesh Kumar Mehra (AAPS PharmSciTech, 2022)

Impact of Rapid Environmental Changes on Stress Distribution in Tablet Coatings: Simulations - Venugopala Swami Punati; Mahesh S. Tirumkudulu; Ashwin Jain; Daniel O. Blackwood; Alfred Berchielli; Pankaj Doshi (AAPS PharmSciTech, 2022)

Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis - Derya Arslan; Özlem Akbal Dağıstan; Olcay Sagirli; Lutfiye Mulazimoglu; Erdal Cevher; Ayca Yildiz-Pekoz (AAPS PharmSciTech, 2022)

Micro-viscoelastic Characterization of Compressed Oral Solid Dosage Forms with Ultrasonic Wave Dispersion Analysis - Tipu Sultan; Shubhajit Paul; Enamul Hasan Rozin; Yin-Chao Tseng; Michael C. F. Bazzocchi; Cetin Cetinkaya (AAPS PharmSciTech, 2022)

Dry Suspension Containing Coated Pellets with pH-Dependent Drug Release Behavior for the Taste-masking of Azithromycin - Yangyan Chen; Yang Liu; Chuanbin Wu; Xin Pan; Tingting Peng (AAPS PharmSciTech, 2022)

Self-Assembled Lipid Polymer Hybrid Nanoparticles Using Combinational Drugs for Migraine Via Intranasal Route - Preeti Dali; Pravin Shende (AAPS PharmSciTech, 2022)

Fabrication, in Vitro, and in Vivo Characterization of Mucoadhesive Berberine-Loaded Blended Wafers for Treatment of Chemotherapy-Induced Oral Mucositis - Hamed Vaezi; Shahram Rabbani; Seyed Alireza Mortazavi; Mohammad Kamalinejad; Azadeh Haeri (AAPS PharmSciTech, 2022)

An Interlaboratory Study to Identify Potential Visible Protein-Like Particle Standards - Srivalli N. Telikepalli; Michael J. Carrier; Dean C. Ripple; Greg Barnett; Ashwinkumar Bhirde; Donna Bolton; George M. Bou-Assaf; Erica Ferrari; Scott Leigh; Sophia Levitskaya-Seaman; Tim Menzen; Felix Nikels; et al. (AAPS PharmSciTech, 2022)
Visible protein-like particle standards may improve visual inspection and/or appearance testing practices used in the biotechnology industry. They may improve assay performance resulting in better alignment and more standardized training among different companies. The National Institute of Standards and Technology (NIST) has conducted an interlaboratory study to test whether the standards under development mimic typical proteinaceous particles found in biotherapeutics and if they can be implemented during the visual inspection process. Fourteen organizations from industry and government have participated. A total of 20 labs from these 14 organizations participated with analysts from 6 formulation, 7 analytical, 4 quality control, and 3 manufacturing labs. The circulated samples consisted of abraded ethylene tetrafluoroethylene (ETFE) particles or photolithographic particles. The results consist of qualitative ratings, which varied substantially among organizations and within labs. Polydisperse ETFE particle suspensions, containing particles enriched in greater than 150 µm in size, were rated more favorably than the photolithographic particles by formulation and analytical scientists. The largest monodisperse photolithographic particles (approximately 300 µm in size) were favored equally compared to ETFE by all scientists. Solution modifications to decrease the settling rate or to alter optical properties of the ETFE solutions yielded lower ratings by the analysts. Both particle types received mixed ratings for their usability and for their application for visual inspection and for training purposes. Industry feedback will assist NIST in developing reference material(s) for visible protein-like particles. Graphical Abstract

Formulation and Characterization of Oleogel as a Topical Carrier of Azithromycin - Zahraa Hasan Falhi Al-Saedi; Zainab Thabit Salih; Kawther Khalid Ahmed; Rawnak Abdulrazzak Ahmed; Sawsan Abdulraheem Jasim (AAPS PharmSciTech, 2022)

Robust Wet Milling Technique for Producing Micronized Ibuprofen Particles with Improved Solubility and Dissolution - Shahjabeen Sharif; Saiqa Muneer; Tony Wang; Emad L. Izake; Nazrul Islam (AAPS PharmSciTech, 2022)

Salix subserrata Bark Extract-Loaded Chitosan Nanoparticles Attenuate Neurotoxicity Induced by Sodium Arsenate in Rats in Relation with HPLC–PDA-ESI–MS/MS Profile - Daila I. Hamdan; Nora Tawfeek; Riham A. El-Shiekh; Heba M. A. Khalil; Mohamed Y. Mahmoud; Alaa F. Bakr; Dalia Zaafar; Nawaal Farrag; Michael Wink; Assem Mohamed El-Shazly (AAPS PharmSciTech, 2022)
Pollution is a worldwide environmental risk. Arsenic (As) is an environmental pollutant with a major health concern due to its toxic effects on multiple body organs, including the brain. Humans are exposed to As through eating contaminated food and water or via skin contact. Salix species (willow) are plants with medicinal efficacy. Salix subserrata Willd bark extract - loaded chitosan nanoparticles (SBE.CNPs) was formulated, characterized, and evaluated against As-induced neurotoxicity. The stem bark was selected for nanoparticle formulation based on HPLC–PDA-ESI–MS/MS profiling and in vitro antioxidant assessment using free radical scavenging activity. SBE.CNPs demonstrated an average un-hydrated diameter of 193.4 ± 24.5 nm and zeta potential of + 39.6 ± 0.4 mV with an encapsulation efficiency of 83.7 ± 4.3%. Compared to As-intoxicated rats, SBE.CNP-treated rats exhibited anxiolytic activity and memory-boosting as evidenced in open field test, light–dark activity box, and Y-maze. Also, it increased the antioxidant biomarkers, including superoxide dismutase and glutathione peroxidase associated with reducing the malondialdehyde levels and apoptotic activity. Besides this, SBE.CNPs maintained the brain architecture and downregulated both nuclear factor-kappa B and heme oxygenase-1 expression. These results suggest that SBE.CNP administration showed promising potent neuroprotective and antioxidative efficiencies against arsenic-induced oxidative threats.

Hot-Melt Extrusion–Based Fused Deposition Modeling 3D Printing of Atorvastatin Calcium Tablets: Impact of Shape and Infill Density on Printability and Performance - Preethi Mandati; Nagireddy Dumpa; Abdullah Alzahrani; Dinesh Nyavanandi; Sagar Narala; Honghe Wang; Suresh Bandari; Michael A. Repka; Sandip Tiwari; Nigel Langley (AAPS PharmSciTech, 2022)

Nanosizing Coamorphous Drugs Using Top-Down Approach: The Effect of Particle Size Reduction on Dissolution Improvement - Guoliang Wang; Yanchao Li; Zhiguo Qin; Tao Liu (AAPS PharmSciTech, 2022)

Biomimetic Antidote Nanoparticles: a Novel Strategy for Chronic Heavy Metal Poisoning - Hao Wang; Qing Yao; Wenquan Zhu; Yang Yang; Chunsheng Gao; Cuiyan Han; Xiaoyang Chu (AAPS PharmSciTech, 2022)

Polymer-Coated Polymeric (PCP) Microneedles for Controlled Dermal Delivery of 5-Fluorouracil - Anusha V. Matadh; Deeksha Jakka; S. G. Pragathi; Srinath Rangappa; H. N. Shivakumar; Howard Maibach; N. M. Reena; S. Narasimha Murthy (AAPS PharmSciTech, 2022)

A New Insight to Silver Sulfadiazine Antibacterial Dressings: Nanoparticle-Loaded Nanofibers for Controlled Drug Delivery - N. Başaran Mutlu-Ağardan; Serdar Tort; Şeyma Aydoğduoğlu; Merve Eylül Kıymacı (AAPS PharmSciTech, 2022)

Best Practices and Guidelines (2022) for Scale-Up and Tech Transfer in Freeze-Drying Based on Case Studies. Part 1: Challenges during Scale Up and Transfer - Serguei Tchessalov; Evgenyi Shalaev; Bakul Bhatnagar; Steven Nail; Alina Alexeenko; Feroz Jameel; Jayasree Srinivasan; Michael Dekner; Ekneet Sahni; Stefan Schneid; Petr Kazarin; Orla McGarvey; et al. (AAPS PharmSciTech, 2022)
The freeze-drying process scale-up and transfer remain a complicated and non-uniform practice. We summarized inefficient and good practices in these papers and provided some practical advice. It was demonstrated that using the same process set points/times in laboratory and commercial scale dryers may lead to loss of product quality (collapse or vial breakage). The emerging modeling approach demonstrated practical advantages. However, the upfront generation of some input parameters (vial heat transfer coefficient, minimum controllable pressure, and maximum sublimation rate) is essential for model utilization. While the primary drying step can be transferred with a high degree of confidence (e.g., using modeling), and secondary drying is usually fairly straightforward, predicting potential changes in product behavior during freezing remains challenging. Graphical Abstract

In Vitro Evaluation of Nebulized Pharmaceutical Aerosol Delivery to the Lungs Using a New Heated Dryer System (HDS) - Benjamin M. Spence; Worth Longest; Rabijit Dutta; Mohammad A. M. Momin; Sarah Strickler; Michael Hindle (AAPS PharmSciTech, 2022)

Pharmaceutical Co-crystal of Antiviral Agent Efavirenz with Nicotinamide for the Enhancement of Solubility, Physicochemical Stability, and Oral Bioavailability - Dattatraya Yadav; Jignasa Savjani; Ketan Savjani; Aakash Kumar; Snehal Patel (AAPS PharmSciTech, 2022)

Quercetin-Loaded Mesoporous Silica Nanoparticle–Based Lyophilized Tablets for Enhanced Physicochemical Features and Dissolution Rate: Formulation, Optimization, and In Vitro Evaluation - Mohammed Elmowafy; Nabil K. Alruwaili; Naveed Ahmad; Abdulsalam M. Kassem; Mohamed F. Ibrahim (AAPS PharmSciTech, 2022)

Combinatorial Approach of Thermosensitive Hydrogels and Solid Microneedles to Improve Transdermal Delivery of Valsartan: an In Vivo Proof of Concept Study - Nirmayanti Nirmayanti; Alhidayah Alhidayah; Jessica Theodor Usman; Julika Fajrika Nur; Muh. Nur Amir; Andi Dian Permana (AAPS PharmSciTech, 2022)

Fabrication of Sustained-Release Dosages Using Powder-Based Three-Dimensional (3D) Printing Technology - Bhupendra Raj Giri; Mohammed Maniruzzaman (AAPS PharmSciTech, 2022)

Enhanced Nuclear Accumulation of Doxorubicin Delivered by pH-Triggered Polydopamine-Shelled Mesoporous Silica for Chemo-Photothermal Therapy - Xiaoling Wang; Jiangyue Du; Feng Zhou; Qing Ye; Ying Chen; Dujuan Sun; Haimin Chen; Yuanyuan Lv; Xiaoyi Sun (AAPS PharmSciTech, 2022)

The Development and Evaluation of Phase Transition Microemulsion for Ocular Delivery of Acetazolamide for Glaucoma Treatment - Lubna M. Abd El Wahab; Ebtessam A. Essa; Gamal M. El Maghraby; Mona F. Arafa (AAPS PharmSciTech, 2022)
The aim of this study was to develop microemulsion (ME) formulation with possible phase transition into liquid crystals upon ocular application to enhance acetazolamide bioavailability. Pseudoternary phase diagrams were constructed using olive oil or castor oil (oily phase), Tween 80 (surfactant), and sodium carbonate solution (aqueous phase). Microemulsion and liquid crystal (LC) formulations were selected from the constructed phase diagrams and were evaluated for rheological properties and in vitro drug release. The efficacy of the developed formulations in reducing intraocular pressure (IOP) was assessed in vivo . In vitro release study showed slower release rate from LC and ME compared with drug solution with the release from LC being the slowest. Ocular application of acetazolamide ME formulations or aqueous solution resulted in significant reduction in IOP from baseline. The recorded T max values indicated faster onset of action for acetazolamide aqueous solution (1 h) compared with ME systems (3 h). However, the duration of action was prolonged and the reduction in IOP continued for up to 10 h in case of MEs, while that of aqueous solution was only for 4–5 h. The study suggested ME formulations for ocular delivery of acetazolamide with enhanced efficacy and prolonged duration of action.

Formulation, Device, and Clinical Factors Influencing the Targeted Delivery of COVID-19 Vaccines to the Lungs - Sayeed Mossadeq; Rajen Shah; Viraj Shah; Milind Bagul (AAPS PharmSciTech, 2022)

Enhanced Topical Co-delivery of Acyclovir and Lidocaine Gel Formulation Across Dermatomed Human Skin - Manjusha Annaji; Nur Mita; Shivani Rangari; Mohammed F. Aldawsari; Ahmed Alsaqr; Ishwor Poudel; Oladiran Fasina; R. Jayachandra Babu (AAPS PharmSciTech, 2022)

RETRACTED ARTICLE: 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, 2022)

Recent Advances on the Biological Study of Pharmaceutical Cocrystals - Zhipeng Wang; Yifei Xie; Mingchao Yu; Shiying Yang; Yang Lu; Guanhua Du (AAPS PharmSciTech, 2022)

Dissolution Improvement of Progesterone and Testosterone via Impregnation on Mesoporous Silica Using Supercritical Carbon Dioxide - Adejumoke Lara Ajiboye; Amélie Jacopin; Claudia Mattern; Uttom Nandi; Andrew Hurt; Vivek Trivedi (AAPS PharmSciTech, 2022)
Progesterone (PRG) and testosterone (TST) were impregnated on mesoporous silica (ExP) particles via supercritical carbon dioxide (scCO 2 ) processing at various pressures (10–18 MPa), temperatures (308.2–328.2 K), and time (30–360 min). The impact of a co-solvent on the impregnation was also studied at the best determined pressure and temperature. The properties of the drug embedded in silica particles were analysed via gas chromatography (GC), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and nitrogen adsorption. An impregnation of 1 to 82 mg/g for PRG and 0.1 to 16 mg/g for TST was obtained depending on the processing parameters. There was a significant effect of pressure, time, and co-solvent on the impregnation efficiency. Generally, an increase in time and pressure plus the use of co-solvent led to an improvement in drug adsorption. Conversely, a rise in temperature resulted in lower impregnation of both TST and PRG on ExP. There was a substantial increase in the dissolution rate (> 90% drug release within the first 2 min) of both TST and PRG impregnated in silica particles when compared to the unprocessed drugs. This dissolution enhancement was attributed to the amorphisation of both drugs due to their adsorption on mesoporous silica. Graphical Abstract

Development, Quality by Design-Based Optimization, and Stability Assessment of Oral Liquid Formulations Containing Baclofen for Hospital Use - Elisa de Saldanha Simon; Nathalie Ribeiro Wingert; Caren Gobetti; Gabriele Bordignon Primieri; Márcio Vinícius Ayres; Silvia Helena Oliveira de Almeida; Nadia Maria Volpato; Martin Steppe (AAPS PharmSciTech, 2022)

Colon-Targeted Layer-by-Layer Self-assembled Film: Pharmacokinetic Analysis of BCS Class I and Class III Model Drugs - Leela Sai Lokesh Janardhanam; Ashwini Suresh Deokar; Srivarsha Reddy Bollareddy; Venkata Vamsi Krishna Venuganti (AAPS PharmSciTech, 2022)

Insights into the Role of Compendial/Biorelevant Media on the Supersaturation Behaviour of Drug Combination (Drug-Drug Interaction) and Precipitation Inhibition by Polymers - Prachi Joshi; Abhay T. Sangamwar (AAPS PharmSciTech, 2022)

A Preliminary Pharmacodynamic Study for the Management of Alzheimer’s Disease Using Memantine-Loaded PLGA Nanoparticles - Atinderpal Kaur; Kuldeep Nigam; Amit Tyagi; Shweta Dang (AAPS PharmSciTech, 2022)

Detrimental Effects of Elevated Temperatures on the Structure and Activity of Phenylalanine Ammonia Lyase-Bovine Serum Albumin Mixtures and the Stabilizing Potential of Surfactant and Sugars - Amerh Alahmadi; Anil Dmello (AAPS PharmSciTech, 2022)

Self-Assembled Structure of α-Isostearyl Glyceryl Ether Affects Skin Permeability—a Lamellar with 70-nm Spaces and L3 Phase Enhanced the Transdermal Delivery of a Hydrophilic Model Drug - Tomohiko Sano; Akie Okada; Kazunori Kawasaki; Takuji Kume; Minoru Fukui; Hiroaki Todo; Kenji Sugibayashi (AAPS PharmSciTech, 2022)

Progesterone Phospholipid Gel for Intramuscular Administration Prepared by In Situ-Phase Separation - Ning Dong; Lihua Tang; Meihui Zhao; Yingchao Zhang; Yu Zhang; Tian Yin; Haibing He; Jingxin Gou; Yue Yuan; Xing Tang (AAPS PharmSciTech, 2022)

Proliposome-Based Nanostrategies: Challenges and Development as Drug Delivery Systems - Mangilal Choudhary; Nishtha Chaurawal; Md. Abul Barkat; Kaisar Raza (AAPS PharmSciTech, 2022)

In Vitro Study to Evaluate the Efficacy of Ultrasonicated Ethanolic Extract of Rosmarinus officinalis and its Chitosan-Based Nanoparticles Against Eimeria tenella Oocysts of Chickens - Shaimaa M. Kasem; Nabila M. Mira; Magdy E. Mahfouz; Ibrahim B. Helal (AAPS PharmSciTech, 2022)
In this study, chitosan nanoparticles (CsNPs) were used as nanocarrier for ultrasonicated ethanolic extract of Rosmarinus officinalis (UEERO) as a new nanoformulation against Eimeria tenella . Herein, CsNPs have been synthesized by ionic gelation method at pH 3 (CsNPs3) and pH 5 (CsNPs5), followed by characterization of morphology, size, polydispersity index (PDI), surface charge, and loading efficiency of UEERO. An in vitro sporulation inhibition assay (10, 5, 2.5, 1.25, 0.62, 0.31, 0.15, 0.07, 0.04, 0.02, and 0.01 mg/ml normal saline solution) against E. tenella was conducted. Results showed that free CsNPs and UEERO-CsNPs3/5 were cubic- and spherical-shaped with positive charge and average size of ~ 150.8 nm (314.4 nm) and 151.7 nm (321.1 nm), respectively. The total loading efficiency using UV–vis spectrophotometer, was 80.05 at pH 5 and 64.39% at pH 3. The in vitro sporulation inhibition assay revealed that UEERO, CsNPs3/5, and UEERO-CsNPs3/5 showed a potential inhibitory effect on sporulation (%), distortion in wall (%), and sporocyst abnormality (%) in a dose-dependent manner. Accordingly, the concentration (10 mg/ml) showed the best efficacy after 24 h in UEERO, free CsNPs, and UEERO-CsNPs. Moreover, UEERO-CsNPs3 and UEERO-CsNPs5 had stopped the sporulation (%) after 72 h. Taken all together, UEERO-CsNPs3 and UEERO-CsNPs5 are best effective against E. tenella in a dose-dependent manner in terms of sporulation (%), distortion in wall (%), and sporocysts abnormality. Graphical abstract

Exploiting Recent Trends in the Treatment of Androgenic Alopecia through Topical Nanocarriers of Minoxidil - Khushbakht Saleem; Bazla Siddiqui; Asim .ur.Rehman; Malik Mumtaz Taqi; Naveed Ahmed (AAPS PharmSciTech, 2022)

Vacuum Foam Drying Method Improved the Thermal Stability and Long-Term Shelf Life of a Live Attenuated Newcastle Disease Virus Vaccine - Fang Lyu; Yan-hong Zhao; Yu Lu; Xiao-xin Zuo; Bi-hua Deng; Min-qian Zeng; Jun-ning Wang; Ademola Olaniran; Jibo Hou; Thandeka Khoza (AAPS PharmSciTech, 2022)

Simultaneous Evaluation of Dissolution and Absorption Study of Compound Danshen Tablets and Capsules Based on Cellular Electrical Sensing Model - Lixia Ma; Yue Zhou; Jia Zhang; Xi Yuan; Yimeng Zhao; Wei Gu; Jinhuo Pan; Zhaogang Yang; Tulin Lu; Guojun Yan (AAPS PharmSciTech, 2022)

Magnetic Targeting of 5-Fluorouracil-Loaded Liposome-Nanogels for In Vivo Breast Cancer Therapy and the Cytotoxic Effects on Liver and Kidney - Damla Ulker; Rumeysa Ozyurt; Nilufer Erkasap; Vural Butun (AAPS PharmSciTech, 2022)

Thermoreversible Carbamazepine In Situ Gel for Intranasal Delivery: Development and In Vitro, Ex Vivo Evaluation - K. Mohananaidu; Bappaditya Chatterjee; Farahidah Mohamed; Syed Mahmood; Samah Hamed Almurisi (AAPS PharmSciTech, 2022)

Construction and Evaluation of Hyaluronic Acid–Coated Flurbiprofen-Layered Double Hydroxide Ocular Drug Delivery System - Donghao Gu; Hao Pan; Shuo Xu; Wenyue Chen; Renfang Zhu; Wenjing Jiang; Weisan Pan (AAPS PharmSciTech, 2022)

Particle Property Characterization and Data Curation for Effective Powder Property Modeling in the Pharmaceutical Industry - Robert C. Wadams; Ilgaz Akseli; Jacob Albrecht; Ana P. Ferreira; John F. Gamble; Michael Leane; Stephen Thomas; Yue Schuman; Lauren Taylor; Mike Tobyn (AAPS PharmSciTech, 2022)

An Application of Tumor-Associated Macrophages as Immunotherapy Targets: Sialic Acid–Modified EPI-Loaded Liposomes Inhibit Breast Cancer Metastasis - Xianmin Meng; Mingqi Wang; Kaituo Zhang; Dezhi Sui; Meng Chen; Zihan Xu; Tiantian Guo; Xinrong Liu; Yihui Deng; Yanzhi Song (AAPS PharmSciTech, 2022)

Antitumor Immunotherapy of Sialic Acid and/or GM1 Modified Coenzyme Q10 Submicron Emulsion - Xianmin Meng; Na Yan; Tiantian Guo; Meng Chen; Dezhi Sui; Mingqi Wang; Kaituo Zhang; Xinrong Liu; Yihui Deng; Yanzhi Song (AAPS PharmSciTech, 2022)

Drug-Carrier Miscibility in Solid Dispersions of Glibenclamide and a Novel Approach to Enhance Its Solubility Using an Effervescent Agent - Muralidhar Pisay; K. Vijaya Bhaskar; Chetan Hasmukh Mehta; Usha Yogendra Nayak; Kunnatur Balasundara Koteshwara; Srinivas Mutalik (AAPS PharmSciTech, 2022)
The present research aims to investigate the miscibility, physical stability, solubility, and dissolution rate of a poorly water-soluble glibenclamide (GLB) in solid dispersions (SDs) with hydrophilic carriers like PEG-1500 and PEG-50 hydrogenated palm glycerides (Acconon). Mathematical theories such as Hansen solubility parameters, Flory Huggins theory, Gibbs free energy, and the in silico molecular dynamics simulation study approaches were used to predict the drug-carrier miscibility. To increase the solubility further, the effervescence technique was introduced to the conventional solid dispersions to prepare effervescent solid dispersions (ESD). Solid dispersions (SDs) were prepared by microwave, solvent evaporation, lyophilization, and hot melt extrusion (HME) techniques and tested for different characterization parameters. The theoretical and in silico parameters suggested that GLB would show good miscibility with the selected carriers under certain conditions. Intermolecular hydrogen bonding between the drug and carrier(s) was confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. Solid-state characterizations like powder X-ray diffraction, differential scanning calorimetry, and microscopy confirm the amorphous nature of SDs. The addition of the effervescent agent improved the amorphous nature, due to which the solubility and drug release rate was increased. In vitro and ex vivo intestinal absorption studies showed improved flux and permeability than the pure drug, suggesting an enhanced drug delivery. The GLB solubility, dissolution, and stability were greatly enhanced by the SD and ESD technology. Graphical Abstract

Surface Characterization as a Tool for Identifying the Factors Affecting the Dissolution Rate of Amorphous Solid Dispersion Tablets - Dongyue Yu; Frederick Fiddler; Ahmed Ibrahim; Raymond Sanedrin; Heidi Tremblay; Stephen W. Hoag (AAPS PharmSciTech, 2022)

Effect of Texture and Surface Chemistry on Deagglomeration and Powder Retention in Capsule-Based Dry Powder Inhaler - Roman Groß; Kai Berkenfeld; Christoph Schulte; Anselm Ebert; Sunita Sule; Ameet Sule; Alf Lamprecht (AAPS PharmSciTech, 2022)
Pulmonary delivery systems should administer a high dose of the required formulation with the designated dry powder inhaler (DPI) to achieve therapeutic success. While the effects of device geometry and individual components used on powder dispersion are described in literature, potential effects of DPI surface properties on powder retention within the device and deagglomeration have not been adequately studied, but could impact inhalation therapy by modifying the available dose. For this, inner parts of a model DPI were modified by plasma treatment using various processes. Since both the hydrophilic-hydrophobic and structural properties of the surface were altered, conclusions can be drawn for future optimization of devices. The results show that surface topography has a greater influence on powder deposition and deagglomeration than hydrophilic or hydrophobic surface modification. The most important modification was observed with an increased rough surface texture in the mouth piece, resulting in lower powder deposition in this part (from 5 to 1% quantified amount of powder), without any change in powder deagglomeration compared to an untreated device. In summary, increasing the surface roughness of DPI components in the size range of a few nanometers could be an approach for future optimization of DPIs to increase the delivered dose. Graphical abstract

Evaluation of the Efficacy of Amphotericin B and Terbinafine Microemulsions and Their Combination on Cutaneous Leishmaniasis and Comparison with the Conventional Drug Form in BALB/c Mice - Zeynab Baharvandi; Anayatollah Salimi; Reza Arjmand; Ali Jelowdar; Abdollah Rafiei (AAPS PharmSciTech, 2022)

Machine Learning-Enabled NIR Spectroscopy in Assessing Powder Blend Uniformity: Clear-Up Disparities and Biases Induced by Physical Artefacts - Prakash Muthudoss; Ishan Tewari; Rayce Lim Rui Chi; Kwok Jia Young; Eddy Yii Chung Ann; Doreen Ng Sean Hui; Ooi Yee Khai; Ravikiran Allada; Manohar Rao; Saurabh Shahane; Samir Das; Irfan Babla; et al. (AAPS PharmSciTech, 2022)
NIR spectroscopy is a non-destructive characterization tool for the blend uniformity (BU) assessment. However, NIR spectra of powder blends often contain overlapping physical and chemical information of the samples. Deconvoluting the information related to chemical properties from that associated with the physical effects is one of the major objectives of this work. We achieve this aim in two ways. Firstly, we identified various sources of variability that might affect the BU results. Secondly, we leverage the machine learning-based sophisticated data analytics processes. To accomplish the aforementioned objectives, calibration samples of amlodipine as an active pharmaceutical ingredient (API) with the concentrations ranging between 67 and 133% w/w (dose ~ 3.6% w/w), in powder blends containing excipients, were prepared using a gravimetric approach and assessed using NIR spectroscopic analysis, followed by HPLC measurements. The bias in NIR results was investigated by employing data quality metrics (DQM) and bias-variance decomposition (BVD). To overcome the bias, the clustered regression (non-parametric and linear) was applied. We assessed the model’s performance by employing the hold-out and k-fold internal cross-validation (CV). NIR-based blend homogeneity with low mean absolute error and an interval estimates of 0.674 (mean) ± 0.218 (standard deviation) w/w was established. Additionally, bootstrapping-based CV was leveraged as part of the NIR method lifecycle management that demonstrated the mean absolute error (MAE) of BU ± 3.5% w/w and BU ± 1.5% w/w for model generalizability and model transferability, respectively. A workflow integrating machine learning to NIR spectral analysis was established and implemented. Graphical Abstract Impact of various data learning approaches on NIR spectral data

Correction: Self-regulated Anti-overdose Crush and Extraction-Resistant Drug Delivery System to Combat Opioid Overdose Crisis - Patel Jayendrakumar; Patel Rakesh (AAPS PharmSciTech, 2022)

Correction to: Formulation of Gelucire®-Based Solid Dispersions of Atorvastatin Calcium: In Vitro Dissolution and In Vivo Bioavailability Study - Basmah N. Aldosari; Alanood S. Almurshedi; Iman M. Alfagih; Bushra T. AlQuadeib; Mohammad A. Altamimi; Syed Sarim Imam; Afzal Hussain; Faleh Alqahtani; Ehab Elzayat; Sultan Alshehri (AAPS PharmSciTech, 2022)

Leveraging the Exploratory and Predictive Capabilities of Design of Experiments in Development of Intraarticular Injection of Imatinib Mesylate Containing Lipospheres - Amruta Gorajiya; Anita Lalwani (AAPS PharmSciTech, 2022)

Preparation of Pinocembrin-Loaded F127/MPEG-PDLLA Polymer Micelles and Anti-Osteoporotic Activity - Xia Cao; Qing He; Michael Adu-Frimpong; Xinyi Shen; Wanjing Rong; Xiaoxiao Li; Jian Zhang; Xiaoli Xia; Feng Shi; Hao Ji; Elmurat Toreniyazov; Qilong Wang; et al. (AAPS PharmSciTech, 2022)

Pharmaceutical Product Characterization and Manufacturability of Surfactant-Enriched Oil Marbles with Abiraterone Acetate - Jakub Petřík; Ondřej Rychecký; Tereza Krejčí; Lucia Becherová; Dan Trunov; Maximilián Prachár; Ondřej Navrátil; Pavel Žvátora; Lukáš Krejčík; Ondřej Dammer; Josef Beránek; Petr Kozlík; et al. (AAPS PharmSciTech, 2022)

In Vitro Permeation Studies on Carvedilol Containing Dissolving Microarray Patches Quantified Using a Rapid and Simple HPLC-UV Analytical Method - Qonita Kurnia Anjani; Akmal Hidayat Bin Sabri; Mary B. McGuckin; Huanhuan Li; Khuriah Abdul Hamid; Ryan F. Donnelly (AAPS PharmSciTech, 2022)
Analytical method validation is a vital element of drug formulation and delivery studies. Here, high-performance liquid chromatography in conjunction with UV detection (HPLC-UV) has been used to produce a straightforward, quick, yet sensitive analytical approach to quantify carvedilol (CAR). A C18 column was used to isolate the analyte from the mixture by isocratic elution with a mobile phase comprising a mixture of 0.1% v/v trifluoroacetic acid in water and acetonitrile in a ratio of 65:35 v/v at a flow rate of 0.6 mL min −1 . Linearity was observed for CAR concentrations within the range of 1.5–50 μg mL −1 ( R 2 = 0.999) in phosphate buffer saline and within the range of 0.2–6.2 μg mL −1 ( R 2 = 0.9999) in methanol. The International Council on Harmonization (ICH) requirements were followed throughout the validation of the isocratic approach, rendering it specific, accurate, and precise. Moreover, robustness tests indicated that the method remained selective and specific despite small deliberate changes to environmental and operational factors. An efficient extraction procedure was also developed to extract and quantify CAR from excised neonatal porcine skin, resulting in recovery rates ranging from 95 to 97%. The methods reported here have been successfully utilised to evaluate CAR permeation, both transdermally and intradermally following application of a dissolving microarray patch (MAP) to excised neonatal porcine skin. Graphical Abstract

Enhanced Influenza Immunity by Nasal Mucosal Administration of the TPGS-Modified Liposomal Vaccine - Shijie Ma; Rui Yu; Yaping Mai; Na Yu; Ting Gao; Jianhong Yang (AAPS PharmSciTech, 2022)

Photodegradation of Rituximab and Critical Evaluation of Its Sensibility to Electromagnetic Radiation - Víctor Pérez Medina Martínez; Miriam Cedillo Robles; Laura Carmina Juárez-Bayardo; Carlos E. Espinosa-de la Garza; Angélica Meneses; Néstor O. Pérez (AAPS PharmSciTech, 2022)

Atazanavir-Concentrate Loaded Soft Gelatin Capsule for Enhanced Concentration in Plasma, Brain, Spleen, and Lymphatics - Sheshank Sethi; Vikas Rana (AAPS PharmSciTech, 2022)

Exploiting Polymeric Films as a Multipurpose Drug Delivery System: a Review - Bruno Vincenzo Fiod Riccio; Amanda Letícia Polli Silvestre; Andreia Bagliotti Meneguin; Tais de Cassia Ribeiro; Ana Beatriz Klosowski; Priscileila Colerato Ferrari; Marlus Chorilli (AAPS PharmSciTech, 2022)

Assessment of Manufacturing Related Deficiencies for Modified Release Tablet in Abbreviated New Drug Applications - Jim Chen; Zhouxi Wang; Rakhi Shah; Anna Scherlitz; Xin Feng; Jocelyn Chen; Larisa Wu (AAPS PharmSciTech, 2022)

Cell-Penetrating Peptides as Passive Permeation Enhancers for Transdermal Drug Delivery - Lipika Chablani; Vijay Singh (AAPS PharmSciTech, 2022)

Biomaterials for Tissue Engineering Applications and Current Updates in the Field: A Comprehensive Review - Alaa Emad Eldeeb; Salwa Salah; Nermeen A. Elkasabgy (AAPS PharmSciTech, 2022)
Tissue engineering has emerged as an interesting field nowadays; it focuses on accelerating the auto-healing mechanism of tissues rather than organ transplantation. It involves implanting an In Vitro cultured initiative tissue or a scaffold loaded with tissue regenerating ingredients at the damaged area. Both techniques are based on the use of biodegradable , biocompatible polymers as scaffolding materials which are either derived from natural (e.g. alginates, celluloses, and zein) or synthetic sources (e.g. PLGA, PCL, and PLA). This review discusses in detail the recent applications of different biomaterials in tissue engineering highlighting the targeted tissues besides the in vitro and in vivo key findings. As well, smart biomaterials (e.g. chitosan) are fascinating candidates in the field as they are capable of elucidating a chemical or physical transformation as response to external stimuli (e.g. temperature, pH, magnetic or electric fields). Recent trends in tissue engineering are summarized in this review highlighting the use of stem cells, 3D printing techniques, and the most recent 4D printing approach which relies on the use of smart biomaterials to produce a dynamic scaffold resembling the natural tissue. Furthermore, the application of advanced tissue engineering techniques provides hope for the researchers to recognize COVID-19/host interaction, also, it presents a promising solution to rejuvenate the destroyed lung tissues. Graphical abstract

Continuous Processing of Micropellets via Hot-Melt Extrusion - Martin Spoerk; Ioannis Koutsamanis; Andreas Kottlan; Christian Makert; Michael Piller; Manuel Rajkovaca; Amrit Paudel; Johannes Khinast (AAPS PharmSciTech, 2022)

Self-regulated Anti-Overdose Crush and Extraction-Resistant Drug Delivery System to Combat Opioid Overdose Crisis - Patel Jayendrakumar; Patel Rakesh (AAPS PharmSciTech, 2022)

Exploration of Parteck® SRP 80 and Hypromellose for Chronomodulated Release of LTD4 Receptor Antagonist and Statistical Optimization Using Central Composite Design - Saniya Jawed; Satish CS (AAPS PharmSciTech, 2022)

The Influence of Drugs Solubilities and Chitosan-TPP Formulation Parameters on the Mean Hydrodynamic Diameters and Drugs Entrapment Efficiencies into Chitosan-TPP Nanoparticles - Wasfy M. Obeidat; Shadi F. Gharaibeh; Abdolelah Jaradat (AAPS PharmSciTech, 2022)

Self-Emulsifying Drug Delivery System Enhances Tissue Distribution of Cinnamaldehyde by Altering the Properties of the Mucus Layer - Liu Liu; Wenxuan Cao; Mengqiu Xia; Chunling Tian; Wenqing Wu; Ye Cai; Xiaoqin Chu (AAPS PharmSciTech, 2022)

A Lipid-Based In Situ-Forming Hexagonal Phase for Prolonged Retention and Drug Release in the Breast Tissue - Giovanna C. Salata; Isabella D. Malagó; Luciana B. Lopes (AAPS PharmSciTech, 2022)

IVIVC of Octreotide in PLGA-Glucose Microsphere Formulation, Sandostatin® LAR - Jin-Sook Song; So-Yeon Kim; Jae-Hyun Nam; Jaehwi Lee; Sang-Yong Song; Hasoo Seong (AAPS PharmSciTech, 2022)

Co-amorphous Drug Delivery Systems: a Review of Physical Stability, In Vitro and In Vivo Performance - Qin Shi; Yanan Wang; Sakib M. Moinuddin; Xiaodong Feng; Fakhrul Ahsan (AAPS PharmSciTech, 2022)

Formulation of Topical Flurbiprofen Solid Lipid Nanoparticle Gel Formulation Using Hot Melt Extrusion Technique - Arvind Bagde; Emmanual Kouagou; Mandip Singh (AAPS PharmSciTech, 2022)

Understanding the Effects of Associated Factors in the Development of Microsponge-Based Drug Delivery: a Statistical Quality by Design (QbD) Approach Towards Optimization - Shibam Karmakar; Sourav Poddar; Jasmina Khanam (AAPS PharmSciTech, 2022)

Fusion of Tumor-Derived Exosomes with Long-Circulating and pH-Sensitive Liposomes Loaded with Doxorubicin for the Treatment of Breast Cancer - E. R. Gomes; A. T. Carvalho; T. C. Barbosa; L. L. Ferreira; H. D. R. Calado; A. P. Sabino; M. C. Oliveira (AAPS PharmSciTech, 2022)

Development of Novel Solid Nanostructured Lipid Carriers for Bioavailability Enhancement Using a Quality by Design Approach - Neha Bajwa; Shipra Mahal; Srishti Naryal; Preet Amol Singh; Ashish Baldi (AAPS PharmSciTech, 2022)

Formulating Ternary Inclusion Complex of Sorafenib Tosylate Using β-Cyclodextrin and Hydrophilic Polymers: Physicochemical Characterization and In Vitro Assessment - Mahipal Reddy Donthi; Siva Ram Munnangi; Kowthavarapu Venkata Krishna; Sandhya Amol Marathe; Ranendra Narayan Saha; Gautam Singhvi; Sunil Kumar Dubey (AAPS PharmSciTech, 2022)

The Study of Deep Eutectic Solvent Based on Choline Chloride and l-(+)-Tartaric Acid Diethyl Ester for Transdermal Delivery System - Jianhua Lv; Xiaoyu Ou; Yaru Fang; Mi Wu; Fanghao Zheng; Lei Shang; Kaijun Lei; Yunen Liu; Yan Zhao (AAPS PharmSciTech, 2022)

Design and Development of Gastro-retentive Drug Delivery System for Trazodone Hydrochloride: a Promising Alternative to Innovator’s Controlled-Release Tablet - Manoj A. Pawar; Ganesh B. Shevalkar; Pradeep R. Vavia (AAPS PharmSciTech, 2022)

A Novel Thermal-driven Self-assembly Method to Prepare Albumin Nanoparticles: Formation Kinetics, Degradation Behavior and Formation Mechanism - Fang Li; Stacy Yeh; Qin Shi; Peng Wang; Hongyan Wu; Junbo Xin (AAPS PharmSciTech, 2022)

Continuous Manufacturing and Molecular Modeling of Pharmaceutical Amorphous Solid Dispersions - Amritha G Nambiar; Maan Singh; Abhishek R Mali; Dolores R Serrano; Rajnish Kumar; Anne Marie Healy; Ashish Kumar Agrawal; Dinesh Kumar (AAPS PharmSciTech, 2022)

Optimization of Meloxicam Solid Dispersion Formulations for Dissolution Enhancement and Storage Stability Using 33 Full Factorial Design Based on Response Surface Methodology - Maha F. Emam; Ahmed A. El-Ashmawy; Nadia M. Mursi; Laila H. Emara (AAPS PharmSciTech, 2022)
This study aimed to formulate and optimize solid-dispersion of meloxicam (MX) employing response-surface-methodology (RSM). RSM allowed identification of the main effects and interactions between studied factors on MX dissolution and acceleration of the optimization process. 3 3 full factorial design with 27 different formulations was proposed. Effects of drug loading percentage (A), carriers’ ratio (B), method of preparation (C), and their interactions on percent MX dissolved after 10 and 30 min (Q 10min & Q 30min ) from fresh and stored samples were studied in distilled water. The considered levels were 2.5%, 5.0%, and 7.5% (factor A), three ratios of Soluplus®/Poloxamer-407 (factor B). Physical mixture (PM), fusion method (FM), and hot-melt-extrusion (HME) were considered factor (C). Stability studies were carried out for 3 months under stress conditions. The proposed optimization design was validated by 3-extra checkpoints formulations. The optimized formulation was selected via numerical optimization and investigated by DSC, XRD, PLM, and in vitro dissolution study. Results showed that HME technique gave the highest MX dissolution rate compared to other techniques (FM & PM). At constant level of factor (C), the amount of MX dissolved increased by decreasing MX loading and increasing Soluplus in carriers’ ratio. Actual responses of the optimized formulation were in close consistency with predicted data. Amorphous form of MX in the optimized formulation was proved by DSC, XRD, and PLM. Selected factors and their levels of the optimization design were significantly valuable for demonstrating and adapting the expected formulation characteristics for rapid dissolution of MX (Q 10min = 89.09%) from fresh and stored samples. Graphical abstract

In Situ Forming Chitosan-Alginate Interpolymer Complex Bioplatform for Wound Healing and Regeneration - Hillary Mndlovu; Pradeep Kumar; Lisa C. du Toit; Yahya E. Choonara (AAPS PharmSciTech, 2022)

Visual Monitoring of Disintegration of Solid Oral Dosage Forms in Simulated Gastric Fluids Using Low-Field NMR Imaging - Qianyu Ye; Meilai Ding; Ping Zhang; Peng Wu; Yong Wang; Cordelia Selomulya; Xiao Dong Chen (AAPS PharmSciTech, 2022)

Correction: Environmental Monitoring for Closed Robotic Workcells Used in Aseptic Processing: Data to Support Advanced Environmental Monitoring Strategies - Joseph McCall; Nonita Barnard; Kevin Gadient; Chandra Kasireddy; Adara Kurtz; Yiwei Li; Thomas Page; Tadd Putnam; Áine Brennan (AAPS PharmSciTech, 2022)

Foam-Based Drug Delivery: A Newer Approach for Pharmaceutical Dosage Form - Mohit Kumar; Anil Thakur; Uttam Kumar Mandal; Ashish Thakur; Amit Bhatia (AAPS PharmSciTech, 2022)

Retraction Note: Hyaluronic Acid-Pluronic®F127-Laden Soft Contact Lenses for Corneal Epithelial Healing: In Vitro and In Vivo Studies - Ning Wei; Xianghui Xu; Chao Huang; Lijun Cao (AAPS PharmSciTech, 2022)

Antidepressant and Cardioprotective Effects of Self-Nanoemulsifying Self-Nanosuspension Loaded with Hypericum perforatum on Post-Myocardial Infarction Depression in Rats - Heba M. A. Khalil; Dina B. Mahmoud; Riham A. El-Shiekh; Alaa F. Bakr; Amira A. Boseila; Sally Mehanna; Reham A. Naggar; Hesham A. Eliwa (AAPS PharmSciTech, 2022)
Hypericum perforatum (HP) is characterized by potent medicinal activity. However, the poor water solubility of many HP constituents limits their therapeutic effectiveness. Self-nanoemulsifying self-nanosuspension loaded with HP (HP.SNESNS) was formulated to improve the bioefficacy of HP. It was prepared using 10% triacetin, 57% Tween 20, and 33% PEG 400 and then incorporated with HP extract (100 mg/mL). HP.SNESNS demonstrated a bimodal size distribution (258.65 ± 29.35 and 9.08 ± 0.01 nm) corresponding to nanosuspension and nanoemulsion, respectively, a zeta potential of -8.03 mV, and an enhanced dissolution profile. Compared to the unformulated HP (100 mg/kg), HP.SNESNS significantly improved cardiac functions by decreasing the serum myocardial enzymes, nitric oxide (NO), and tumor necrosis factor- α (TNF-α) as well as restoring the heart tissue's normal architecture. Furthermore, it ameliorates anxiety, depressive-like behavior, and cognitive dysfunction by decreasing brain TNF-α, elevating neurotransmitters (norepinephrine and serotonin), and brain-derived neurotrophic factor (BDNF). In addition, HP.SNESNS augmented the immunohistochemical expression of cortical and hippocampal glial fibrillary acidic protein (GFAP) levels while downregulating the cortical Bcl-2-associated X protein (Bax) expression levels. Surprisingly, these protective activities were comparable to the HP (300 mg/kg). In conclusion, HP.SNESNS (100 mg/kg) exerted antidepressant and cardioprotective activities in the post-MI depression rat model. Graphical Abstract

Meropenem-Loaded Nanostructured Lipid Carriers For Skin and Soft Tissue Infection Caused by Staphylococcus aureus: Formulation, Design, and Evaluation - Kshipra Rajpoot; Shiv Kumar Prajapati; Akanksha Malaiya; Richa Jain; Aakanchha Jain (AAPS PharmSciTech, 2022)

Development of a Nanoformulation for Oral Protein Administration: Characterization and Preclinical Orofacial Antinociceptive Effect - Marina de Barros Mamede Vidal Damasceno; Sacha Aubrey Alves Rodrigues Santos; João Ronielly Campêlo Araújo; Lana Karine Vasconcelos Barroso; Samara Casemiro Benevides; Francisco Ernani Alves Magalhães; Kaio César Simiano Tavares; Renato de Azevedo Moreira; Ana Cristina de Oliveira Monteiro-Moreira; Angelo Roncalli Alves e Silva; Adriana Rolim Campos (AAPS PharmSciTech, 2022)

Correction to: Effect of Lipid Vehicles on Solubility, Stability, and Topical Permeation of Delta-9-Tetrahydrocannabinol - Vijay Kumar Shankar; Abhishek Shettar; Srinath Rangappa; Inayet Ellis; Masumi Dave; Reena Murthy; S. Narasimha Murthy (AAPS PharmSciTech, 2022)

Determination of BET Specific Surface Area of Hydrate-Anhydrate Systems Susceptible to Phase Transformation Using Inverse Gas Chromatography - Minhthi Bui; Karthik Nagapudi; Paroma Chakravarty (AAPS PharmSciTech, 2022)

Fabrication of TPGS-Grafted Polyamidoamine Dendrimer for Enhanced Piperine Brain Delivery and Pharmacokinetics - Ajit Singh; Akshada Mhaske; Rahul Shukla (AAPS PharmSciTech, 2022)

Development of Inline Near-Infrared Spectroscopy Method for Real-Time Monitoring of Blend Uniformity of Direct Compression and Granulation-Based Products at Commercial Scales - Aruna Khanolkar; Bhaskar Patil; Viraj Thorat; Gautam Samanta (AAPS PharmSciTech, 2022)

Enzyme Responsive Delivery of Anti-Retroviral Peptide via Smart Hydrogel - Taj Yeruva; Chi H. Lee (AAPS PharmSciTech, 2022)

Lipid- and TPGS-Based Core–Shell-Type Nanocapsules Endowed with High Paclitaxel Loading and Enhanced Anticancer Potential - Sameer S. Katiyar; Ravindra Patil; Rohan Ghadi; Kaushik Kuche; Varun Kushwah; Chander Parkash Dora; Sanyog Jain (AAPS PharmSciTech, 2022)

Impact of Extractables/Leachables from Filter Materials on the Stability of Protein-Based Pharmaceutical Products - Varun Kushwah; Juliana Münzer; Verena Feenstra; Stefan Mohr; Amrit Paudel (AAPS PharmSciTech, 2022)
The manufacturing of biopharmaceutical drug solutions can involve close contact with various polymeric components, including common filter membranes. Potential leachable substances from filters may interact with the protein and thereby increase the structural damage and aggregation. The main aim of the study deals with the assessment of extractable and leachable (E/L) from different filters and the potential effect of E/Ls on protein (human granulocyte-colony stimulating factor (rh-GCSF) stability. The present study examines the E/L profile of five different polymeric filter membranes using various chromatographic techniques including LC–MS and GC–MS. In order to investigate their effect on protein stability, G-CSF (human granulocyte colony-stimulating factor) formulations were spiked with filter leachable stock solutions at two different pH levels. The spiked formulations were further analyzed with respect to their aggregation behavior. The results demonstrated a higher E/L content in the case of polyamide (PA), polycarbonate (PC), and polyethersulfone (PES) filters as compared to the polytetrafluoroethylene (PTFE) and regenerative cellulose (RC) filter materials. The E/L from RC and PES was found surface-active, whereas E/L from PA and RC significantly altered the particle size/structure resulting in the aggregation of proteins. Furthermore, bisphenol A was found to be one of the E/L substances from PC filters and can impose significant health problems when administered along with pharmaceutical products. The present study reports a qualitative rank ordering of the filter membranes in terms of their propensity to generate E/Ls and thus can be helpful in selecting a suitable membrane filter.

Fixed Dose Combination Tablets of Aripiprazole and Divalproex Sodium: a Pilot Pharmacokinetic Study in Human Volunteers - Zia Ahmed; Fazal Subhan; Saba Ahmed (AAPS PharmSciTech, 2022)

Retraction Note: Bimatoprost Imprinted Silicone Contact Lens to Treat Glaucoma - Feng Yan; Yanxia Liu; Shulan Han; Qingsong Zhao; Nannan Liu (AAPS PharmSciTech, 2022)

Mannose-Anchored Nano-Selenium Loaded Nanostructured Lipid Carriers of Etravirine for Delivery to HIV Reservoirs - Satish Rojekar; Leila Fotooh Abadi; Rohan Pai; Mahendra Kumar Prajapati; Smita Kulkarni; Pradeep R. Vavia (AAPS PharmSciTech, 2022)

Evaluation of EDTA Dianhydride Versus Diphenyl Carbonate Nanosponges for Curcumin - Hadeia Mashaqbeh; Rana Obaidat; Nizar A. Al-shar’i (AAPS PharmSciTech, 2022)

Alleviating the Influence of Circadian Rhythms and Drug Properties to the Release of Paliperidone Gel Matrix Tablets with Compression Coating Technology and Microenvironment Shaping - Zherui Zhang; Shumin Chen; Man Wen; Haibing He; Yu Zhang; Tian Yin; Jingxin Gou; Xing Tang (AAPS PharmSciTech, 2022)

Antileishmanial Agents Co-loaded in Transfersomes with Enhanced Macrophage Uptake and Reduced Toxicity - Fatima Zahid; Sibgha Batool; Fakhar ud-Din; Zakir Ali; Muhammad Nabi; Salman Khan; Omer Salman; Gul Majid Khan (AAPS PharmSciTech, 2022)

Correction to: The Study of Ginger-Derived Extracellular Vesicles as a Natural Nanoscale Drug Carrier and Their Intestinal Absorption in Rats - Fulong Man; Chen Meng; Yang Liu; Yuchen Wang; Yun Zhou; Jinqian Ma; Rong Lu (AAPS PharmSciTech, 2022)

Retraction Note: Risedronate-Loaded Macroporous Gel Foam Enriched With Nanohydroxyapatite: Preparation, Characterization, and Osteogenic Activity Evaluation Using Saos-2 Cells - Nadia M. Morsi; Rehab Nabil Shamma; Nouran Osama Eladawy; Abdelfattah A. Abdelkhalek (AAPS PharmSciTech, 2022)

Effect of Lipid Vehicles on Solubility, Stability, and Topical Permeation of Delta-9-Tetrahydrocannabinol - Vijay Kumar Shankar; Abhishek Shettar; Srinath Rangappa; Inayet Ellis; Masumi Dave; Reena Murthy; S. Narasimha Murthy (AAPS PharmSciTech, 2022)

Application of the Non-dominated Sorting Genetic Algorithm II in Multi-objective Optimization of Orally Disintegrating Tablet Formulation - Jiaqi Zhang; Yu Yao; Wei Sun; Liling Tang; Xiaodong Li; Huaqing Lin (AAPS PharmSciTech, 2022)

Retraction Note to: Sustained Delivery of Timolol Using Nanostructured Lipid Carriers-Laden Soft Contact Lenses - Chenfei Tian; Lu Zeng; Le Tang; Jingni Yu; Mei Ren (AAPS PharmSciTech, 2022)

Evaluation of Manufacturer-to-Manufacturer Variability of Croscarmellose Sodium: Influence on the Dissolution of Sitagliptin Tablets (Water-Soluble Drug) and Escitalopram Tablets (Sparingly Soluble Drug) - Arash Yavari; Mostafa Saffary; Ali Nokhodchi; Seyed Kazem Sadjady (AAPS PharmSciTech, 2022)

β-Cyclodextrin-Grafted Chitosan Enhances Intestinal Drug Absorption and Its Preliminary Mechanism Exploration - Linghui Zou; Zhongbin Zhang; Jinqing Chen; Xu Yang; Yuyang Li; Jing Tang; Xiaolu Du; Ling Tang; Dan Liang; Xiaoyong Zhu; Jianfang Feng; Wenya Ding (AAPS PharmSciTech, 2022)

Hydroxypropyl Beta Cyclodextrin as a Potential Surface Modifier for Paclitaxel Nanocrystals - Razan Haddad; Nasr Alrabadi; Bashar Altaani; Majed Masadeh; Tonglei Li (AAPS PharmSciTech, 2022)

Correction: Mucus-Penetrating Alginate-Chitosan Nanoparticles Loaded with Berberine Hydrochloride for Oral Delivery to the Inflammation Site of Ulcerative Colitis - Lingfeng Sun; Xiangjiang Nie; Wenjie Lu; Qing Zhang; Wenyou Fang; Song Gao; Shengqi Chen; Rongfeng Hu (AAPS PharmSciTech, 2022)

Retraction Note: Ofloxacin‑Loaded Niosome‑Laden Contact Lens: Improved Properties of Biomaterial for Ocular Drug Delivery - Jiayong Liu; Xue Wang (AAPS PharmSciTech, 2022)

5-Aminolevulinic Acid-Hyaluronic Acid Complexes Enhance Skin Retention of 5-Aminolevulinic Acid and Therapeutic Efficacy in the Treatment of Hypertrophic Scar - Liya Yang; Huihui Deng; Yiman Chen; Yuling Chen; Ling Guo; Min Feng (AAPS PharmSciTech, 2022)

Environmental Monitoring for Closed Robotic Workcells Used in Aseptic Processing: Data to Support Advanced Environmental Monitoring Strategies - Joseph McCall; Nonita Barnard; Kevin Gadient; Chandra Kasireddy; Adara Kurtz; Yiwei Li; Thomas Page; Tadd Putnam; Áine Brennan (AAPS PharmSciTech, 2022)
The human operator is acknowledged as the greatest potential source of contamination in aseptic processing. To avoid contamination, barrier systems have progressively reduced the amount of human intervention in the critical zone. This study extends the trajectory of enhanced patient safety through the elimination of human intervention in aseptic filling. Eight companies that are users of closed robotic workcells have aggregated their usage data from 2018 to 2021. The study analyzes the critical design elements and performance of the Cytiva SA25 Aseptic Filling Workcell. The SA25 is a standardized, fully closed robotic system for aseptic filling of vials, syringes, and cartridges that eliminates operator intervention in the critical zone. The standardized design means that the system is not modified to suit a particular application and the same environmental monitoring strategy can be used across different installations. The SA25 provides significantly increased sterility assurance when producing sterile injectables. Users have observed non-viable particle levels well within ISO 5/Grade A air requirements, with extremely low probabilities of entering a dosage container. There have been zero cases of microbial growth in more than 250 media fills and good manufacturing practice (GMP) batches. Across all dosage formats and sizes, the aseptic process is repeatable, with more than 99.3% of units meeting acceptance criteria. These data demonstrate that eliminating risk through design is successful in the SA25, with an improved aseptic process in comparison to filling systems using Restricted Access Barrier Systems (RABS) or isolators with glove ports. One of the contributing companies to this article achieved an industry first. The U.S. FDA-approved commercial production of their biologic drugs without the requirement for routine viable environmental monitoring (EM), requiring viable EM only during process simulations. Based on the data presented and planned future research, new regulatory consideration should be made for closed robotic workcells to ensure that regulations meant for previous technologies with different risk profiles are not inappropriately applied. Graphical abstract

Preparation and Evaluation of Siderol Amorphous Solid Dispersions: Selection of Suitable Matrix/Carrier - Maria Koromili; Afroditi Kapourani; Antigoni Koletti; George Papandreou; Andreana N. Assimopoulou; Diamanto Lazari; Panagiotis Barmpalexis (AAPS PharmSciTech, 2022)

Development and Characterization of Celecoxib Solid Self-nanoemulsifying Drug Delivery Systems (S-SNEDDS) Prepared Using Novel Cellulose-Based Microparticles as Adsorptive Carriers - Fabian-Pascal Schmied; Alexander Bernhardt; Victor Baudron; Birte Beine; Sandra Klein (AAPS PharmSciTech, 2022)
Self-nanoemulsifying drug delivery systems (SNEDDS) represent an interesting platform for improving the oral bioavailability of poorly soluble lipophilic drugs. While Liquid-SNEDDS (L-SNEDDS) effectively solubilize the drug in vivo , they have several drawbacks, including poor storage stability. Solid-SNEDDS (S-SNEDDS) combine the advantages of L-SNEDDS with those of solid dosage forms, particularly stability. The aim of the present study was to convert celecoxib L-SNEDDS into S-SNEDDS without altering their release behavior. Various commercially available adsorptive carrier materials were investigated, as well as novel cellulose-based microparticles prepared by spray drying from an aqueous dispersion containing Diacel ® 10 and methyl cellulose or gum arabic as a binder prior to their use. Particle size and morphology of the carrier materials were screened by scanning electron microscopy and their effects on the loading capacity for L-SNEDDS were investigated, and comparative in vitro dissolution studies of celecoxib L-SNEDDS and the different S-SNEDDS were performed immediately after preparation and after 3 months of storage. Among the adsorptive carrier materials, the novel cellulose-based microparticles were found to be the most suitable for the preparation of celecoxib S-SNEDDS from L-SNEDDS, enabling the preparation of a solid, stable formulation while preserving the in vitro release performance of the L-SNEDDS formulation.

Sorbitan Monolaurate–Containing Liposomes Enhance Skin Cancer Cell Cytotoxicity and in Association with Microneedling Increase the Skin Penetration of 5-Fluorouracil - Luiziana Cavalcante Costa Fernandes Crisóstomo; Genuína Stephanie Guimarães Carvalho; Luzia Kalyne Almeida Moreira Leal; Tamara Gonçalves de Araújo; Karina Alexandre Barros Nogueira; Durcilene Alves da Silva; Fábio de Oliveira Silva Ribeiro; Raquel Petrilli; Josimar O. Eloy (AAPS PharmSciTech, 2022)

Micro-fluidic Spray Freeze Dried Ciprofloxacin Hydrochloride-Embedded Dry Powder for Inhalation - Yingjie Chen; Shen Yan; Shengyu Zhang; Quanyi Yin; Xiao Dong Chen; Winston Duo Wu (AAPS PharmSciTech, 2022)

Formulation and Evaluation of Eudragit® RL Polymeric Double Layer Films for Prolonged-Release Transdermal Delivery of Tamsulosin Hydrochloride - Shereen M. Assaf; Aya M. Ghanem; Shayma’a A. Alhaj; Enam A. Khalil; AlSayed Alarabi Sallam (AAPS PharmSciTech, 2022)

Determination of Alteration in Micromeritic Properties of a Solid Dispersion: Brunauer-Emmett-Teller Based Adsorption and Other Structured Approaches - Lovepreet Singh; Lakhvir Kaur; Gurjeet Singh; R. K. Dhawan; Manjeet Kaur; Navdeep Kaur; Prabhpreet Singh (AAPS PharmSciTech, 2022)

Evaluation of Emulsifying Ability of Phospholipids by Langmuir Monolayers and Stability of High Oil Ratio O/W Emulsions - Shanghui Li; Bing Zhang; Minsi Chang; Ruirong Zhang; Bei Liu; Tian Yin; Yu Zhang; Haibing He; Jingxin Gou; Yanjiao Wang; Xing Tang (AAPS PharmSciTech, 2022)

Advanced Vesicular Systems for Antifungal Drug Delivery - Shaimaa Mosallam; Rofida Albash; Manar Adel Abdelbari (AAPS PharmSciTech, 2022)
Fungal infections are considered one of the most serious conditions as their occurrence has increased lately. Fungi like Candida , Fusarium , and Aspergillus species mostly affect immunocompromised patients as they are considered opportunistic pathogens. These infections can be superficial, cutaneous, subcutaneous, or systemic fungal infections that require specific treatment. There is a wide variety of antifungal drugs that can be used to cure fungal infections; however, most of them have many systemic side effects due to their physicochemical characteristics and high toxicity profile. Hence, the current review focuses on various advanced vesicular carriers with high biocompatibility that can encapsulate the antifungal drugs owing to increase their efficacy and limit the undesirable side effects. These advanced systems can manage stability, solubility, bioavailability, safety, and effectiveness issues present in conventional systems.

Nanoparticle Engineering of Aprepitant Using Nano-by-Design (NbD) Approach - Pratik Kakade; Zubiya Pathan; Sandip Gite; Amit Mirani; Vandana B. Patravale (AAPS PharmSciTech, 2022)

Construction and Evaluation of Traceable rhES-QDs-M-MS Protein Delivery System: Sustained-Release Properties, Targeted Effect, and Antitumor Activity - Xiaowen Wu; Yi Zou; Kunyu Du; Yi Du; Caleb Kesse Firempong; Yang Yu; Haibing He; Hongfei Liu; Changshan Sun (AAPS PharmSciTech, 2022)

Design of a Personalized Nasal Device (Matrix-Piston Nasal Device, MPD) for Drug Delivery: a 3D-Printing Application - Ioanna-Maria Menegatou; Paraskevi Papakyriakopoulou; Dimitrios M. Rekkas; Paraskevas Dallas; Georgia Valsami (AAPS PharmSciTech, 2022)

Convolution- and Deconvolution-Based Approaches for Prediction of Pharmacokinetic Parameters of Diltiazem Extended-Release Products in Flow-Through Cell Dissolution Tester - Nesrin F. Taha; Laila H. Emara (AAPS PharmSciTech, 2022)
The present study evaluated the effect of different configuration setups of the Flow-Through Cell (USP IV) dissolution tester in developing in vitro–in vivo correlation (IVIVC). A Biopharmaceutics Classification System (BCS) Class I Diltiazem (DTZ), formulated in extended-release (ER) gel-matrix system, was employed for this purpose. The study also assessed the validity and predictability of IVIVC employing both deconvolution- and convolution-based approaches. In vitro release was conducted in USP IV as open- or closed-loop setups, while the pharmacokinetic (PK) data were obtained from a previous fasted-state cross-over study conducted on 8 healthy male volunteers, after oral administration of ER matrix tablets against market product (Tildiem Retard® 90 mg). PK parameters (C max , AUC 0-t and AUC 0-∞ ) were predicted, and compared with actual data to establish the strength of correlation models. Results showed that DTZ release from ER products was influenced by operating the FTC in different configuration-setups, where ≥ 75% of labeled DTZ was released after 6 h and 12 h using the open- and closed-loop settings, respectively. Correlation between fraction-dissolved versus fraction-absorbed for both ER products displayed linear relation upon employing FTC open-loop setup. Convolution-based approach was more discriminative in predicting DTZ in vivo PK parameters with a minimal prediction error, compared to deconvolution-based approach. A successful trial to predict DTZ PKs from individual in vitro data performed in USP IV dissolution model was established, employing convolution technique. Basic principle of the convolution approach provides a simple and practical method for developing IVIVC, hence could be utilized for other BCS Class I extended-release drug products. Graphical abstract

Modeling of In Vitro Dissolution Profiles of Carvedilol Immediate-Release Tablets in Different Dissolution Media - Duygu Yilmaz Usta; Tuba Incecayir (AAPS PharmSciTech, 2022)

Evaluation of Alternative Metallic Stearates as Lubricants in Pharmaceutical Tablet Formulation - Dongyue Yu; Haichen Nie (AAPS PharmSciTech, 2022)

Dissolution of a Biopharmaceutics Classification System Class II Free Acid from Immediate Release Tablets Containing a Microenvironmental pH Modulator: Comparison of a Biorelevant Bicarbonate Buffering System with Phosphate Buffers - Dorota Haznar-Garbacz; Dagmara Hoc; Grzegorz Garbacz; Marek Lachman; Daria Słomińska; Michał Romański (AAPS PharmSciTech, 2022)
Poor water dissolution of active pharmaceutical ingredients (API) limits the rate of absorption from the gastrointestinal tract. Increasing the pH of a solid form microenvironment can enhance the dissolution of weakly acidic drugs, but data on this phenomenon in a physiologically relevant bicarbonate media are lacking. In this paper, we examined the effect of a microenvironmental pH modulator (Na 2 HPO 4 ) on the dissolution of a Biopharmaceutics Classification System (BCS) class II free weak acid (ibuprofen) at biorelevant conditions, including an automatic bicarbonate buffering system, as well as in compendial (50 mM) and low-concentration (10 mM) phosphate buffers with no external pH control. The tablets of 200 mg ibuprofen with either Na 2 HPO 4 (phosphate formulation, PF) or NaCl (reference formulation, RF) were manufactured using a compression method. In a pH 2 simulated gastric fluid, only PF produced a transient supersaturation of ibuprofen, dissolving a fourfold higher drug amount than RF. In a bicarbonate-buffered simulated intestinal fluid with a dynamically controlled pH (5.7, 7.2, and 5.8 to 7.7 gradient), PF dissolved more drug within 30 min than RF ( p ≤ 0.019). Of note, the use of a 50 mM phosphate buffer pH 7.2 provided opposite results—RF dissolved the API much faster than PF. Moreover, 10 mM phosphate buffers of pH 5.6 and 7.2 could neither maintain a constant pH nor mimic the bicarbonate buffer performance. In conclusion, the use of a bicarbonate-buffered intestinal fluid, instead of phosphate buffers, may be essential in dissolution tests of BCS class II drugs combined with pH modulators. Graphical abstract

Evaluation of an Anhydrous Permeation-Enhancing Vehicle for Percutaneous Absorption of Hormones - Guiyun Song; Daniel Banov; Hui Song; Yi Liu; Kendice Ip; August S. Bassani; Benigno C. Valdez (AAPS PharmSciTech, 2022)

Preparation and Evaluation of a Microsponge Dermal Stratum Corneum Retention Drug Delivery System for Griseofulvin - Lin Ma; Song Guo; Jingshu Piao; Mingguan Piao (AAPS PharmSciTech, 2022)

Betamethasone Dipropionate Nanocrystals: Investigation, Feasibility and In Vitro Evaluation - Viral Patel; Tejal A. Mehta (AAPS PharmSciTech, 2022)

Additive Manufacturing of Solid Products for Oral Drug Delivery Using Binder Jetting Three-Dimensional Printing - Yingya Wang; Anette Müllertz; Jukka Rantanen (AAPS PharmSciTech, 2022)

Alpha Tocopherol Loaded Polymeric Nanoparticles: Preparation, Characterizations, and In Vitro Assessments Against Oxidative Stress in Spinal Cord Injury Treatment - Aayushi Laliwala; Amita Daverey; Sandeep K. Agrawal; Alekha K. Dash (AAPS PharmSciTech, 2022)

A Novel Preparation Method for Effervescent Tablets of Xianganfang Containing Fresh Juice using a Semi-Solid Extrusion 3D Printer with Three Cartridge Holders - Xiangru Dong; Wenfang Zhang; Xiaoting Wang; Sijia Liu; Jiawei Liang; Chunqiao Liufu; Shaofeng Zeng; Jiali Pang; Siting Li; Lingjuan Xiong; Guoyan Zhou; Weixing Zhu; et al. (AAPS PharmSciTech, 2022)

Fabrication and Characterization of Buccal Film Loaded Self-emulsifying Drug Delivery System containing Lysiphyllum strychnifolium Stem Extracts - Wiwat Pichayakorn; Chaowalit Monton; Yupaporn Sampaopan; Kamon Panrat; Jirapornchai Suksaeree (AAPS PharmSciTech, 2022)

A High-Throughput LC-MS/MS Method for the Simultaneous Quantification of Twenty-Seven Drug Molecules in Ocular Tissues - Brock Matter; David W. A. Bourne; Uday B. Kompella (AAPS PharmSciTech, 2022)

Factors Limiting the Translatability of Rodent Model–Based Intranasal Vaccine Research to Humans - Lucy Cai; Haiyue Xu; Zhengrong Cui (AAPS PharmSciTech, 2022)

Retraction Note: Oral Bioavailability Improvement of Tailored Rosuvastatin Loaded Niosomal Nanocarriers to Manage Ischemic Heart Disease: Optimization, Ex Vivo and In Vivo Studies - Qiang Liu; Jing Xu; Kun Liao; Na Tang (AAPS PharmSciTech, 2022)

Particle Design and Inhalation Delivery of Iodine for Upper Respiratory Tract Infection Therapy - Kaikai Zhang; Xiaohong Ren; Jiacai Chen; Caifen Wang; Siyu He; Xiaojin Chen; Ting Xiong; Jiawen Su; Shujun Wang; Weifeng Zhu; Jiwen Zhang; Li Wu (AAPS PharmSciTech, 2022)

Development of a Novel Bilosomal System for Improved Oral Bioavailability of Sertraline Hydrochloride: Formulation Design, In Vitro Characterization, and Ex Vivo and In Vivo Studies - Aliaa Ismail; Mohammed Teiama; Basma Magdy; Wedad Sakran (AAPS PharmSciTech, 2022)
This study was proposed to develop an optimized sertraline hydrochloride (SER)–loaded bilosomal system and evaluate its potential for enhancement of drug oral bioavailability. A full 2 3 factorial design was used to prepare SER-loaded bilosomal dispersions by thin film hydration using span 60, cholesterol (CHL), and sodium deoxycholate (SDC). The investigated factors included the total concentration of span 60 and CHL ( X 1 ), span 60:CHL molar ratio ( X 2 ), and SER:SDC molar ratio ( X 3 ). The studied responses were entrapment efficiency ( EE %) ( Y 1 ), zeta potential ( Y 2 ), particle size ( Y 3 ), and in vitro % drug released at 2 ( Y 4 ), 8 ( Y 5 ), and 24 h ( Y 6 ). The selected optimal bilosomal dispersion (N1) composition was 0.5% w/v ( X 1 ), 1:1 ( X 2 ), and 1:2 ( X 3 ). Then, N1 was freeze dried into FDN1 that compared with pure SER for in vitro drug release, ex vivo permeation through rabbit intestine, and in vivo absorption in rats. Moreover, storage effect on FDN1 over 3 months was assessed. The optimal dispersion (N1) showed 68 ± 0.7% entrapment efficiency, − 41 ± 0.78 mV zeta potential, and 377 ± 19 nm particle size. The freeze-dried form (FDN1) showed less % drug released in simulated gastric fluids with remarkable sustained SER release up to 24 h compared to pure SER. Moreover, FDN1 showed good stability, fivefold enhancement in SER permeation through rabbit intestine, and 222% bioavailability enhancement in rats’ in vivo absorption study compared to pure SER. The SER-loaded bilosomal system (FDN1) could improve SER oral bioavailability with minimization of gastrointestinal side effects. Graphical abstract

Nanoencapsulation of Tea Catechins for Enhancing Skin Absorption and Therapeutic Efficacy - Ibrahim A. Aljuffali; Chih-Hung Lin; Shih-Chun Yang; Ahmed Alalaiwe; Jia-You Fang (AAPS PharmSciTech, 2022)

Visible Particle Identification Using Raman Spectroscopy and Machine Learning - Han Sheng; Yinping Zhao; Xiangan Long; Liwen Chen; Bei Li; Yiyan Fei; Lan Mi; Jiong Ma (AAPS PharmSciTech, 2022)

Using Tiny-TIM Dissolution and In Silico Simulation to Accelerate Oral Product Development of a BCS Class II Compound - Laibin Luo; Naveen K. Thakral; Robert Schwabe; Li Li; Shirlynn Chen (AAPS PharmSciTech, 2022)

Risk Assessment and QbD-Based Optimization of Sorafenib Tosylate Colon Targeted Bilayer Tablet: In Vitro Characterization, In Vivo Pharmacokinetic, and In Vivo Roentgenography Studies - Prathmesh Kenjale; Varsha Pokharkar (AAPS PharmSciTech, 2022)

Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line - Abdelrahman Y. Sherif; Gamaleldin I. Harisa; Fars K. Alanazi; Fahd A. Nasr; Ali S. Alqahtani (AAPS PharmSciTech, 2022)

Formulation and Physicochemical and Biological Characterization of Etoposide-Loaded Submicron Emulsions with Biosurfactant of Sophorolipids - Xiaojing Ma; Tong Wang; Zequan Yu; Junqian Shao; Jun Chu; Huixia Zhu; Risheng Yao (AAPS PharmSciTech, 2022)

Clove Oil Endorsed Transdermal Flux of Dronedarone Hydrochloride Loaded Bilosomal Nanogel: Factorial Design, In vitro Evaluation and Ex vivo Permeation - Mahmoud H. Teaima; Jihad Mahmoud Alsofany; Mohamed A. El-Nabarawi (AAPS PharmSciTech, 2022)
The goal of this study was to develop a bilosomal gel formulation to enhance transdermal permeability of dronedarone hyrdrochloride (DRN) which suffers from poor oral absorption and limited bioavailability. To overcome this obstacle, bilosomes were successfully prepared using 2 3 full-factorial design. Span®40, cholesterol, sodium deoxycholate (bile salt), clove oil (permeability enhancer), and either Tween® 60 or Tween® 80 (edge activator) were used in bilosome preparation by ethanol injection method. In this design, independent variables were X1, edge activator type; X2, edge activator amount (mg); and X3, permeability enhancer concentration (% w/v). Optimal formula (B2) of the highest desirability of (0.776) demonstrated minimum vesicle size (VS) of 312.4 ± 24.42 nm, maximum absolute value of zeta potential (ZP) − 36.17 ± 2.57 mV, maximum entrapment efficiency (EE %) of 80.95 ± 3.01%, maximum deformability Index (DI) of 8.24 ± 1.26 g and maximum drug flux after 12 h ( J 12 ) of 21.23 ± 1.54 µg/cm 2 h upon ex vivo permeation study. After 12 h, 70.29 ± 6.46% of DRN was released from B2. TEM identification of B2 showed spherical shaped nanosized vesicles which were physically stable for 3 months at different temperatures. B2 was incorporated into carboxymethylcellulose gel base for easiness of dermal application. B2 gel demonstrated good physical properties, non-Newtonian psuedoplastic flow, and enhanced release (57.0 ± 8.68% of DRN compared to only 13.3 ± 1.2% released from drug suspension after 12 h) and enhanced skin permeation. Graphical abstract

Semisolid Extrusion 3D Printing of Propranolol Hydrochloride Gummy Chewable Tablets: an Innovative Approach to Prepare Personalized Medicine for Pediatrics - Chunxiao Zhu; Yang Tian; Enhui Zhang; Xiang Gao; Hui Zhang; Nan Liu; Xiaolu Han; Yong Sun; Zengming Wang; Aiping Zheng (AAPS PharmSciTech, 2022)

Correction: Oxidative Stability in Lipid Formulations: A Review of the Mechanisms, Drivers, and Inhibitors of Oxidation - Jasmine Musakhanian; Jean-David Rodier; Masumi Dave (AAPS PharmSciTech, 2022)

Dry Powder Inhalers Based on Chitosan-Mannitol Binary Carriers: Effect of the Powder Properties on the Aerosolization Performance - Ziyu Zhao; Guanlin Wang; Zhengwei Huang; Ying Huang; Hangping Chen; Xin Pan; Xuejuan Zhang (AAPS PharmSciTech, 2022)

Chitosan-Coated Liposomes: The Strategy to Reduce Intestinal Toxicity and Improve Bioavailability of Oral Vinorelbine - Chen Guo; Xichun Zhu; Haoyang Yuan; Haoyu Liu; Yu Zhang; Tian Yin; Haibing He; Jingxin Gou; Xing Tang (AAPS PharmSciTech, 2022)

Formulation and Pharmacokinetic Evaluation of Ethyl Cellulose/HPMC-Based Oral Expandable Sustained Release Dosage of Losartan Potassium - Taha Umair Wani; Abdul Aala Fazli; Syed Naiem Raza; Nisar Ahmad Khan; Faheem A. Sheikh (AAPS PharmSciTech, 2022)

Development and Optimization of Osimertinib-loaded Biodegradable Polymeric Nanoparticles Enhance In-vitro Cytotoxicity in Mutant EGFR NSCLC Cell Models and In-vivo Tumor Reduction in H1975 Xenograft Mice Models - Sanjay Kumar K; Asha deepti Choppala (AAPS PharmSciTech, 2022)

Correction to: Fabrication of Three-Dimensional Bioactive Composite Scaffolds for Hemostasis and Wound Healing - Divya Tripathi; Arpit Sharma; Priyanka Tyagi; Chandra Shekhar Beniwal; Gaurav Mittal; Abhinav Jamini; Harpal Singh; Amit Tyagi (AAPS PharmSciTech, 2022)

Ionic Liquids Assisted Topical Drug Delivery for Permeation Enhancement: Formulation Strategies, Biomedical Applications, and Toxicological Perspective - Prerana D. Navti; Abhijeet Pandey; Ajinkya Nitin Nikam; Bharath Singh Padya; Guruprasad Kalthur; Kunnatur B. Koteshwara; Srinivas Mutalik (AAPS PharmSciTech, 2022)
Topical drug delivery provides several benefits over other conventional routes by providing localizing therapeutic effects and also avoids the gastrointestinal tract circumventing the first-pass metabolism and enzymatic drug degradation. Being painless, the topical route also prevents the difficulties linked with the parenteral route. However, there are limitations to the current topical systems which necessitate the need for further research to find functional excipients to overcome these limitations. This review deals in depth with the ionic liquids concerning their physicochemical properties and applicability as well as their role in the arena of topical drug delivery in permeation enhancement, bioavailability enhancement of the drugs by solvation, and drug moiety modification. The review gives a detailed insight into the recent literature on ionic liquid–based topical formulations like ionic liquid–based emulsions, active pharmaceutical ingredient-ionic liquids, ionic liquid–based bacterial cellulose membranes, topical small interfering RNA (siRNA) delivery, and ionogels as a possible solutions for overcoming the challenges associated with the topical route. This review also takes into account the toxicological aspects and biomedical applications of ionic liquids. Graphical Abstract

SIRT 1 Activator Loaded Inhaled Antiangiogenic Liposomal Formulation Development for Pulmonary Hypertension - Sagar Dhoble; Vandana Patravale (AAPS PharmSciTech, 2022)

Gastroretentive Sustained-Release Tablets Combined with a Solid Self-Micro-Emulsifying Drug Delivery System Adsorbed onto Fujicalin® - Yoshihiro Omachi (AAPS PharmSciTech, 2022)

Development of Optimized Sumatriptan–Prochlorperazine Combined Orodispersible Films Without Disintegrant: in vitro, ex vivo and in vivo Characterization - Sana Javed; Amjad Hussain; Pervaiz Akhtar Shah; Syed Atif Raza; Ubaid Ullah Anwer; Rahat Shamim; Fatima Rasool; Muhammad Ahsan Hafiz; Nadeem Irfan Bukhari (AAPS PharmSciTech, 2022)

Correction to: Puerarin-Loaded PLGA Nanoparticles: Optimization Processes of Preparation and Anti-Alcohol Intoxication Effects in Mice - Qin Han; Kejie Chen; Cunli Su; Xin Liu; Xiaoming Luo (AAPS PharmSciTech, 2022)

Correction to: Co-spray Drying Drugs with Aqueous Polymer Dispersions (APDs)—a Systematic Review - Nizar Al-Zoubi; Ioannis Partheniadis; Ahmad Aljaberi; Ioannis Nikolakakis (AAPS PharmSciTech, 2022)

Nano-strategies as Oral Drug Delivery Platforms for Treatment of Cancer: Challenges and Future Perspectives - Sheikh Shahnawaz Quadir; Vinod Saharan; Deepak Choudhary; Harish; C. P. Jain; Garima Joshi (AAPS PharmSciTech, 2022)

Venlafaxine HCl Encapsulated in Niosome: Green and Eco-friendly Formulation for the Management of Pain - Seyyed Mohammad Hassan Hashemi; Reza Enayatifard; Jafar Akbari; Majid Saeedi; Mohammad Seyedabadi; Katayoun Morteza-Semnani; Amirhossein Babaei; Kofi Asare-Addo; Ali Nokhodchi (AAPS PharmSciTech, 2022)

Enhancing Atorvastatin In Vivo Oral Bioavailability in the Presence of Inflammatory Bowel Disease and Irritable Bowel Syndrome Using Supercritical Fluid Technology Guided by wbPBPK Modeling in Rat and Human - Mo’tasem M. Alsmadi; Nour M. AL-Daoud; Rana M. Obaidat; Niazy A. Abu-Farsakh (AAPS PharmSciTech, 2022)

Preparation of 2-Methoxyestradiol Self-emulsified Drug Delivery System and the Effect on Combination Therapy with Doxorubicin Against MCF-7/ADM Cells - Chuan Yu; Chen Li; Haofeng Pan; Tian Li; Suna He (AAPS PharmSciTech, 2022)

Choline-Amino Acid-Derived Bio-ionic Liquids for Solubility Enhancement of Zafirlukast - Namrata Gaikwad; Swapna Kudal; Amelia M. Avachat (AAPS PharmSciTech, 2022)

Spray Pattern and Plume Geometry Testing and Methodology: An IPAC-RS Working Group Overview - Sherryl Baxter; Ben Myatt; Stephen Stein; Adrian Parkinson; Frank Chambers; Bill Doub; Jernej Grmas; Julie Suman; Keith Miller; Biswadip Sinha; Linda Liao; Ian Carter; et al. (AAPS PharmSciTech, 2022)

Effect of Different Molecular Weights of Chitosan on Formulation and Evaluation of Allopurinol-Loaded Nanoparticles for Kidney Targeting and in Management of Hyperuricemic Nephrolithiasis - Gurpreet Kandav; Dinesh Chandra Bhatt; Shailendra Kumar Singh (AAPS PharmSciTech, 2022)

Effect of Different Absorption Enhancers on the Nasal Absorption of Nalmefene Hydrochloride - Ting Zhang; Meng Li; Xiaolu Han; Guangjun Nie; Aiping Zheng (AAPS PharmSciTech, 2022)

Nanoemulsions Containing Megestrol Acetate: Development, Characterization, and Stability Evaluation - Tahir Emre Yalcin; Emre Tuncel; Cigdem Yucel; Figen Tirnaksiz (AAPS PharmSciTech, 2022)

Stiripentol Enteric Solid Dispersion-Loaded Effervescent Tablets: Enhanced Dissolution, Stability, and Absorption - Ying Wang; Siyuan Xu; Ziyue Xiao; Yuxin Jiang; Qi Jiang; Jun Li; Wei He (AAPS PharmSciTech, 2022)

Preparation and Spectroscopic Characterization of Inclusion Complexes of 3D Ball-Milled Rifampicin with β-cyclodextrin and γ-cyclodextrin - Yutaka Inoue; Mari Shigematsu; Takanori Komatsu; Toshio Oguchi; Florencio Jr Arce; Gerard Lee See (AAPS PharmSciTech, 2022)

The Molecular Mechanism of Propylene Glycol Monocaprylate on Skin Retention: Probing the Dual Roles on the Molecular Mobility and Collagen Connection in Roflumilast Cream - Yuxue Liu; Chao Liu; Wenxuan Jia; Wenwen Xu; Peng Quan; Liang Fang (AAPS PharmSciTech, 2022)

Transformation of Ritonavir Nanocrystal Suspensions into a Redispersible Drug Product via Vacuum Drum Drying - Barbara V. Schönfeld; Ulrich Westedt; Benjamin-Luca Keller; Karl G. Wagner (AAPS PharmSciTech, 2022)
The present study explored vacuum drum drying (VDD) as potential drying technique for the solidification of crystalline ritonavir nanosuspensions prepared by wet-ball milling. In detail, the impact of drying protectants (mannitol, lactose, trehalose) added to the ritonavir nanosuspension was assessed in dependence of the drum temperature with respect to processibility via VDD, resulting intermediate powder properties, remaining nanoparticulate redispersibility and crystallinity. A clear impact of the glass transition temperature ( T g ) of the drying protectant on the redispersibility/crystallinity of the VDD intermediate was observed. Increased T g of the drying protectant was associated with improved redispersibility/crystallinity at a defined drum temperature. Consequently, the high T g -substance trehalose and lactose showed a better performance than mannitol at higher drum temperatures. However, the processability and related powder properties were not in accordance with this observation. Mannitol containing formulations showed superior processibility to those containing trehalose/lactose. Moreover, the impact of the tableting and encapsulation process on the redispersibility of the VDD intermediate was studied for a selected formulation. Neither process demonstrated a negative impact on redispersibility. In conclusion, vacuum drum drying is a promising drying technique for the solidification of nanosuspensions to result in dried powder still containing ritonavir nanoparticles while demonstrating acceptable to good downstream processibility to tablets/capsules. Graphical Abstract

A Non-destructive Quantitative Transmission Raman Spectroscopy Method for Active Pharmaceutical Ingredient in Drug Product In-Use Samples Prepared in Dosing Vehicles - Gregory Doddridge; Edwin Hong; David Cheng Thiam Tan; Yemin Liu (AAPS PharmSciTech, 2022)

Co-crystallization of Amoxicillin Trihydrate and Potassium Clavulanate Provides a Promising Approach for Preparation of Sustained-Release Microspheres - Rana Obaidat; Batool Al-Ghzawi; Bashar Al-Taani; Nizar Al-Shar’i (AAPS PharmSciTech, 2022)

Sorafenib-Loaded PLGA-TPGS Nanosystems Enhance Hepatocellular Carcinoma Therapy Through Reversing P-Glycoprotein-Mediated Multidrug Resistance - Maomao Tang; Yuzhe Huang; Xiao Liang; Yaotian Tao; Ning He; Zhenbao Li; Jian Guo; Shuangying Gui (AAPS PharmSciTech, 2022)

Formulation and Evaluation of Topical Linezolid Nanoemulsion for Open Incision Wound in Diabetic Animal Model - Faheem Haider; Barkat Ali Khan; Muhammad Khalid Khan (AAPS PharmSciTech, 2022)

Spray-Dried Microspheres of Carboplatin: Technology to Develop Longer-Acting Injectable with Improved Physio-Chemical Stability, Toxicity, and Therapeutics - Shubham Thakur; Rasdeep Kour; Satwinderjeet Kaur; Subheet Kumar Jain (AAPS PharmSciTech, 2022)

Evaluation of Piperine as Natural Coformer for Eutectics Preparation of Drugs Used in the Treatment of Cardiovascular Diseases - Krissia Wilhelm-Romero; María Isabel Quirós-Fallas; José Roberto Vega-Baudrit; Teodolito Guillén-Girón; Felipe Vargas-Huertas; Mirtha Navarro-Hoyos; Andrea Mariela Araya-Sibaja (AAPS PharmSciTech, 2022)

Assessment of Resonant Acoustic Mixing for Low-Dose Pharmaceutical Powder Blends - Shashwat Gupta; Yu Elaine Pu; Minglu Li; Zhengmao Li; Juan G. Osorio (AAPS PharmSciTech, 2022)

Drotaverine Hydrochloride Superporous Hydrogel Hybrid System: a Gastroretentive Approach for Sustained Drug Delivery and Enhanced Viscoelasticity - Michael M. Farag; Mina M. Louis; Alia A. Badawy; Demiana I. Nessem; Nevine S. Abd Elmalak (AAPS PharmSciTech, 2022)
This study aims to prepare drotaverine hydrochloride superporous hydrogel hybrid systems (DSHH systems) to prolong its residence time in the stomach, provide extended release and reduce its frequency of administration. Drotaverine hydrochloride (DRH) is a spasmolytic drug that suffers from brief residence due to intestinal hypermotility during diarrheal episodes associated with gastrointestinal colics resulting in low bioavailability and repeated dosing. Eight DSHH systems were prepared using gas blowing technique. The prepared DSHH systems were evaluated regarding their morphology, incorporation efficiency, density, porosity, swelling ratio, viscoelastic property, erosion percentage and release kinetics. The FH8 formula containing equal proportion of chitosan (3%) /polyvinyl alcohol (3%) as strengthener and crosslinked with tripolyphosphate showed the highest incorporation efficiency (91.83 ± 1.33%), good swelling ratio (28.32 ± 3.15% after 24 h), optimum viscoelastic properties (60.19 ± 3.82 kPa) and sustained release profile (88.03 ± 2.15% after 24 h). A bioequivalence study was done to compare the bioavailability of the candidate formula versus Spasmocure®. Statistical analysis showed significant ( P Graphical abstract

Fluocinolone Acetonide Microemulsion in Combination with a Fractional Laser for the Treatment of Scalp Psoriasis - Voraphol Vejjabhinanta; Walaisiri Muangsiri; Pornpen Werawatganone (AAPS PharmSciTech, 2022)