In Vitro Testing of Sunscreens for Dermal Absorption: Method Comparison and Rank Order Correlation with In Vivo Absorption - Yang Yang; Ann-Marie Ako-Adounvo; Jiang Wang; Sergio G. Coelho; Steven A. Adah; Murali K. Matta; David Strauss; Theresa M. Michele; Jian Wang; Patrick J. Faustino; Thomas O’Connor; Muhammad Ashraf (AAPS PharmSciTech, 2022)

An Integrative QbD Approach for the Development and Optimization of Controlled Release Compressed Coated Formulation of Water-Soluble Drugs - Viral Shah; Ekta Khambhla; Manish Nivsarkar; Riddhi Trivedi; Rakesh K. Patel (AAPS PharmSciTech, 2022)

A New Approach for Characterizing the Thixotropic Properties of Gel Formulations as Sprayable Agents Based on Rheological Analysis - Takayuki Terukina; Yoshiki Uchiyama; Fumiya Kikuma; Saki Fukumitsu; Nana Iwata; Takanori Kanazawa; Hiromu Kondo (AAPS PharmSciTech, 2022)

Impact of Amylose-Amylopectin Ratio of Starches on the Mechanical Strength and Stability of Acetylsalicylic Acid Tablets - Natalia Veronica; Celine Valeria Liew; Paul Wan Sia Heng (AAPS PharmSciTech, 2022)
The two main components of starch — amylose and amylopectin, are responsible for its interaction with moisture. This study investigated how moisture sorption properties of the starches with different amylose-amylopectin ratio impacted tablet properties including drug stability. The starch samples were equilibrated to 33, 53, and 75% relative humidity (RH) and then assessed for tabletability, compactibility, and yield pressure. Effect of humidity on viscoelastic recovery was also evaluated. Tabletability and compactibility of high-amylose starch were better than that of high-amylopectin starch at 33 and 53% RH. However, at 75% RH, the reverse was observed. In terms of yield pressure, high-amylose starch had lower yield pressure than high-amylopectin starch. High-amylose starch tablets also exhibited lower extent of viscoelastic recovery than high-amylopectin starch tablets. The variations in the tableting properties were found to be related to relative locality of the sorbed moisture. Degradation of acetylsalicylic acid in high-amylose starch tablets at 75% RH, 40°C was less than the tablets with high-amylopectin starch. This observation could be attributed to the greater amount of water molecules binding sites in high-amylose starch. Furthermore, most of the sorbed moisture of high-amylose starch was internally absorbed moisture, therefore limiting the availability of diffusible sorbed moisture for degradation reaction. Findings from this study could provide better insights on the influence of amylose-amylopectin ratio on tableting properties and stability of moisture-sensitive drugs. This is of particular importance as starch is a common excipient in solid dosage forms.

Investigation of Quantitative X-ray Microscopy for Assessment of API and Excipient Microstructure Evolution in Solid Dosage Processing - Aiden Zhu; Chen Mao; Paul E. Luner; Joshua Lomeo; Chi So; Stephanie Marchal; Shawn Zhang (AAPS PharmSciTech, 2022)

Formulation Development and Pharmaceutical Evaluation of Lysiphyllum strychnifolium Topical Patches for Their Anti-inflammatory Potential - Yupaporn Sampaopan; Jirapornchai Suksaeree (AAPS PharmSciTech, 2022)

Curcumin and Derivatives in Nanoformulations with Therapeutic Potential on Colorectal Cancer - Sourour Idoudi; Takwa Bedhiafi; Yousef Mohammad Hijji; Nashiru Billa (AAPS PharmSciTech, 2022)
There is growing concern in the rise of colorectal cancer (CRC) cases globally, and with this rise is the presentation of drug resistance. Like other cancers, current treatment options are either invasive or manifest severe side effects. Thus, there is a move towards implementing safer treatment options. Curcumin (CUR), extracted from Curcuma longa , has received significant attention by scientists as possible alternative to chemotherapeutic agents. It is safe and effective against CRC and nontoxic in moderate concentrations. Crucially, it specifically modulates apoptotic effects on CRC. However, the use of CUR is limited by its low solubility and poor bioavailability in aqueous media. These limitations are surmountable through novel approaches, such as nanoencapsulation of CUR, which masks the physicochemical properties of CUR, thus potentiating its anti-CRC effects. Furthermore, chemical derivatization of CUR is another approach that can be used to address the above constraints. This review spans published work in the last two decades, with key findings employing either of the two approaches, in addition to a combined approach in managing CRC. The combined approach affords the possibility of better treatment outcomes but not widely investigated nor yet clinically implemented. Graphical Abstract

Characterizing the Effects of Nasal Prong Interfaces on Aerosol Deposition in a Preterm Infant Nasal Model - Karl Bass; Mohammad A. M. Momin; Connor Howe; Ghali Aladwani; Sarah Strickler; Arun V. Kolanjiyil; Michael Hindle; Robert M. DiBlasi; Worth Longest (AAPS PharmSciTech, 2022)
The objective of this study was to characterize the effects of multiple nasal prong interface configurations on nasal depositional loss of pharmaceutical aerosols in a preterm infant nose-throat (NT) airway model. Benchmark in vitro experiments were performed in which a spray-dried powder formulation was delivered to a new preterm NT model with a positive-pressure infant air-jet dry powder inhaler using single- and dual-prong interfaces. These results were used to develop and validate a computational fluid dynamics (CFD) model of aerosol transport and deposition in the NT geometry. The validated CFD model was then used to explore the NT depositional characteristic of multiple prong types and configurations. The CFD model highlighted a turbulent jet effect emanating from the prong(s). Analysis of NT aerosol deposition efficiency curves for a characteristic particle size and delivery flowrate (3 µm and 1.4 L/min (LPM)) revealed little difference in NT aerosol deposition fraction (DF) across the prong insertion depths of 2–5 mm (DF = 16–24%) with the exception of a single prong with 5-mm insertion (DF = 36%). Dual prongs provided a modest reduction in deposition vs. a single aerosol delivery prong at the same flow for insertion depths Graphical Abstract

Design and Evaluation of Two-Step Biorelevant Dissolution Methods for Docetaxel Oral Formulations - Brijesh Shah; Xiaowei Dong (AAPS PharmSciTech, 2022)

Construction and Biological Evaluation of Multiple Modification Hollow Mesoporous Silicone Doxorubicin Nanodrug Delivery System - Mengru Hu; Wenjing Zhang; Weidong Chen; Yunna Chen; Qianqian Huang; Qianqian Bao; Tongyuan Lin; Lei Wang; Shantang Zhang (AAPS PharmSciTech, 2022)

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)

Convective Solvent Transport Pathways for Absorption of Drugs from Topical Formulation - Abhijeet Maurya; Jungeun Bae; Vanaja Kenchappa; H. N. Shivakumar; Howard Maibach; Michael A. Repka; S. Narasimha Murthy (AAPS PharmSciTech, 2022)

Improvement in Bioavailability and Pharmacokinetic Characteristics of Efavirenz with Booster Dose of Ritonavir in PEGylated PAMAM G4 Dendrimers - Rohini Kharwade; Sachin More; Elizabeth Suresh; Amol Warokar; Nilesh Mahajan; Ujwala Mahajan (AAPS PharmSciTech, 2022)

ASD Formation Prior to Material Characterization as Key Parameter for Accurate Measurements and Subsequent Process Simulation for Hot-Melt Extrusion - Kevin Kayser; Marius Monschke; Karl G. Wagner (AAPS PharmSciTech, 2022)
Process simulation facilitates scale-up of hot-melt extrusion (HME) and enhances proper understanding of the underlying critical process parameters. However, performing numeric simulations requires profound knowledge of the employed materials’ properties. For example, an accurate description of the compounds’ melt rheology is paramount for proper simulations. Hence, sample preparation needs to be optimized to yield results as predictive as possible. To identify the optimal preparation method for small amplitude oscillatory shear (SAOS) rheological measurements, binary mixtures of hydroxypropylmethylcellulose acetate succinate or methacrylic acid ethyl acrylate copolymer (Eudragit L100-55) together with the model drugs celecoxib and ketoconazole were prepared. The physical powder mixtures were introduced into the SAOS as a compressed tablet or a disk prepared via vacuum compression molding (VCM). Simulations with the derived parameters were conducted and compared to lab-scale extrusion trials. VCM was identified as the ideal preparation method resulting in the highest similarity between simulated and experimental values, while simulation based on conventional powder-based methods insufficiently described the HME process.

Luliconazole Nail Lacquer for the Treatment of Onychomycosis: Formulation, Characterization and In Vitro and Ex Vivo Evaluation - Deepa Dehari; Abhishesh Kumar Mehata; Vishnu Priya; Dharmnath Parbat; Deepak Kumar; Anand Kumar Srivastava; Sanjay Singh; Ashish Kumar Agrawal (AAPS PharmSciTech, 2022)

Implementation of Dynamic and Static Moisture Control in Fluidized Bed Granulation - Liang Zhong; Lele Gao; Lian Li; Lei Nie; Hui Zhang; Zhongyu Sun; Ruiqi Huang; Zhaobang Zhou; Wenping Yin; Hui Wang; Hengchang Zang (AAPS PharmSciTech, 2022)

Development of a Microgram Scale Video-Microscopic Method to Investigate Dissolution Behavior of Poorly Water-Soluble Drugs - Malte Bøgh Senniksen; Juliane Fjelrad Christfort; Riccardo Marabini; Erik Spillum; Wayne Matthews; Luigi Da Vià; Jakob Plum; Thomas Rades; Anette Müllertz (AAPS PharmSciTech, 2022)

Penetration Enhancement Strategies for Intradermal Delivery of Cromolyn Sodium - Miranda Holman; Akeemat Tijani; Jeffrey Klein; Dorcas Frempong; Steven Dinh; Ashana Puri (AAPS PharmSciTech, 2022)

Effects of Autoclaving and Freeze-Drying on Physicochemical Properties of Plectranthus esculentus Starch Derivatives - Ruth E. Guktur; Elijah I. Nep; Chinwe U. Kemas; Patrick O. Olorunfemi; Ndidi C. Ngwuluka; Nelson A. Ochekpe; Atiene S. Sagay (AAPS PharmSciTech, 2022)

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage - Tatianny de Araújo Andrade; Luana Heimfarth; Danillo Menezes dos Santos; Márcio Roberto Viana dos Santos; Ricardo Luiz Cavalcanti de Albuquerque-Júnior; Agenor Gomes dos Santos-Neto; Guilherme Rodolfo Souza de Araujo; Ana Amélia Moreira Lira; Saulo Santos Matos; Luiza Abrahão Frank; Thallita Kelly Rabelo; Lucindo José Quintans-Júnior; et al. (AAPS PharmSciTech, 2022)

Prediction and Construction of Drug-Polymer Binary System Thermodynamic Phase Diagram in Amorphous Solid Dispersions (ASDs) - Zhiqing Hu; Pengchong Xu; Eman A. Ashour; Michael A. Repka (AAPS PharmSciTech, 2022)

Pickering Dry Emulsion System for Improved Oral Delivery of Fenofibrate - Nitin V. Jadhav; Manoj A. Pawar; Pradeep R. Vavia (AAPS PharmSciTech, 2022)

A Hypoxia-Sensitive Drug Delivery System Constructed by Nitroimidazole and its Application in the Treatment of Hepatocellular Carcinoma - Tingting Meng; Yinghong Li; Ying Tian; Mingxing Ma; Kequan Shi; Xuwei Shang; Hong Yuan; Fuqiang Hu (AAPS PharmSciTech, 2022)

Retraction Note: Bimatoprost-Loaded Silica Shell–Coated Nanoparticles-Laden Soft Contact Lenses to Manage Glaucoma: In Vitro and In Vivo Studies - He Xiaojie; Jiang Fagang; Jing Jun; Wang Chunfang; Li Chengquan; Wang Xinghua (AAPS PharmSciTech, 2022)

Current Status and Challenges of Analytical Methods for Evaluation of Size and Surface Modification of Nanoparticle-Based Drug Formulations - Yuki Takechi-Haraya; Takashi Ohgita; Yosuke Demizu; Hiroyuki Saito; Ken-ichi Izutsu; Kumiko Sakai-Kato (AAPS PharmSciTech, 2022)

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)
The importance of lipid-based formulations in addressing solubility and ultimately the bioavailability issues of the emerging drug entities is undeniable. Yet, there is scarcity of literature on lipid excipient chemistry and performance, notably in relation to oxidative stability. While not all lipid excipients are prone to oxidation, those with sensitive moieties offer drug delivery solutions that outweigh the manageable oxidative challenges they may present. For example, caprylocaproyl polyoxylglycerides help solubilize and deliver cancer drug to patients, lauroyl polyoxylglycerides enhance the delivery of cholesterol lowering drug, and sesame/soybean oils are critical part of parenteral nutrition. Ironically, excipients with far greater oxidative propensity are omnipresent in pharmaceutical products, a testament to the manageability of oxidative challenges in drug development. Successful formulation development requires awareness of what, where, and how formulation stability may be impacted, and accordingly taking appropriate steps to circumvent or meet the challenges ahead. Aiming to fill the information gap from a drug delivery scientist perspective, this review discusses oxidation pathways, prooxidants, antioxidants, and their complex interplay, which can paradoxically take opposite directions depending on the drug delivery system.

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

3D Bioprinting of Human Hollow Organs - Nabanita Panja; Sumana Maji; Sabyasachi Choudhuri; Kazi Asraf Ali; Chowdhury Mobaswar Hossain (AAPS PharmSciTech, 2022)

Optimization of DOTAP/chol Cationic Lipid Nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery - Mengwei Sun; Utkarsh J. Dang; Yuhao Yuan; Alexandra Maria Psaras; Ositomiwa Osipitan; Tracy A. Brooks; Fake Lu; Anthony J. Di Pasqua (AAPS PharmSciTech, 2022)

Self-Emulsifying Systems for Delivery of Bioactive Compounds from Natural Origin - Mariana Carla de Oliveira; Marcos Luciano Bruschi (AAPS PharmSciTech, 2022)

Pharmacotechnical Evaluation by SeDeM Expert System to Develop Orodispersible Tablets - Monica R. P. Rao; Sharwari Sapate; Ashwini Sonawane (AAPS PharmSciTech, 2022)

Albumin-Embellished Arsenic Trioxide-Loaded Polymeric Nanoparticles Enhance Tumor Accumulation and Anticancer Efficacy via Transcytosis for Hepatocellular Carcinoma Therapy - Yu Huang; Zhishi Xu; Yinghui Wei; Shunping Han; Xinjun Cai; Danfei Chen (AAPS PharmSciTech, 2022)

Spanlastics a Novel Nanovesicular Carrier: Its Potential Application and Emerging Trends in Therapeutic Delivery - Mohd Danish Ansari; Zoya Saifi; Jayamanti Pandit; Iram Khan; Pavitra Solanki; Yasmin Sultana; Mohd Aqil (AAPS PharmSciTech, 2022)

Development and Optimization of Vitamin D3 Solid Self-Microemulsifying Drug Delivery System: Investigation of Flowability and Shelf Life - Pankaj V. Dangre; Navya J. Gurram; Sanjay J. Surana; Shailesh S. Chalikwar (AAPS PharmSciTech, 2022)

Polysialic Acid Self-assembled Nanocomplexes for Neutrophil-Based Immunotherapy to Suppress Lung Metastasis of Breast Cancer - Chuizhong Fan; Cong Li; Shuang Lu; Xiaoxue Lai; Shuo Wang; Xinrong Liu; Yanzhi Song; Yihui Deng (AAPS PharmSciTech, 2022)

Physiologically Based Biopharmaceutics Model of Vildagliptin Modified Release (MR) Tablets to Predict In Vivo Performance and Establish Clinically Relevant Dissolution Specifications - Muzaffaruddin Ahmed Madny; Pandurang Deshpande; Venkat Tumuluri; Parag Borde; Ramachandra Sangana (AAPS PharmSciTech, 2022)

Design, Characterization, and Evaluation of Diosmetin-Loaded Solid Self-microemulsifying Drug Delivery System Prepared by Electrospray for Improved Bioavailability - Zhengqing Gu; Yuanyuan Xue; Shuang Li; Michael Adu-Frimpong; Ying Xu; Jiangnan Yu; Ximing Xu; Yuan Zhu (AAPS PharmSciTech, 2022)

Rethinking Breast Cancer Chemoprevention: Technological Advantages and Enhanced Performance of a Nanoethosomal-Based Hydrogel for Topical Administration of Fenretinide - Alexsandra Conceição Apolinário; Giovanna Cassone Salata; Marcelo Medina de Souza; Marlus Chorilli; Luciana Biagini Lopes (AAPS PharmSciTech, 2022)

Innovative, Sugar-Free Oral Hydrogel as a Co-administrative Vehicle for Pediatrics: a Strategy to Enhance Patient Compliance - Margarida Pereira; Filipa Cosme Silva; Sandra Simões; Helena Margarida Ribeiro; António José Almeida; Joana Marto (AAPS PharmSciTech, 2022)

Research Progress of Preparation Technology of Ion-Exchange Resin Complexes - Tian-Yi Zhang; Ruo-Fei Du; You-Jie Wang; Jia-Liang Hu; Fei Wu; Yi Feng (AAPS PharmSciTech, 2022)

In Vitro Evaluation of a Foamable Microemulsion Towards an Improved Topical Delivery of Diclofenac Sodium - Braa Hajjar; Jieyu Zuo; Chulhun Park; Shirzad Azarmi; Daniela Amaral Silva; Nádia Araci Bou-Chacra; Raimar Löbenberg (AAPS PharmSciTech, 2022)

Development, Characterization, and Investigation of In Vivo Targeted Delivery Efficacy of Luteolin-Loaded, Eudragit S100-Coated mPEG-PLGA Nanoparticles - Xia Liu; Mengying Zhang; Yuxin Tian; Ruijia Liu; Yunfei Wang; Feifei Guo; Yanling Gong; Meixing Yan (AAPS PharmSciTech, 2022)

Ketoprofen–FA Co-crystal: In Vitro and In Vivo Investigation for the Solubility Enhancement of Drug by Design of Expert - Sunita Devi; Ashwani Kumar; Archana Kapoor; Vikas Verma; Snehlata Yadav; Meenakshi Bhatia (AAPS PharmSciTech, 2022)

Correction to: Fabrication, Evaluation, In Vivo Pharmacokinetic and Toxicological Analysis of pH-Sensitive Eudragit S-100-Coated Hydrogel Beads: a Promising Strategy for Colon Targeting - Sadia Rehman; Nazar Muhammad Ranjha; Hina Shoukat; Asadullah Madni; Faiz Ahmad; M. Rafi Raza; Qazi Adnan Jameel; Abdul Majeed; Nasreen Ramzan (AAPS PharmSciTech, 2022)

A Comprehensive Investigation Regarding the Differentiation of the Procurable COVID-19 Vaccines - Surojit Banerjee; Debadri Banerjee; Anupama Singh; Vikas Anand Saharan (AAPS PharmSciTech, 2022)

PEGylated Lecithin-Chitosan Nanoparticle–Encapsulated Alphα-Terpineol for In Vitro Anticancer Effects - Bahar Zarei; Masoud Homayouni Tabrizi; Amir Rahmati (AAPS PharmSciTech, 2022)

The Physical Stability of Felodipine and Its Recrystallization from an Amorphous Solid Dispersion Studied by NMR Relaxometry - A. Pajzderska; J. Mielcarek; J. Wąsicki (AAPS PharmSciTech, 2022)

A Fundamental Study on Compression Properties and Strain Rate Sensitivity of Spray-Dried Amorphous Solid Dispersions - S. Doktorovová; E. H. Stone; J. Henriques (AAPS PharmSciTech, 2022)

3D Printing: Applications in Tissue Engineering, Medical Devices, and Drug Delivery - BG Pavan Kalyan; Lalit Kumar (AAPS PharmSciTech, 2022)
The gemstone of 3-dimensional (3D) printing shines up from the pyramid of additive manufacturing. Three-dimensional bioprinting technology has been predicted to be a game-changing breakthrough in the pharmaceutical industry since the last decade. It is fast evolving and finds its seats in a variety of domains, including aviation, defense, automobiles, replacement components, architecture, movies, musical instruments, forensic, dentistry, audiology, prosthetics, surgery, food, and fashion industry. In recent years, this miraculous manufacturing technology has become increasingly relevant for pharmaceutical purposes. Computer-aided drug (CAD) model will be developed by computer software and fed into bioprinters. Based on material inputs, the printers will recognize and produce the model scaffold. Techniques including stereolithography, selective laser sintering, selective laser melting, material extrusion, material jetting, inkjet-based, fused deposition modelling, binder deposition, and bioprinting expedite the printing process. Distinct advantages are rapid prototyping, flexible design, print on demand, light and strong parts, fast and cost-effective, and environment friendly. The present review gives a brief description of the conceptional 3-dimensional printing, followed by various techniques involved. A short note was explained about the fabricating materials in the pharmaceutical sector. The beam of light is thrown on the various applications in the pharma and medical arena.

Pharmaceutical Process Modeling - Alexander Russell; Maxx Capece (AAPS PharmSciTech, 2022)

Anti-oxidant Containing Nanostructured Lipid Carriers of Ritonavir: Development, Optimization, and In Vitro and In Vivo Evaluations - Srinivas Reddy Jitta; Navya Ajitkumar Bhaskaran; Salwa; Lalit Kumar (AAPS PharmSciTech, 2022)
Acquired immunodeficiency syndrome (AIDS) is a condition caused by the infection of a retrovirus namely, human immunodeficiency virus (HIV). Currently, highly active anti-retroviral therapy (HAART), a combination of anti-viral drugs belonging to different classes is considered to be effective in the management of HIV. Ritonavir, a protease inhibitor (PI), is one of the most important components of the HAART regimen. Because of its lower bioavailability and severe side effects, presently, ritonavir is not being used as a PI. However, this drug is being used as a pharmacokinetic boosting agent for other PIs such as lopinavir and in lower doses. The current study aimed to develop nanostructured lipid carriers (NLCs) encapsulating ritonavir to reduce its side effects and enhance oral bioavailability. Ritonavir-loaded NLCs were developed using a combination of two different solid lipids and liquid lipids. Alpha-tocopherol, a well-known anti-oxidant, was used as an excipient (liquid lipid) in the development of NLCs which were prepared using a simple hot-emulsion and ultrasonication method. Drug-excipient studies were performed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). QbD approach was followed for the screening and optimization of different variables. The developed NLCs were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). Furthermore, NLCs were studied for their in vitro drug release profile, and finally, pharmacokinetic parameters were determined using in vivo pharmacokinetic studies. The optimized NLC size was in the range of 273.9 to 458.7 nm, PDI of 0.314 to 0.480, ZP of −52.2 to − 40.9 mV, and EE in the range of 47.37 to 74.51%. From in vitro drug release, it was found that the release of drug in acidic medium was higher than phosphate buffer pH 6.8. Finally, in vivo pharmacokinetic studies revealed a 7-fold enhancement in the area under the curve (AUC) and more than 10-fold higher C max with the optimized formulation in comparison to pure drug suspension.

Multifunctional Role of Silica in Pharmaceutical Formulations - Yating Gao; Yue Zhang; Yanlong Hong; Fei Wu; Lan Shen; Youjie Wang; Xiao Lin (AAPS PharmSciTech, 2022)

Silymarin-Encapsulated Xanthan Gum–Stabilized Selenium Nanocarriers for Enhanced Activity Against Amyloid Fibril Cytotoxicity - Vanshul Saini; Ajit Singh; Rahul Shukla; Keerti Jain; A. K. Yadav (AAPS PharmSciTech, 2022)

Design and Development of Solid SMEDDS and Liquisolid Formulations of Lovastatin, for Improved Drug Dissolution and In vivo Effects—a Pharmacokinetic and Pharmacodynamic Assessment - Dinesh Suram; Kishan Veerabrahma (AAPS PharmSciTech, 2022)

Microneedle-Based Vaccine Delivery: Review of an Emerging Technology - Ihab Mansoor; Heba A. Eassa; Kamilia H. A. Mohammed; Marwa A. Abd El-Fattah; Marwa H. Abdo; Eman Rashad; Hadeer A. Eassa; Asmaa Saleh; Omnya M. Amin; Mohamed Ismail Nounou; Ola Ghoneim (AAPS PharmSciTech, 2022)

Monolaurin-Loaded Gel-Like Microemulsion for Oropharyngeal Candidiasis Treatment: Structural Characterisation and In Vitro Antifungal Property - Sukannika Tubtimsri; Yotsanan Weerapol; Siriwat Soontaranon; Chutima Limmatvapirat; Sontaya Limmatvapirat (AAPS PharmSciTech, 2022)

Simulation Models for Prediction of Bioavailability of Medicinal Drugs—the Interface Between Experiment and Computation - Mahmoud E. Soliman; Adeniyi T. Adewumi; Oluwole B. Akawa; Temitayo I. Subair; Felix O. Okunlola; Oluwayimika E. Akinsuku; Shahzeb Khan (AAPS PharmSciTech, 2022)

Enhanced Intramuscular Bioavailability of Cannabidiol Using Nanocrystals: Formulation, In Vitro Appraisal, and Pharmacokinetics - Xinzhen Fu; Shiji Xu; Zhi Li; Kun Chen; Huaying Fan; Yu Wang; Zeping Xie; Lijuan Kou; Shumin Zhang (AAPS PharmSciTech, 2022)

Transdermal Delivery of Baclofen Using Iontophoresis and Microneedles - Mohammad Shajid Ashraf Junaid; Ajay K. Banga (AAPS PharmSciTech, 2022)

One-Way Intestinal Perfusion of PVP/VA–Poloxamer 188–Curcuma longa L. Extract Solid Dispersion in Rats In Vivo and Its Effect on HSC–T6 Cell Proliferation - Jie Gao; Yi Shi; Yunfeng Han; Xi Tang; Ruohong Bi; Lin Pan; Xianrong Lai (AAPS PharmSciTech, 2022)

Release of Ropinirole in Acrylate Transdermal Patches: Mutual Interactions Between Formulation Variables - Paterna-Paterna Jesús; Miñarro-Carmona Montserrat; Pujol-Dilme Mª Dolors; Ticó-Grau Josep Ramon; Boix-Montañés Antonio (AAPS PharmSciTech, 2022)
The aim of this study is to evaluate the cooperative interactions between formulation variables of ropinirole transdermal patches and characterize the effects of drug loading and crystallinity, degree of ionization and drug-polymer solubilization, functionalization of acrylate polymeric basis, and the addition of permeation enhancers over the release profiles. Several series of transdermal films based on carboxylic or hydroxylic acrylates (DuroTak®) and containing 1 to 10% ropinirole hydrochloride were laminated by mold-casting and evaporation. Formulations were characterized for crystallinity, drug particle size, drug assay, and residual solvents. Release profiles were obtained at different drug ionization state using paddle over disk apparatus. Mechanisms were elucidated with nonlinear data fitting of relevant release equations. Fickian and erosion processes were evaluated with the Peppas–Sahlin equation, and burst release risks were estimated as an independent term added to Higuchi kinetics. X-ray diffraction and microscopy evidenced differences in drug-polymer solubilization and density of drug crystals. Concerning drug release, area under the curve of dissolved quantities and release percentage were discriminant variables in mutual influence. Peppas–Shalin equation was the majority descriptor of release suggesting a combination of Fickian and erosion processes, revealing a decrease in the Fickian component as drug loading increased. Major burst release risks were evidenced mostly with Higuchi kinetics with vinylacetate acrylates. The carboxylic polymer without vinylacetate provided the best release extent, being more highly efficient as lower the drug loading was. Permeation enhancers with carboxylic or aliphatic radicals have, additionally, modified the release properties of ropinirole. Chemical interactions between the drug and acrylic polymers have been demonstrated. Only the effect with carboxylic polymer is pH dependent. The vinyl acetate comonomer reduces the drug release rate most effectively in formulations with low drug loads. The acrylic polymers without vinylacetate achieved the highest drug solubilization and thus the highest degree of release, providing a release of approximately 15% of the drug load.

Atorvastatin Entrapped Noisome (Atrosome): Green Preparation Approach for Wound Healing - Shidrokh Abootorabi; Jafar Akbari; Majid Saeedi; Mohammad Seyedabadi; Mohammad Ranaee; Kofi Asare-Addo; Ali Nokhodchi (AAPS PharmSciTech, 2022)
The present study aimed to formulate atorvastatin niosome (Atrosome) through an ultrasonic technique and to determine its contribution to the extent of wound healing in an animal model. The optimized Atrosome formulation (Atrosome-2) was stable at 4 °C for 3 months. Differential scanning calorimetry (DSC), ATR-Fourier transform infrared spectroscopy (ATR-FTIR), and powder X-ray diffraction (PXRD) analysis revealed that atorvastatin (ATR) was well encapsulated within the niosomes either in a stabilized amorphous form or a molecularly dispersed state. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscope (AFM) confirmed the spherical nature of the Atrosomes. The optimized formulation showed polydispersity index, particle size, drug encapsulation efficiency (EE%), and zeta potential of 0.457 ± 0.05, 196.33 ± 6.45 nm, 86.15 ± 0.58 %, and − 20.73 ± 0.98 mV, respectively. ATR release from the Atrosome gel followed the first-order kinetic model and showed no cytotoxicity in the in vitro cytotoxicity test. Cell viability (human foreskin fibroblast cell line) was nearly 99%. An excision wound model was also applied in male Wistar rats to examine the in vivo efficacy of the optimized formulation, followed by investigating malondialdehyde (MDA, an end-product of lipid peroxidation), superoxide dismutase (SOD, an endogenous antioxidant), hydroxyproline levels, and glutathione peroxidase (GPx) in skin tissue samples. MDA significantly decreased in the Atrosome gel group after 21 days, while GPx, SOD, and hydroxyproline levels demonstrated an increase. According to histological results, rats receiving Atrosomes were treated effectively faster when compared to the other formulation used.

Preparation and In Vitro and In Vivo Evaluation of a Testosterone Film Forming Gel for the Treatment of Hypoactive Sexual Desire Disorder in Women - Jia Zeng; Tan-Fang Xie; Ting Huang; Fang Li; Zhi-Ping Wang; Ling-Lin Feng (AAPS PharmSciTech, 2022)

Nanosized-Loratadine Embedded Orodispersible Films for Enhanced Bioavailability: Scalable Preparations and Characterizations - Khanh Van Nguyen; Huyen Thi Nguyen; Lien Ha Thi Nghiem; Mao Van Can; Tuan Hiep Tran (AAPS PharmSciTech, 2022)

Mupirocin-Loaded Chitosan Microspheres Embedded in Piper betle Extract Containing Collagen Scaffold Accelerate Wound Healing Activity - Mansi Budhiraja; Sobiya Zafar; Sohail Akhter; Majed Alrobaian; Md Abdur Rashid; Md. Abul Barkat; Sarwar Beg; Farhan J. Ahmad (AAPS PharmSciTech, 2022)

A Nanocrystal Platform Based on Metal-Phenolic Network Wrapping for Drug Solubilization - Feifei Huang; Xiaohong Jiang; Marwa A. Sallam; Xingwang Zhang; Wei He (AAPS PharmSciTech, 2022)

Calcium Ion-Sodium Alginate-Piperine-Based Microspheres: Evidence of Enhanced Encapsulation Efficiency, Bio-Adhesion, Controlled Delivery, and Oral Bioavailability of Isoniazid - Darshan R. Telange; Ravindra R. Pandharinath; Anil M. Pethe; Shirish P. Jain; Prashant L. Pingale (AAPS PharmSciTech, 2022)

Preparation and Evaluation of Novel Supersaturated Solid Dispersion of Magnolol - Jing Zhao; Pan Gao; Chengqiao Mu; Jingqi Ning; Wenbin Deng; Dongxu Ji; Haowei Sun; Xiangrong Zhang; Xinggang Yang (AAPS PharmSciTech, 2022)

In Vitro and In Vivo Evaluations of Berberine-Loaded Microparticles Filled In-House 3D Printed Hollow Capsular Device for Improved Oral Bioavailability - Dinesh Choudhury; Aishwarya Jala; Upadhyayula Suryanarayana Murty; Roshan M. Borkar; Subham Banerjee (AAPS PharmSciTech, 2022)

An Insight into Eudragit S100 Preserving Mechanism of Cinnarizine Supersaturation - Maryam Maghsoodi; Saeideh Mollaie Astemal; Ali Nokhodchi; Hossein Kiaie; Ali Baradar Khoshfetrat; Fatemeh Talebi (AAPS PharmSciTech, 2022)

Mesoporous Silica Carrier-Based Composites for Taste-Masking of Bitter Drug: Fabrication and Palatability Evaluation - Weifeng Zhang; Guoxiang Li; Chaoqiang Xiao; Xin Chang; Ying Sun; Weiping Fan; Bing Tian; Di Gao; Yao Xiao; Xueping Wu; Shuwang He; Guangxi Zhai (AAPS PharmSciTech, 2022)

Microwave-Assisted Physically Cross-Linked Chitosan-Sodium Alginate Hydrogel Membrane Doped with Curcumin as a Novel Wound Healing Platform - Hassan A. Albarqi; Abdulsalam A. Alqahtani; Irfan Ullah; Nauman Rahim Khan; Hafiz Muhammad Basit; Tayyaba Iftikhar; Abdul Wahab; Muhammad Ali; Muhammad Badar (AAPS PharmSciTech, 2022)

Formulation of Apigenin-Cyclodextrin-Chitosan Ternary Complex: Physicochemical Characterization, In Vitro and In Vivo Studies - Mohammed Jafar; Mohammed Saifuddin Khalid; Hajer Alghamdi; Mohd Amir; Sarah Aon Al Makki; Ohud Saud Alotaibi; Afnan Ali Al Rmais; Syed Sarim Imam; Sultan Alshehri; Sadaf Jamal Gilani (AAPS PharmSciTech, 2022)

In Vitro Assessment of Sunscreen Efficacy Using Fourier Transform Infrared (FTIR) Spectroscopy on Synthetic Skin - Farah Mahdi Abd Ali Al-Saeedi; Eman Zmaily Dahmash (AAPS PharmSciTech, 2022)

Donepezil HCl Liposomes: Development, Characterization, Cytotoxicity, and Pharmacokinetic Study - Amarjitsing Rajput; Shital Butani (AAPS PharmSciTech, 2022)

Transfersome Hydrogel Containing 5-Fluorouracil and Etodolac Combination for Synergistic Oral Cancer Treatment - Srivarsha Reddy Bollareddy; Vandana Krishna; Girdhari Roy; Deepika Dasari; Arti Dhar; Venkata Vamsi Krishna Venuganti (AAPS PharmSciTech, 2022)

Investigation of Chloroquine Resinate Feasibility and In Vitro Taste Masking Evaluation for Pediatric Formulations - Thiago F. Guimarães; Italo Carlos F. Vital; Eduardo G. R. de Sousa; Janine Boniatti; Thiago B. Bandini; Olívia Carr; Osvaldo N. Oliveira; Flávio M. Shimizu; Laís B. da Fonseca; Alessandra L. Viçosa (AAPS PharmSciTech, 2022)

Improving Water-Absorption and Mechanical Strength: Lyotropic Liquid Crystalline–Based Spray Dressings as a Candidate Wound Management System - Chen Wang; Jingtian Chen; Xiao Yue; Xiao Xia; Ziqiang Zhou; Guanlin Wang; Xuejuan Zhang; Ping Hu; Ying Huang; Xin Pan; Chuanbin Wu (AAPS PharmSciTech, 2022)

Direct Compaction Drug Product Process Modeling - Alexander Russell; John Strong; Sean Garner; William Ketterhagen; Michelle Long; Maxx Capece (AAPS PharmSciTech, 2022)
Most challenges during the development of solid dosage forms are related to the impact of any variations in raw material properties, batch size, or equipment scales on the product quality and the control of the manufacturing process. With the ever pertinent restrictions on time and resource availability versus heightened expectations to develop, optimize, and troubleshoot manufacturing processes, targeted and robust science-based process modeling platforms are essential. This review focuses on the modeling of unit operations and practices involved in batch manufacturing of solid dosage forms by direct compaction. An effort is made to highlight the key advances in the past five years, and to propose potentially beneficial future study directions.

Computational Modeling of Drying of Pharmaceutical Wet Granules in a Fluidized Bed Dryer Using Coupled CFD-DEM Approach - Hossain Aziz; Syed N. Ahsan; Giovanni De Simone; Yijie Gao; Bodhisattwa Chaudhuri (AAPS PharmSciTech, 2022)

The Optimized Formulation of Tamoxifen-Loaded Niosomes Efficiently Induced Apoptosis and Cell Cycle Arrest in Breast Cancer Cells - Iman Akbarzadeh; Mahsa Farid; Mehrnoosh Javidfar; Negar Zabet; Bahare Shokoohian; Mandana Kazem Arki; Anastasia Shpichka; Hassan Noorbazargan; Hamid Asadzadeh Aghdaei; Nikoo Hossein-khannazer; Peter Timashev; Pooyan Makvandi; et al. (AAPS PharmSciTech, 2022)

Creation of Hydrochlorothiazide Pharmaceutical Cocrystals Via Hot-Melt Extrusion for Enhanced Solubility and Permeability - Sagar Narala; Dinesh Nyavanandi; Abdullah Alzahrani; Suresh Bandari; Feng Zhang; Michael A. Repka (AAPS PharmSciTech, 2022)

Non-ionic Surfactants as a P-Glycoprotein(P-gp) Efflux Inhibitor for Optimal Drug Delivery—A Concise Outlook - Sachin Rathod; Heta Desai; Rahul Patil; Jayant Sarolia (AAPS PharmSciTech, 2022)

Comparison of HPMC Inhalation-Grade Capsules and Their Effect on Aerosol Performance Using Budesonide and Rifampicin DPI Formulations - Li Ding; Ashlee D. Brunaugh; Rishi Thakkar; Christian Lee; Qingyan Jenny Zhao; Justin Kalafat; Mohammed Maniruzzaman; Hugh D. C. Smyth (AAPS PharmSciTech, 2022)

Preparation and Evaluation of Polyvinylpyrrolidone Electrospun Nanofiber Patches of Pioglitazone for the Treatment of Atopic Dermatitis - Rana Obaidat; Ayat Abu Shameh; Mohannad Aljarrah; Rania Hamed (AAPS PharmSciTech, 2022)

Cyclodextrin/Adamantane-Grafted Polyethylene Glycol–Based Self-assembling Constructs for Topical Delivery of Ketorolac Tromethamine: Formulation, Characterization, and In Vivo Studies - Ahmed A. H. Abdellatif; Ahmed M. Mohammed; Gamal Zayed; Saleh Abd El-Rasoul; Saud Almawash; Mohamed A. Safwat; Shaaban K. Osman (AAPS PharmSciTech, 2022)

A Strategy for the Effective Optimization of Pharmaceutical Formulations Based on Parameter-Optimized Support Vector Machine Model - Siqi Wang; Jianping Yang; Hengwei Chen; Kexin Chu; Xuefei Yu; Yaqiong Wei; Haixia Zhang; Mengjie Rui; Chunlai Feng (AAPS PharmSciTech, 2022)

Preparation and Characterization of Furosemide Solid Dispersion with Enhanced Solubility and Bioavailability - Fangfang Zhang; Jingwei Mao; Guangyan Tian; Hulin Jiang; Qingri Jin (AAPS PharmSciTech, 2022)

Correction to: In Vivo and In Vitro Taste Assessment of Artesunate-Mefloquine, Praziquantel, and Benznidazole Drugs for Neglected Tropical Diseases and Pediatric Patients - Janine Boniatti; Marcelo R. R. Tappin; Rafaela G. da S Teixeira; Tamires de A V Gandos; Luis P. S. Rios; Izabelle A. M. Ferreira; Karina C. Oliveira; Sabrina Calil-Elias; Aila K. M. Santana; Laís B. da Fonseca; Flavio M. Shimizu; Olívia Carr; et al. (AAPS PharmSciTech, 2022)

Development and Validation of HPLC Method for Efinaconazole: Application to Human Nail Permeation Studies - Praveen Kolimi; Vijay Kumar Shankar; Abhishek Shettar; Srinath Rangappa; Michael A. Repka; S. Narasimha Murthy (AAPS PharmSciTech, 2022)

QbD Approach towards Robust Design Space for Flutamide/PiperineSelf-Emulsifying Drug Delivery System with Reduced Liver Injury - Mithun Saha; Pallabi Sikder; Aditi Saha; Sharha Shah; Sharmin Sultana; Tushar Emran; Ananna Banik; Zahidul Islam; Muhammad Saiful Islam; Shazid Md. Sharker; Hasan Mahmud Reza (AAPS PharmSciTech, 2022)

Implementing the Design of Experiments (DoE) Concept into the Development Phase of Orodispersible Minitablets (ODMTs) Containing Melatonin - Arkadiusz Hejduk; Michał Teżyk; Emilia Jakubowska; Klaudia Krüger; Janina Lulek (AAPS PharmSciTech, 2022)
Development of orodispersible minitablets (ODMTs) requires consideration of aspects related to small dimensions, while ensuring short disintegration time with sufficient mechanical stability. In order to meet these and other critical quality attributes (CQAs), quality by design is encouraged. According to this approach, formulation and compression process factors were systematically studied using design of experiments (Plackett-Burman for screening purposes, full and fractional factorial design for in-depth characterization) to understand their influence on CQAs of orodispersible minitablets containing melatonin. Mathematical models describing the relationships between processing variables and attributes such as resistance to crushing and disintegration time were successfully developed, characterized by high coefficients of determination ( R 2 adj = 0.90–0.97) and prediction errors in the range (+2.4 to −10.8%). In conclusion, based on these models, the design space was created for melatonin ODMTs, ensuring the product’s quality and process robustness. Moreover, the study demonstrated the suitability of texture analysis as an alternative to compendial measurement methods of resistance to crushing and disintegration time.

Optimization of Spray-Drying Process Parameters to Study Anti-Sticking Effect of Hydroxypropyl Methyl Cellulose-VLV on Corni fructus Extracts - Hong Cheng; Chenghao Lu; Gangfeng Xu; Lijie Zhao; Min Lu; Youjie Wang (AAPS PharmSciTech, 2022)

Transdermal Enhancement Strategy of Lappaconitine: Alteration of Keratin Configuration by Counter-Ion - Mingxin Li; Chao Liu; Yu Cai; Haoyuan Song; Liang Fang (AAPS PharmSciTech, 2022)

Design of a Long-Acting Rivastigmine Transdermal Delivery System: Based on Computational Simulation - Xue Han; Jingchuan Liu; Xiaoyue Hu; Wei Wang; Qing Wang (AAPS PharmSciTech, 2022)

Simplified Model-Dependent and Model-Independent Approaches for Dissolution Profile Comparison for Oral Products: Regulatory Perspective for Generic Product Development - Sivacharan Kollipara; Rajkumar Boddu; Tausif Ahmed; Siddharth Chachad (AAPS PharmSciTech, 2022)

Optimization and Application of an Efficient and Stable Inhalation Exposure System for Rodents - Zi Fan; Bo Zhou; Yujia Liu; Wu Sun; Yuntao Fang; Hongguo Lu; Dongya Chen; Kuikui Lu; Xinyue Wu; Tian Xiao; Wenjing Xie; Qian Bian (AAPS PharmSciTech, 2022)

Transdermal Delivery of Curcumin-Loaded Solid Lipid Nanoparticles as Microneedle Patch: an In Vitro and In Vivo Study - Ankitha Prabhu; Jobin Jose; Lalit Kumar; S Salwa; M Vijay Kumar; Seyed Mohammad Nabavi (AAPS PharmSciTech, 2022)

Assessment of Abrasion-Induced Visual Defects in Twin Screw Wet Granulation Using Wall Friction Measurements - Judith Menth; Martin Maus; Karl G. Wagner (AAPS PharmSciTech, 2022)
Starting point of the presented study were abrasion effects occurring during a twin screw wet granulation (TSG) process of a new chemical entity (NCE) formulation, resulting in gray spots on the final tablets. Several actions and systematic changes of equipment and process parameter settings of TSG process were conducted which reduced the visual defect rate of the tablets, i.e., gray spots on the surface, below the specification limit. To understand the rationale and mechanism behind these improvements, correlations of defect rates and wall friction measurements using a Schulze ring shear tester were evaluated. To check the suitability of the method, a broad range of wall materials as well as powder formulations at various moisture levels were investigated with regard to their wall friction angle. As differences in wall friction angle could be detected, further experiments were conducted using wall material samples made out of different screw materials for TSG. Evaluation of these screw wall material samples gave first hints, which screw materials should be preferred in regard of friction for TSG process. In the finally presented case study, wall friction measurements were performed using the above mentioned NCE formulation with known abrasion issues at TSG processing. The results confirmed that changes which led to a reduced visual defect rate of tablets correlated with a decreased wall friction angle. The results suggest wall friction measurements as a potent tool for equipment selection and establishment of a suitable process window prior to conducting TSG experiments. Graphical abstract

Transdermal Film Loaded with Avanafil Ultra-deformable Nanovesicles to Enhance its Percutaneous Absorption and Bioavailability - Omar D. Al-hejaili; Abdullah A. Alamoudi; Osama A. A. Ahmed; Khalid M. El-Say (AAPS PharmSciTech, 2022)

Solid Dispersions of Gefitinib Prepared by Spray Drying with Improved Mucoadhesive and Drug Dissolution Properties - Wesam W. Mustafa; John Fletcher; Mouhamad Khoder; Raid G. Alany (AAPS PharmSciTech, 2022)
Gefitinib is a tyrosine kinase inhibitor that is intended for oral administration yet suffers poor bioavailability along with undesirable side effects. To enhance its solubility and allow colon targeting, gefitinib (ZD) and blends of different ratios of polymers (ternary dispersion) were prepared in organic solution, and solid dispersions were generated employing the spray drying (SD) technique. The methylmethacrylate polymer Eudragit S 100 was incorporated for colon targeting; polyvinylpyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) were utilised to improve the solubility of ZD. SEM, DSC, XRPD, FT-IR, dissolution and cytotoxicity studies were undertaken to characterise and evaluate the developed formulations. SEM images revealed that the rod-shaped crystals of ZD were transformed into collapsed spheres with smaller particle size in the spray-dried particles. DSC, FTIR and XRPD studies showed that ZD loaded in the spray-dried dispersions was amorphous. ZD dissolution and release studies revealed that while a significant ( P

Progress and Principle of Drug Nanocrystals for Tumor Targeted Delivery - Meng Bai; Mingshi Yang; Junbo Gong; Hui Xu; Zhenping Wei (AAPS PharmSciTech, 2022)

Characterization of the Morphological Nature of Hollow Spray Dried Dispersion Particles Using X-ray Submicron-Computed Tomography - John F. Gamble; Mike Tobyn; Shawn Zhang; Aiden Zhu; Jakub Šalplachta; Jan Matula; Tomáš Zikmund; Jozef Kaiser; Peter Oberta (AAPS PharmSciTech, 2022)

Effect of Manufacturing Process on the Retention of Abuse-Deterrent Properties of PEO-Matrix Tablets - Leyla Rezaei; Saikishore Meruva; Maureen D. Donovan (AAPS PharmSciTech, 2022)

A Customized Screening Tool Approach for the Development of a Self-Nanoemulsifying Drug Delivery System (SNEDDS) - Fabian-Pascal Schmied; Alexander Bernhardt; Andrea Engel; Sandra Klein (AAPS PharmSciTech, 2022)
The present study focused on establishing a novel, (pre-)screening approach that enables the development of promising performing self-nanoemulsifying drug delivery systems (SNEDDSs) with a limited number of experiments. The strategic approach was based on first identifying appropriate excipients (oils/lipids, surfactants, and co-solvents) providing a high saturation solubility for lipophilic model compounds with poor aqueous solubility. Excipients meeting these requirements were selected for SNEDDS development, and a special triangular mixture design was applied for determining excipient ratios for the SNEDDS formulations. Celecoxib and fenofibrate were used as model drugs. Formulations were studied applying a specific combination of in vitro characterization methods. Specifications for a promising SNEDDS formulation were self-imposed: a very small droplet size ( PDI 99% in comparison with purified water). Excipients that provided a nanoemulsion after dispersion were combined, and ratios were optimized using a customized mapping method in a triangular mixture design. The best performing formulations were finally studied for their in vitro release performance. Results of the study demonstrate the efficiency of the customized screening tool approach. Since it enables successful SNEDDS development in a short time with manageable resources, this novel screening tool approach could play an important role in future SNEDDS development.

Orally Disintegrating Tablet Manufacture via Direct Powder Compression Using Cellulose Nanofiber as a Functional Additive - Shohei Nakamura; Tomomi Fukai; Takatoshi Sakamoto (AAPS PharmSciTech, 2022)

Preparation and Evaluation of rhINF-α-2b Sodium Hyaluronate Cross-Linked Porous Microspheres: Characterization, Sustained-Release Properties, and Antitumor Activity - Hongfei Liu; Yi Zou; Jie Zhu; Haibing He; Yingshu Feng; Caleb Kesse Firempong; Yang Yu; Changshan Sun (AAPS PharmSciTech, 2022)

Preparation and Anti-tumor Study of Dextran 70,000-Selenium Nanoparticles and Poloxamer 188-Selenium Nanoparticles - Zhenzhen Wang; Liyuan Ji; Yimeng Ren; Menghan Liu; Xiaoyu Ai; Cheng Yang (AAPS PharmSciTech, 2022)

Correction to: Primaquine Loaded Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), and Nanoemulsion (NE): Effect of Lipid Matrix and Surfactant on Drug Entrapment, in vitro Release, and ex vivo Hemolysis - Kai-Wei Wu; Corinne Sweeney; Narendar Dudhipala; Prit Lakhani; Narayan D. Chaurasiya; Babu L. Tekwani; Soumyajit Majumdar (AAPS PharmSciTech, 2022)

Strategies for Liposome Drug Delivery Systems to Improve Tumor Treatment Efficacy - Jia Wang; Junbo Gong; Zhenping Wei (AAPS PharmSciTech, 2022)

In Vivo and In Vitro Taste Assessment of Artesunate-Mefloquine, Praziquantel, and Benznidazole Drugs for Neglected Tropical Diseases and Pediatric Patients - Janine Boniatti; Marcelo R. R. Tappin; Rafaela G. da S Teixeira; Tamires de A V Gandos; Luis P. S. Rios; Izabelle A. M. Ferreira; Karina C. Oliveira; Sabrina Calil-Elias; Aila K. M. Santana; Laís B. da Fonseca; Flavio M. Shimizu; Olívia Carr; et al. (AAPS PharmSciTech, 2022)

Metamorphosis of Twin Screw Extruder-Based Granulation Technology: Applications Focusing on Its Impact on Conventional Granulation Technology - Rajat Radhakrishna Rao; Abhijeet Pandey; Aswathi R. Hegde; Vijay Induvadan Kulkarni; Chetan Chincholi; Vinay Rao; Indu Bhushan; Srinivas Mutalik (AAPS PharmSciTech, 2022)
In order to be at pace with the market requirements of solid dosage forms and regulatory standards, a transformation towards systematic processing using continuous manufacturing (CM) and automated model-based control is being thought through for its fundamental advantages over conventional batch manufacturing. CM eliminates the key gaps through the integration of various processes while preserving quality attributes via the use of process analytical technology (PAT). The twin screw extruder (TSE) is one such equipment adopted by the pharmaceutical industry as a substitute for the traditional batch granulation process. Various types of granulation techniques using twin screw extrusion technology have been explored in the article. Furthermore, individual components of a TSE and their conjugation with PAT tools and the advancements and applications in the field of nutraceuticals and nanotechnology have also been discussed. Thus, the future of granulation lies on the shoulders of continuous TSE, where it can be coupled with computational mathematical studies to mitigate its complications.

The Identification of Quality Risk Factors for Non-biological Complex Drugs and Epilepsy Drugs Using Statistical Analysis of Formulation-Based Recalls in the USA - Emily A. Kerstiens; Stephen R. Byrn; Kari L. Clase (AAPS PharmSciTech, 2022)

Spherical Agglomerates of Lactose Reduce Segregation in Powder Blends and Improve Uniformity of Tablet Content at High Drug Loads - Dejan Lamešić; Blaž Grilc; Robert Roškar; Selina Kolokytha; Jürgen Hofmann; Andreas Malekos; Rolf Kaufmann; Odon Planinšek (AAPS PharmSciTech, 2022)

A Compact Model for Lyophilizer Equipment Capability Estimation - Petr Kazarin; William Kessler; Emily Gong; Seongkyu Yoon; Huolong Liu; Richard Marx; Robin Bogner; Alina Alexeenko (AAPS PharmSciTech, 2022)

Fabrication of Stable Apigenin Nanosuspension with PEG 400 as Antisolvent for Enhancing the Solubility and Bioavailability - Renjie Xu; Cuiping Jiang; Lijing Zhou; Bin Li; Yi Hu; Yujie Guo; Xuecheng Xiao; Shan Lu (AAPS PharmSciTech, 2022)

Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain - Nkafu Bechem Ndemazie; Andriana Inkoom; Ellis Fualefeh Morfaw; Taylor Smith; Monica Aghimien; Dexter Ebesoh; Edward Agyare (AAPS PharmSciTech, 2022)
Drug delivery into the brain has for long been a huge challenge as the blood–brain barrier (BBB) offers great resistance to entry of foreign substances (with drugs inclusive) into the brain. This barrier in healthy individuals is protective to the brain, disallowing noxious substances present in the blood to get to the brain while allowing for the exchange of small molecules into the brain by diffusion. However, BBB is disrupted under certain disease conditions, such as cerebrovascular diseases including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders including multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and cancers. This review aims to provide a broad overview of present-day strategies for brain drug delivery, emphasizing novel delivery systems. Hopefully, this review would inspire scientists and researchers in the field of drug delivery across BBB to uncover new techniques and strategies to optimize drug delivery to the brain. Considering the anatomy, physiology, and pathophysiological functioning of the BBB in health and disease conditions, this review is focused on the controversies drawn from conclusions of recently published studies on issues such as the penetrability of nanoparticles into the brain, and whether active targeted drug delivery into the brain could be achieved with the use of nanoparticles. We also extended the review to cover novel non-nanoparticle strategies such as using viral and peptide vectors and other non-invasive techniques to enhance brain uptake of drugs. Graphical abstract

Sialic Acid Conjugated Chitosan Nanoparticles: Modulation to Target Tumour Cells and Therapeutic Opportunities - Rafquat Rana; Sarita Rani; Vipin Kumar; Kartik T. Nakhate; Ajazuddin; Umesh Gupta (AAPS PharmSciTech, 2022)

Developing a Biorelevant Dissolution Method for an Extrudable Core System (ECS) Osmotic Tablet - Raymond Chen; Andrew Blanchard; Joseph Kushner; Brent Harrington; Jia Liu; Vincent DeMatteo (AAPS PharmSciTech, 2022)

Development, Characterization, and Optimization of a Novel Abiraterone Acetate Formulation to Improve Biopharmaceutical Attributes Aided by Pharmacokinetic Modelling - Sandeep Dahiya; Ketan Savjani; Jignasa Savjani (AAPS PharmSciTech, 2022)

Quantification of Compatibility Between Polymeric Excipients and Atenolol Using Principal Component Analysis and Hierarchical Cluster Analysis - Barbara Rojek; Maria Gazda; Marek Wesolowski (AAPS PharmSciTech, 2022)
An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients can be selected, among others, by compatibility studies since incompatibilities between ingredients of the drug formulations adversely affect their bioavailability, stability, efficacy, and safety. Therefore, new, fast, and reliable methods for detecting incompatibility are constantly being sought. Hence, the purpose of this work was to assess the usefulness of a heating, cooling, and reheating differential scanning calorimetry (DSC) program for detecting potential incompatibilities between atenolol, an active pharmaceutical ingredient (API), and polymeric excipients. Hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used as supporting techniques. Additionally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) served as tools to support the interpretation of the data acquired from the DSC curves and FTIR spectra. As the alterations in the shape of the DSC peak of atenolol which are indicative of incompatibility are visible only on the cooling and reheating curves of the mixtures, the DSC heating–cooling–reheating program was found to be very useful for identifying potential incompatibilities in the binary mixtures of atenolol and polymeric excipients. The melting and recrystallization of atenolol alone and in its mixtures were also confirmed by HSM, while FTIR displayed changes in the spectra of mixtures due to incompatibility. These studies revealed that atenolol is incompatible with hydroxyethylcellulose, hypromellose, and methylcellulose. PXRD measurements at room temperature revealed that the crystallinity of atenolol did not change in these mixtures. However, its crystallinity was reduced in the mixtures previously heated up to 155 °C and then cooled to 25 °C. Graphical abstract

Inclusion Complexes of Daidzein with Cyclodextrin-Based Metal–Organic Framework-1 Enhance Its Solubility and Antioxidant Capacity - Yutaka Inoue; Masaaki Yoshida; Toshinari Ezawa; Takashi Tanikawa; Florencio Arce; Gerard Lee See; Junki Tomita; Mitsuaki Suzuki; Toshio Oguchi (AAPS PharmSciTech, 2022)

The Influence of Relative Humidity and Storage Conditions on the Physico-chemical Properties of Inhalation Grade Fine Lactose - Milica Stankovic-Brandl; Sarah Zellnitz; Paul Wirnsberger; Mirjam Kobler; Amrit Paudel (AAPS PharmSciTech, 2022)

Novel Co-crystals and Eutectics of Febuxostat: Characterization, Mechanism of Formation, and Improved Dissolution - Moksh Jagia; Dnyaneshwar P. Kale; Arvind Kumar Bansal; Sarsvatkumar Patel (AAPS PharmSciTech, 2021)

Scrutinizing the Feasibility of Nonionic Surfactants to Form Isotropic Bicelles of Curcumin: a Potential Antiviral Candidate Against COVID-19 - Dina B. Mahmoud; Mohamed Mofreh Bakr; Ahmed A. Al-karmalawy; Yassmin Moatasim; Ahmed El Taweel; Ahmed Mostafa (AAPS PharmSciTech, 2021)
Investigating bicelles as an oral drug delivery system and exploiting their structural benefits can pave the way to formulate hydrophobic drugs and potentiate their activity. Herein, the ability of non-ionic surfactants (labrasol ® , tween 80, cremophore EL and pluronic F127) to form curcumin loaded bicelles with phosphatidylcholine, utilizing a simple method, was investigated. Molecular docking was used to understand the mechanism of bicelles formation. The % transmittance and TEM exhibited bicelles formation with labrasol ® and tween 80, while cremophor EL and pluronic F127 tended to form mixed micelles. The surfactant-based nanostructures significantly improved curcumin dissolution (99.2 ± 2.6% within 10 min in case of tween 80-based bicelles) compared to liposomes and curcumin suspension in non-sink conditions. The prepared formulations improved curcumin ex vivo permeation over liposomes and drug suspension. Further, the therapeutic antiviral activity of the formulated curcumin against SARS-CoV-2 was potentiated over drug suspension. Although both Labrasol ® and tween 80 bicelles could form bicelles and enhance the oral delivery of curcumin when compared to liposomes and drug suspension, the mixed micelles formulations depicted superiority than bicelles formulations. Our findings provide promising formulations that can be utilized for further preclinical and clinical studies of curcumin as an antiviral therapy for COVID-19 patients.

Solubility Study of Acetylsalicylic Acid in Ethanol + Water Mixtures: Measurement, Mathematical Modeling, and Stability Discussion - Ali Nokhodchi; Taravat Ghafourian; Nour Nashed; Kofi Asare-Addo; Elmira Behboudi; Yasaman Sefid-Sefidehkhan; Aynaz Zarghampour; Elaheh Rahimpour; Abolghasem Jouyban (AAPS PharmSciTech, 2021)
Solubility determination of poorly water-soluble drugs is pivotal for formulation scientists when they want to develop a liquid formulation. Performing such a test with different ratios of cosolvents with water is time-consuming and costly. The scarcity of solubility data for poorly water-soluble drugs increases the importance of developing correlation and prediction equations for these mixtures. Therefore, the aim of the current research is to determine the solubility of acetylsalicylic acid in binary mixtures of ethanol+water at 25 and 37°C. Acetylsalicylic acid is non-stable in aqueous solutions and readily hydrolyze to salicylic acid. So, the solubility of acetylsalicylic acid is measured in ethanolic mixtures by HPLC to follow the concentration of produced salicylic acid as well. Moreover, the solubility of acetylsalicylic acid is modeled using different cosolvency equations. The measured solubility data were also predicted using PC-SAFT EOS model. DSC results ruled out any changes in the polymorphic form of acetylsalicylic acid after the solubility test, whereas XRPD results showed some changes in crystallinity of the precipitated acetylsalicylic acid after the solubility test. Fitting the solubility data to the different cosolvency models showed that the mean relative deviation percentage for the Jouyban-Acree model was less than 10.0% showing that this equation is able to obtain accurate solubility data for acetylsalicylic acid in mixtures of ethanol and water. Also, the predicted data with an average mean relative deviation percentage ( MRD %) of less than 29.65% show the capability of the PC-SAFT model for predicting solubility data. A brief comparison of the solubilities of structurally related solutes to acetylsalicylic acid was also provided.

Preparation and Characterization of Stable Amorphous Glassy Solution of BCS II and IV Drugs - Sathish Dharani; Khaldia Sediri; Phillip Cook; Rajendran Arunagiri; Mansoor A. Khan; Ziyaur Rahman (AAPS PharmSciTech, 2021)

In Situ Liquid Crystal Gel as a Promising Strategy for Improving Ocular Administration of Dexamethasone: Preparation, Characterization, and Evaluation - Wenqing Wu; Wenxuan Cao; Jingbao Chen; Ye Cai; Baoqi Dong; Xiaoqin Chu (AAPS PharmSciTech, 2021)

Formulation and Evaluation of Topical Biodegradable Films Loaded with Levofloxacin Lipid Nanocarriers - Rania S. Abdel-Rashid; Eman S. El-leithy; Raghda Abdel-monem (AAPS PharmSciTech, 2021)

RETRACTED ARTICLE: Bimatoprost-Loaded Silica Shell–Coated Nanoparticles-Laden Soft Contact Lenses to Manage Glaucoma: In Vitro and In Vivo Studies - He Xiaojie; Jiang Fagang; Jing Jun; Wang Chunfang; Li Chengquan; Wang Xinghua (AAPS PharmSciTech, 2021)

Nanostructured Lipid Carriers as a Novel Strategy for Topical Antifungal Therapy - Naiane Carvalho Nogueira; Laisa Lis Fontinele de Sá; André Luis Menezes de Carvalho (AAPS PharmSciTech, 2021)

Optimization of Spray-Drying Parameters for Formulation Development at Preclinical Scale - Marika Nespi; Robert Kuhn; Chun-Wan Yen; Joseph W. Lubach; Dennis Leung (AAPS PharmSciTech, 2021)

Unexplored Excipients in Biotherapeutic Formulations: Natural Osmolytes as Potential Stabilizers Against Thermally Induced Aggregation of IgG1 Biotherapeutics - Purva P. Bhojane; Srishti Joshi; Sushree Jagriti Sahoo; Anurag S. Rathore (AAPS PharmSciTech, 2021)

Vitamin E Oil Incorporated Liposomal Melphalan and Simvastatin: Approach to Obtain Improved Physicochemical Characteristics of Hydrolysable Melphalan and Anticancer Activity in Combination with Simvastatin Against Multiple Myeloma - Unnam Sambamoorthy; Arehalli S. Manjappa; Bhanoji Rao Muddana Eswara; Arun Kumar Sanapala; Naidu Nagadeepthi (AAPS PharmSciTech, 2021)

Advances in Delivery of Chemotherapeutic Agents for Cancer Treatment - Asmita Yadav; Sakshi Singh; Harmik Sohi; Shweta Dang (AAPS PharmSciTech, 2021)

Increase in Dissolution Rate of Zotepine via Nanomilling Process — Impact of Dried Nanocrystalline Suspensions on Bioavailability - Komal Parmar; Kirti Oza (AAPS PharmSciTech, 2021)

In Vitro Modeling of Skin Barrier Disruption and its Recovery by Ceramide-Based Formulations - Barbora Amélie Čuříková-Kindlová; Aneta Vovesná; Anna Nováčková; Jarmila Zbytovská (AAPS PharmSciTech, 2021)

A Novel Computational Approach Coupled with Machine Learning to Predict the Extent of Agglomeration in Particulate Processes - Kushal Sinha; Eric Murphy; Prashant Kumar; Kirsten A. Springer; Raimundo Ho; Nandkishor K. Nere (AAPS PharmSciTech, 2021)

Immunological Assessment of Chitosan or Trimethyl Chitosan-Coated PLGA Nanospheres Containing Fusion Antigen as the Novel Vaccine Candidates Against Tuberculosis - Sirwan Zare; Mona Kabiri; Yousef Amini; Adel Najafi; Fatemeh Mohammadpour; Seyed Hasan Ayati; Amin Reza Nikpoor; Mohsen Tafaghodi (AAPS PharmSciTech, 2021)

Recent Advances in Enhancement of Dissolution and Supersaturation of Poorly Water-Soluble Drug in Amorphous Pharmaceutical Solids: A Review - Qin Shi; Fang Li; Stacy Yeh; Sakib M. Moinuddin; Junbo Xin; Jia Xu; Hao Chen; Bai Ling (AAPS PharmSciTech, 2021)

Development, Optimization, and Pharmacokinetics Study of Bufalin/Nintedanib Co-loaded Modified Albumin Sub-microparticles Fabricated by Coaxial Electrostatic Spray Technology - Peng Chen; Shengzhe Lu; Bin Pan; Ying Xu (AAPS PharmSciTech, 2021)

Intra-articular Injection of Lornoxicam and MicroRNA-140 Co-loaded Cationic Liposomes Enhanced the Therapeutic Treatment of Experimental Osteoarthritis - Kongfang He; Xiaoyu Huang; Rumeng Shan; Xuehua Yang; Ruonan Song; Fei Xie; Guihua Huang (AAPS PharmSciTech, 2021)

3D Printed Personalized Medicine for Cancer: Applications for Betterment of Diagnosis, Prognosis and Treatment - Harshada Bhuskute; Pravin Shende; Bala Prabhakar (AAPS PharmSciTech, 2021)

Transfersomes: a Revolutionary Nanosystem for Efficient Transdermal Drug Delivery - Muhammad Waseem Akram; Humzah Jamshaid; Fiza Ur Rehman; Muhammad Zaeem; Jehan zeb Khan; Ahmad Zeb (AAPS PharmSciTech, 2021)

RETRACTED ARTICLE: Ofloxacin-Loaded Niosome-Laden Contact Lens: Improved Properties of Biomaterial for Ocular Drug Delivery - Jiayong Liu; Xue Wang (AAPS PharmSciTech, 2021)

Budding Multi-matrix Technology—a Retrospective Approach, Deep Insights, and Future Perspectives - Anitha Sriram; Suma Tangirala; Srividya Atmakuri; Sajid Hoque; Sheela Modani; Saurabh Srivastava; Srushti Mahajan; Indrani Maji; Rahul Kumar; Dharmendra Khatri; Jitender Madan; Pankaj Kumar Singh (AAPS PharmSciTech, 2021)

Preformulation Studies to Guide the Production of Medicines by Fused Deposition Modeling 3D Printing - Ludmila A. G. Pinho; Ana Luiza Lima; Livia L. Sa-Barreto; Tais Gratieri; Guilherme M. Gelfuso; Ricardo Neves Marreto; Marcilio Cunha-Filho (AAPS PharmSciTech, 2021)

Correction to: Piperine-Loaded Glycyrrhizic Acid- and PLGA-Based Nanoparticles Modified with Transferrin for Antitumor - Shuang Li; Jueshuo Guo; Zonghua Tian; Jing Chen; Guojing Gou; Yang Niu; Li Li; Jianhong Yang (AAPS PharmSciTech, 2021)

Preparation and Characterization of pH-Independent Sustained-Release Tablets Containing Hot Melt Extruded Solid Dispersions of Clarithromycin - Qazi Amir Ijaz; Sumera Latif; Qurat-ul-ain Shoaib; Memoona Rashid; Muhammad Sohail Arshad; Amjad Hussain; Nadeem Irfan Bukhari; Sohail Riaz; Nasir Abbas (AAPS PharmSciTech, 2021)

A Software Tool for Lyophilization Primary Drying Process Development and Scale-up Including Process Heterogeneity, I: Laboratory-Scale Model Testing - Robin Bogner; Emily Gong; William Kessler; Michael Hinds; Arushi Manchanda; Seongkyu Yoon; Huolong Liu; Richard Marx; Jessie Zhao; Puneet Sharma; Akhilesh Bhambhani; Justin Stanbro; et al. (AAPS PharmSciTech, 2021)

A Practical Discussion on Estimating Shelf Life Through Tolerance Intervals - James Schwenke; Patrick Forenzo; Walter Stroup; Michelle Quinlan (AAPS PharmSciTech, 2021)

Development and Optimization of Microballoons Assisted Floating Tablets of Baclofen - Pradipkumar Wavhule; Padma V. Devarajan (AAPS PharmSciTech, 2021)

Highlighting DEM’s Potential to Gauge Mechanistic Attributes of MUPS Tablet and Capsule Formulations - Shishir Shekhar; Negin Amini; David A. V. Morton; Karen P. Hapgood; Alexander Russell (AAPS PharmSciTech, 2021)

AddaVax Formulated with PolyI:C as a Potential Adjuvant of MDCK-based Influenza Vaccine Enhances Local, Cellular, and Antibody Protective Immune Response in Mice - Xuanxuan Nian; Jiayou Zhang; Tao Deng; Jing Liu; Zheng Gong; Chuanshuo Lv; Luyao Yao; Junying Li; Shihe Huang; Xiaoming Yang (AAPS PharmSciTech, 2021)
Poor immune responses to inactivated influenza vaccine can be improved by effective and safe adjuvants to increase antibody titers and cellular protective response. In our study, AddaVax and PolyI:C combined adjuvant (AP adjuvant) were used for influenza vaccine development. After immunizing BALB/c mice and Wistar rats intramuscularly, Split inactivated H3N2 vaccine adjuvanted with AP elicited higher serum hemagglutination-inhibition antibodies and IgG titers. We demonstrated that AP induced a transient innate immune cytokines production at the injection site, induced H3N2 uptake by DCs, increased recruitment of monocytes and DCs in LNs, and promoted H3N2 vaccine migration; AP facilitated vaccines to induce a vigorous adaptive immune response. Besides, AP showed good safety as shown by lymph nodes (LNs) size, spleens index of BALB/c mice, and weight changes and C-reaction protein level of BALB/c mice and Wistar rats after repeated administration of high-dose vaccine with or without adjuvant. These findings indicate that AP is a potential novel adjuvant and can be used as a safe and effective adjuvant for MDCK-based influenza inactivated vaccine to induce cellular and antibody protective response.

Brucine-Loaded Ethosomal Gel: Design, Optimization, and Anti-inflammatory Activity - Marwa H. Abdallah; Amr S. Abu Lila; Rahamat Unissa; Heba S. Elsewedy; Hanaa A. Elghamry; Mahmoud S. Soliman (AAPS PharmSciTech, 2021)

A Novel Method for Rapid Particle Size Analysis of Ibuprofen Using Near-infrared Spectroscopy - Monika Stojanovska Pecova; Nikola Geskovski; Gjorgji Petrushevski; Petre Makreski (AAPS PharmSciTech, 2021)

Design and Characterization of HY-038 Solid Dispersions via Spray Drying Technology: In Vitro and In Vivo Evaluations - Taotao Jiang; Limei Han; Enhao Lu; Wenxiu He; Shilin Du; Xianyi Sha (AAPS PharmSciTech, 2021)

Recommended Best Practices for Lyophilization Validation 2021 Part II: Process Qualification and Continued Process Verification - Feroz Jameel; Alina Alexeenko; Akhilesh Bhambhani; Gregory Sacha; Tong Zhu; Serguei Tchessalov; Puneet Sharma; Ehab Moussa; Lavanya Iyer; Sumit Luthra; Jayasree Srinivasan; Ted Tharp; et al. (AAPS PharmSciTech, 2021)
This work describes the lyophilization process validation and consists of two parts. Part one (Part I: Process Design and Modeling) focuses on the process design and is described in the previous paper, while the current paper is devoted to process qualification and continued process verification. The goal of the study is to show the cutting edge of lyophilization validation based on the integrated community-based opinion and the industrial perspective. This study presents best practices for batch size determination and includes the effect of batch size on drying time, process parameters selection strategies, and batch size overage to compensate for losses during production. It also includes sampling strategies to demonstrate batch uniformity as well as the use of statistical models to ensure adequate sampling. Based on the LyoHUB member organizations survey, the best practices in determining the number of PPQ runs are developed including the bracketing approach with minimum and maximum loads. Standard practice around CQA and CPP selection is outlined and shows the advantages of using control charts and run charts for process trending and quality control. The case studies demonstrating the validation strategy for monoclonal antibody and the impact of the loading process on the lyophilization cycle and product quality as well as the special case of lyophilization for dual-chamber cartridge system are chosen to illustrate the process validation. The standard practices in the validation of the lyophilization process, special lyophilization processes, and their impact on the validation strategy are discussed. Graphical Abstract

Interrelationships Between Coating Uniformity and Efficiency in Pan Coating Processes - Michael Choi; Stuart C. Porter; Axel Meisen (AAPS PharmSciTech, 2021)

Quick and Simultaneous Analysis of Dissolved Active Pharmaceutical Ingredients and Formulation Excipients from the Dissolution Test Utilizing UHPLC and Charged Aerosol Detector - Mariko Kimoto; Toshiyasu Sakane; Hidemasa Katsumi; Akira Yamamoto (AAPS PharmSciTech, 2021)

Enhancing Biopharmaceutical Attributes of Khellin by Amorphous Binary Solid Dispersions - Sonali S. Bharate (AAPS PharmSciTech, 2021)

Low-Frequency Sonophoresis as an Active Approach to Potentiate the Transdermal Delivery of Agomelatine-Loaded Novasomes: Design, Optimization, and Pharmacokinetic Profiling in Rabbits - Mai Ahmed Tawfik; Magdy Ibrahim Mohamed; Mina Ibrahim Tadros; Sara Nageeb El-Helaly (AAPS PharmSciTech, 2021)

Cliv-92-Loaded Glycyrrhetinic Acid-Modified Chitosan Nanoparticles for Enhanced Hepatoprotection–Preparation, Characterization, and In Vivo Evaluation - Kuldeep Singh Yadav; Nidhi Srivastava; Vineet Kumar Rai; Ranjana; Sudeep Tandon; Pooja Rani Mina; Debabrata Chanda; Navodayam Kalleti; Srikanta Kumar Rath; Mahendra Pandurang Darokar; P. V. Ajayakumar; Karuna Shanker; et al. (AAPS PharmSciTech, 2021)

Investigation of the Fused Deposition Modeling Additive Manufacturing I: Influence of Process Temperature on the Quality and Crystallinity of the Dosage Forms - Jiaxiang Zhang; Rishi Thakkar; Vineet R. Kulkarni; Yu Zhang; Anqi Lu; Mohammed Maniruzzaman (AAPS PharmSciTech, 2021)

Correction to: Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine - Pan Gao; Zhujun Jiang; Qiao Luo; Chengqiao Mu; Mengsuo Cui; Xinggang Yang (AAPS PharmSciTech, 2021)

Correction to: Recommended Best Practices for Lyophilization Validation—2021 Part I: Process Design and Modeling - Feroz Jameel; Alina Alexeenko; Akhilesh Bhambhani; Gregory Sacha; Tong Zhu; Serguei Tchessalov; Lokesh Kumar; Puneet Sharma; Ehab Moussa; Lavanya Iyer; Rui Fang; Jayasree Srinivasan; et al. (AAPS PharmSciTech, 2021)

Development of Self-Microemulsifying Drug Delivery System to Improve Nisoldipine Bioavailability: Cell Line and In Vivo Evaluations - Veenu P. Mundada; Mitali H. Patel; Piyush K. Mundada; Krutika K. Sawant (AAPS PharmSciTech, 2021)

Effects of Formulation and Manufacturing Process on Drug Release from Solid Self-emulsifying Drug Delivery Systems Prepared by High Shear Mixing - Gustavo Parreira Araújo; Felipe Terra Martins; Stephânia Fleury Taveira; Marcílio Cunha-Filho; Ricardo Neves Marreto (AAPS PharmSciTech, 2021)

Thiolated Chitosan-Centella asiatica Nanocomposite: A Potential Brain Targeting Strategy Through Nasal Route - Hajira Banu Haroon; Dhrubojyoti Mukherjee; Jayaraman Anbu; Banala Venkatesh Teja (AAPS PharmSciTech, 2021)

Amalgamation of Solid Dispersion and Melt Adsorption Technique: Improved In Vitro and In Vivo Performance of Ticagrelor Tablets - Mukesh Yadav; Jayant Sarolia; Bhavin Vyas; Manisha Lalan; Shubhada Mangrulkar; Pranav Shah (AAPS PharmSciTech, 2021)

Fabrication and Evaluation of Transdermal Delivery of Carbamazepine Dissolving Microneedles - Rana Obaidat; Fatima BaniAmer; Shereen M. Assaf; Ahmed Yassin (AAPS PharmSciTech, 2021)

RETRACTED ARTICLE: Development and Evaluation of Icariin-Loaded PLGA-PEG Nanoparticles for Potentiation the Proapoptotic Activity in Pancreatic Cancer Cells - Nabil A. Alhakamy (AAPS PharmSciTech, 2021)

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine - Pan Gao; Zhujun Jiang; Qiao Luo; Chengqiao Mu; Mengsuo Cui; Xinggang Yang (AAPS PharmSciTech, 2021)

Dry Powder Mixing Is Feasible in Continuous Twin Screw Extruder: Towards Lean Extrusion Process for Oral Solid Dosage Manufacturing - Daniel Mateo-Ortiz; Vladimir Villanueva-Lopez; Shashank Venkat Muddu; Gregory D. Doddridge; Dana Alhasson; Michael C. Dennis (AAPS PharmSciTech, 2021)

Development and Optimization of Itraconazole-Loaded Solid Lipid Nanoparticles for Topical Administration Using High Shear Homogenization Process by Design of Experiments: In Vitro, Ex Vivo and In Vivo Evaluation - Neeraj Kumar; Shishu Goindi (AAPS PharmSciTech, 2021)

Development of a Controlled Continuous Low-Dose Feeding Process - Sara Fathollahi; Julia Kruisz; Stephan Sacher; Jakob Rehrl; M. Sebastian Escotet-Espinoza; James DiNunzio; Benjamin J. Glasser; Johannes G. Khinast (AAPS PharmSciTech, 2021)
This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum deviation from the set-point, even for materials that are typically difficult to accurately feed (e.g., due to high cohesion or low density) using conventional continuous feeders. Density variations observed during the feeding process were characterized via a displacement feed factor profile for each powder. The characterized effective displacement density profile was applied in the micro-feeder system to proactively control the feed rate by manipulating the powder displacement rate (i.e., computing the feed rate from the powder displacement rate). Based on the displacement feed factor profile, the feed rate can be predicted during the feeding process and at any feed rate set-point. Three pharmaceutically relevant materials were used for the micro-feeder evaluation: di-calcium phosphate (large-particle system, high density), croscarmellose sodium (small-particle system, medium density), and barium sulfate (very small-particle

Nanoemulsomes for Enhanced Oral Bioavailability of the Anticancer Phytochemical Andrographolide: Characterization and Pharmacokinetics - Manal A. Elsheikh; Samar A. Rizk; Yosra S. R. Elnaggar; Ossama Y. Abdallah (AAPS PharmSciTech, 2021)

Development and Optimization of Asenapine Sublingual Film Using QbD Approach - Rahil Dalal; Jigar Shah; Bapi Gorain; Hira Choudhury; Shery Jacob; Tejal A. Mehta; Hiral Shah; Anroop B. Nair (AAPS PharmSciTech, 2021)

Role of Permeability on the Biopredictive Dissolution of Amorphous Solid Dispersions - Gayathri Ramachandran; M. S. Sudheesh (AAPS PharmSciTech, 2021)

Lipopolysaccharide Nanosystems for the Enhancement of Oral Bioavailability - Mumuni Sumaila; Thashree Marimuthu; Pradeep Kumar; Yahya E. Choonara (AAPS PharmSciTech, 2021)

Improvement of Bleached Shellac as Enteric Coating by Composite Formation - Manee Luangtana-anan; Suthep Saengsod; Sontaya Limmatvapirat (AAPS PharmSciTech, 2021)

Primaquine Loaded Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), and Nanoemulsion (NE): Effect of Lipid Matrix and Surfactant on Drug Entrapment, in vitro Release, and ex vivo Hemolysis - Kai-Wei Wu; Corinne Sweeney; Narendar Dudhipala; Prit Lakhani; Narayan D. Chaurasiya; Babu L. Tekwani; Soumyajit Majumdar (AAPS PharmSciTech, 2021)

Investigation on Potential of Chitosan Nanoparticles for Oral Bioavailability Enhancement of Risedronate Sodium - Nikhil Suthar; Jagruti Desai; Hetal Paresh Thakkar (AAPS PharmSciTech, 2021)

Solvent-Assisted Hot Melt Extrusion of a Thermally Labile, High Melting Point Compound - C. Lagan; J. E. Huckle; J. M. Katz; B. Khorsand; D. Daurio; G. P. Andrews; J. Chung; F. Alvarez-Nunez (AAPS PharmSciTech, 2021)

Accelerated Stability Assessment Program to Predict Long-term Stability of Drugs: Application to Ascorbic Acid and to a Cyclic Hexapeptide - Pauline Legrand; Rabah Gahoual; Pascal Houzé; Sophie Dufaÿ (AAPS PharmSciTech, 2021)

Formulation of Chitosan-Coated Piperine NLCs: Optimization, In Vitro Characterization, and In Vivo Preclinical Assessment - Ameeduzzafar Zafar; Nabil K. Alruwaili; Syed Sarim Imam; Omar Awad Alsaidan; Khalid Saad Alharbi; Mohd Yasir; Mohammed Elmowafy; Elshaer F. Mohammed; Ziad H. Al-Oanzi (AAPS PharmSciTech, 2021)

Cyclodextrin Complex Formation with Water-Soluble Drugs: Conclusions from Isothermal Titration Calorimetry and Molecular Modeling - Karim S. Shalaby; Muhammad I. Ismail; Alf Lamprecht (AAPS PharmSciTech, 2021)
Cyclodextrin (CD) complexes are frequently used for enhancing the solubility or absorption of poorly water-soluble drugs. On the contrary, little is known about their complex formation with water-soluble drugs. Here, we have studied the interaction between 2-hydroxypropyl β-CD (HPβCD) and three water-soluble drugs, namely naloxone (NX), oxycodone (OC), and tramadol (TR), by isothermal titration calorimetry (ITC) combined with molecular modeling in view of the potential impact on drug release. The results showed that the complex formation of HPβCD with all three drugs occurs spontaneously. The complexes formed with NX and OC were found to be 2NX:1HPβCD and 3OC:2HPβCD, respectively. TR was found to form 2 complexes with HPβCD; of 1:2 and 1:1 complexation ratios. The binding of HPβCD to NX was greater than to OC due to the higher hydrophobicity of the structure of the former. Moreover, the binding affinity of HPβCD to TR was higher than to OC, which indicated the effect of the higher flexibility of the guest in increasing the binding affinity. In vitro drug release experiments from the various complexes revealed a significant impact of the stoichiometry of the complex on the release profiles. Accordingly, the co-administration of cyclodextrins with water-soluble drugs should be closely monitored, as it may result in unintentional complex formation that can potentially impact the drugs’ gastrointestinal absorption.

Non-intuitive Behavior of Polymer-Ciprofloxacin Nanoconjugate Suspensions: a Tool for Flexible Oral Drug Delivery - Amos Abioye; Maitham Naqvi; Dillan Pattni; Aderonke Ayinke Adepoju-Bello (AAPS PharmSciTech, 2021)

Local Treatment of Non-small Cell Lung Cancer with a Spray-Dried Bevacizumab Formulation - Kimberly B. Shepard; David T. Vodak; Philip J. Kuehl; David Revelli; Yue Zhou; Amanda M. Pluntze; Molly S. Adam; Julia C. Oddo; Lauren Switala; Jonathan L. Cape; John M. Baumann; Michael Banks (AAPS PharmSciTech, 2021)
Local delivery of biotherapeutics to the lung holds great promise for treatment of lung diseases, but development of physically stable, biologically active dry powder formulations of large molecules for inhalation has remained a challenge. Here, spray drying was used to manufacture a dry powder pulmonary formulation of bevacizumab, a monoclonal antibody approved to treat non-small cell lung cancer (NSCLC) by intravenous infusion. By reformulating bevacizumab for local delivery, reduced side effects, lower doses, and improved patient compliance are possible. The formulation had aerosol properties suitable for delivery to the deep lung, as well as good physical stability at ambient temperature for at least 6 months. Bevacizumab’s anti-VEGF bioactivity was not impacted by the manufacturing process. The formulation was efficacious in an in vivo rat model for NSCLC at a 10-fold decrease in dose relative to the intravenous control.

Salts and Polymorph Screens for Bedaquiline - Mercy Okezue; Susan Bogdanowich-Knipp; Daniel Smith; Matthias Zeller; Stephen Byrn; Pamela Smith; Dale K. Purcell; Kari Clase (AAPS PharmSciTech, 2021)
Bedaquiline is used to treat multi-resistant tuberculosis in adults. The fumarate salt is commercially available and used in the product Sirturo. To provide open access to bedaquiline molecule once the patent on the chemical substance expires, new salts were screened. This work offers additional information on the bedaquiline system, as new salts may present better pharmacokinetic properties. The current studies focus on the attempted isolation of the acetate, benzoate, benzenesulfonate, hydrobromide, succinate, hydrochloride, tartrate, lactate, maleate, malate, and mesylate salts of bedaquiline. Potential salts were screened using a unique combination of conventional screening, and small-scale experiments supplemented by crystallographic analysis and infrared microspectroscopy. Salts were prepared on a larger scale by dissolving 1:1 ratios of the individual salt formers and bedaquiline base (30 mg, 0.055 mmol) in different solvents and allowing the solutions to evaporate or crystallize. X-ray diffraction (XRD) techniques and spectroscopic and thermal analyses were employed to characterize the salts. The benzoate and maleate salts were selected as lead candidates after reviewing preliminary characterization data. To determine the most stable forms for the leads, a polymorph screen was conducted using solvents of various polarities. These salt screens successfully generated five new salts of bedaquiline, namely, benzoate, maleate, hydrochloride, besylate, and mesylate. The existence of these salts was confirmed by powder XRD, proton NMR, and IR spectroscopies. TGA and DSC thermal analysis along with hot-stage optical microscopy were further used to characterize the salts. The polymorph screen conducted on the salts suggested the absence of additional polymorphs at 1 g scale.

Altered Media Flow and Tablet Position as Factors of How Air Bubbles Affect Dissolution of Disintegrating and Non-disintegrating Tablets Using a USP 4 Flow-Through Cell Apparatus - Hiroyuki Yoshida; Keita Teruya; Yasuhiro Abe; Takayuki Furuishi; Kaori Fukuzawa; Etsuo Yonemochi; Ken-ichi Izutsu (AAPS PharmSciTech, 2021)

Glucose-Responsive Polyelectrolyte Complexes Based on Dendritic Mesoporous Silica for Oral Insulin Delivery - Tingting Qin; Libiao Yan; Xin Wang; Siqi Lin; Qingbing Zeng (AAPS PharmSciTech, 2021)

Batch Selection via In Vitro/In Vivo Correlation in Pharmacokinetic Bioequivalence Testing - Elise Burmeister Getz; Kevin J. Carroll; Johanna Mielke; Byron Jones; Leslie Z. Benet (AAPS PharmSciTech, 2021)

Performance of Multiple-Batch Approaches to Pharmacokinetic Bioequivalence Testing for Orally Inhaled Drug Products with Batch-to-Batch Variability - Elise Burmeister Getz; Kevin J. Carroll; J. David Christopher; Beth Morgan; Scott Haughie; Alessandro Cavecchi; Christopher Wiggenhorn; Hayden Beresford; Helen Strickland; Svetlana Lyapustina (AAPS PharmSciTech, 2021)
Batch-to-batch pharmacokinetic (PK) variability of orally inhaled drug products has been documented and can render single-batch PK bioequivalence (BE) studies unreliable; results from one batch may not be consistent with a repeated study using a different batch, yet the goal of PK BE is to deliver a product comparison that is interpretable beyond the specific batches used in the study. We characterized four multiple-batch PK BE approaches to improve outcome reliability without increasing the number of clinical study participants. Three approaches include multiple batches directly in the PK BE study with batch identity either excluded from the statistical model (“Superbatch”) or included as a fixed or random effect (“Fixed Batch Effect,” “Random Batch Effect”). A fourth approach uses a bio-predictive in vitro test to screen candidate batches, bringing the median batch of each product into the PK BE study (“Targeted Batch”). Three of these approaches (Fixed Batch Effect, Superbatch, Targeted Batch) continue the single-batch PK BE convention in which uncertainty in the Test/Reference ratio estimate due to batch sampling is omitted from the Test/Reference confidence interval. All three of these approaches provided higher power to correctly identify true bioequivalence than the standard single-batch approach with no increase in clinical burden. False equivalence (type I) error was inflated above the expected 5% level, but multiple batches controlled type I error better than a single batch. The Random Batch Effect approach restored 5% type I error, but had low power for small ( e.g. ,

Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies - Jinyan Wan; Yu Long; Songyu Liu; Yulu Zhang; Yan Xiang; Dan Li; Ai Shi; Yu Shuang; Ying Li; Yanan He; Nan Li; Yongmei Guan (AAPS PharmSciTech, 2021)

Recommended Best Practices for Lyophilization Validation—2021 Part I: Process Design and Modeling - Feroz Jameel; Alina Alexeenko; Akhilesh Bhambhani; Gregory Sacha; Tong Zhu; Serguei Tchessalov; Lokesh Kumar; Puneet Sharma; Ehab Moussa; Lavanya Iyer; Rui Fang; Jayasree Srinivasan; et al. (AAPS PharmSciTech, 2021)
This work describes lyophilization process validation and consists of two parts. Part I focuses on the process design and is described in the current paper, while part II is devoted to process qualification and continued process verification. The intent of these articles is to provide readers with recent updates on lyophilization validation in the light of community-based combined opinion on the process and reflect the industrial prospective. In this paper, the design space approach for process design is described in details, and examples from practice are provided. The approach shows the relationship between the process inputs; it is based on first principles and gives a thorough scientific understanding of process and product. The lyophilization process modeling and scale-up are also presented showing the impact of facility, equipment, and vial heat transfer coefficient. The case studies demonstrating the effect of batch sizes, fill volume, and dose strength to show the importance of modeling as well as the effect of controlled nucleation on product resistance are discussed. Graphical abstract

Preparation, Characterization, and In Vitro/In Vivo Evaluation of 3-O-β-D-Galactosylated Resveratrol-Loaded Polydopamine Nanoparticles - Beilei Wang; Xiaoxiao Shan; Shujie Lv; Liqiong Zha; Caiyun Zhang; Qiannian Dong; Weidong Chen (AAPS PharmSciTech, 2021)

Digital Image Disintegration Analysis: a Novel Quality Control Method for Fast Disintegrating Tablets - Osamah Malallah; Zara Rashid; Chee Lok Li; Abdulmalik Alqurshi; Mohamed A. Alhanan; Ben Forbes; Paul G. Royall (AAPS PharmSciTech, 2021)
Measuring tablet disintegration is essential for quality control purposes; however, no established method adequately accounts for the timeframe or small volumes of the medium associated with the dissipation process for fast disintegrating tablets (FDTs) in the mouth. We hypothesised that digital imaging to measure disintegration in a low volume of the medium might discriminate between different types of FTD formulation. A digital image disintegration analysis (DIDA) was designed to measure tablet disintegration in 0.05–0.7 mL of medium. A temperature-controlled black vessel was 3D-printed to match the dimensions of each tablet under investigation. An overhead camera recorded the mean grey value of the tablet as a measure of the percentage of the formulation which remained intact as a function of time. Imodium Instants, Nurofen Meltlets and a developmental freeze-dried pilocarpine formulation were investigated. The imaging approach proved effective in discriminating the disintegration of different tablets (p

Piperine-Loaded Glycyrrhizic Acid- and PLGA-Based Nanoparticles Modified with Transferrin for Antitumor - Shuang Li; Jueshuo Guo; Zonghua Tian; Jing Chen; Guojing Gou; Yang Niu; Li Li; Jianhong Yang (AAPS PharmSciTech, 2021)

Topical Application of Vitamin D3-Loaded Hybrid Nanosystem to Offset Imiquimod-Induced Psoriasis - Sudeep Sudesh Pukale; Anupama Mittal; Deepak Chitkara (AAPS PharmSciTech, 2021)