Stability Evaluation of Lyotropic Liquid Crystalline Precursor for the Co-delivery of Chlorhexidine and Silver Nanoparticles - Fangqin Fu; Xin Li; Tengyi Zheng; Xiao Xia; Minqun Du; Zhengwei Huang; Ying Huang; Xin Pan; Chuanbin Wu (AAPS PharmSciTech, 2021)

Pharmaceutical Applications of Quantum Dots - Aman Gour; Suman Ramteke; Narendra Kumar Jain (AAPS PharmSciTech, 2021)

Evaluation of the Antitumor Effect and Immune Response of Micelles Modified with a Polysialic Acid-d-α-Tocopheryl Polyethylene Glycol 1000 Succinate Conjugate - Jing Sun; Qingjing Tian; Min Liu; Yuqing Su; Xinrong Liu; Yihui Deng; Yanzhi Song (AAPS PharmSciTech, 2021)

RETRACTED ARTICLE: Sustained Delivery of Timolol Using Nanostructured Lipid Carriers-Laden Soft Contact Lenses - Chenfei Tian; Lu Zeng; Le Tang; Jingni Yu; Mei Ren (AAPS PharmSciTech, 2021)

Formulation, Optimization and Evaluation of Nanoparticulate Oral Fast Dissolving Film Dosage Form of Nitrendipine - Neha Vishal Gandhi; Uday Arvind Deokate; Sachidanand Shankar Angadi (AAPS PharmSciTech, 2021)

Biorelevant In Vitro Skin Permeation Testing and In Vivo Pharmacokinetic Characterization of Lidocaine from a Nonaqueous Drug-in-Matrix Topical System - Emileigh Greuber; Kip Vought; Kalpana Patel; Hiroaki Suzuki; Kazuhiro Usuda; Akira Shiramizu; Luana Pesco Koplowitz; Barry Koplowitz; Howard I. Maibach; Dmitri Lissin (AAPS PharmSciTech, 2021)
Recently, lidocaine topical systems utilizing nonaqueous matrices have been developed and provide efficient lidocaine delivery through the skin, such that lower concentrations of drug provide equivalent or greater drug delivery than drug-in-matrix hydrogel lidocaine patches. This study characterizes drug delivery from a nonaqueous lidocaine topical system with increasing drug load both in vitro and in vivo . Topical systems formulated with either 1.8% or 5.4% lidocaine were applied to healthy volunteers’ backs ( n = 15) for 12 h in a single-center, open-label, four-treatment, four-period crossover pharmacokinetic study. Subjects were dosed with either three 1.8% systems or one, two, or three 5.4% systems in each period. Blood was collected for up to 48 h, and plasma lidocaine levels were measured with a validated HPLC method. In parallel, human and mouse skin models characterized the in vitro skin permeation profile. The pharmacokinetic profile was linear between one, two, and three lidocaine 5.4% applications. Application of three lidocaine 1.8% systems (108 mg lidocaine) was bioequivalent to one lidocaine 5.4% system (108 mg lidocaine). Both topical systems remained well adhered to the skin and irritation was mild. The 5.4% system had approximately threefold higher skin permeability than the 1.8% system in the mouse and human skin models. The results indicate increasing the drug load by three times results in triple the drug delivery both in vivo and in vitro . The relationship between the in vitro permeation and in vivo absorption correlates and is nonlinear.

Eudragit S-100 Surface Engineered Nanostructured Lipid Carriers for Colon Targeting of 5-Fluorouracil: Optimization and In Vitro and In Vivo Characterization - Kruti Borderwala; Sachin Rathod; Sarita Yadav; Bhavin Vyas; Pranav Shah (AAPS PharmSciTech, 2021)

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, 2021)

Targeting Some Enzymes with Repurposing Approved Pharmaceutical Drugs for Expeditious Antiviral Approaches Against Newer Strains of COVID-19 - Swati Sucharita Mohanty; Chita Ranjan Sahoo; Rabindra Nath Padhy (AAPS PharmSciTech, 2021)

Nanoparticles and Nanostructured Films with TGF-β3: Preparation, Characterization, and Efficacy - Ipek Baysal; Goksu Ozcelikay; Samiye Yabanoglu-Ciftci; Bercis Imge Ucar; Ayse Gencer; Betul Arica-Yegin (AAPS PharmSciTech, 2021)

Near-Infrared Hyperspectral Imaging as a Monitoring Tool for On-Demand Manufacturing of Inkjet-Printed Formulations - Sandra Stranzinger; Matthias Wolfgang; Emma Klotz; Otto Scheibelhofer; Patrizia Ghiotti; Johannes G. Khinast; Wen-Kai Hsiao; Amrit Paudel (AAPS PharmSciTech, 2021)
This study evaluates the potential use of near-infrared hyperspectral imaging (NIR-HSI) for quantitative determination of the drug amount in inkjet-printed dosage forms. We chose metformin hydrochloride as a model active pharmaceutical ingredient (API) and printed it onto gelatin films using a piezoelectric inkjet printing system. An industry-ready NIR-HSI sensor combined with a motorized movable linear stage was applied for spectral acquisition. Initial API-substrate screening revealed best printing results for gelatin films with TiO 2 filling. For calibration of the NIR-HSI system, escalating drug doses were printed on the substrate. After spectral pre-treatments, including standard normal variate (SNV) and Savitzky-Golay filtering for noise reduction and enhancement of spectral features, principal component analysis (PCA) and partial least squares (PLS) regression were applied to create predictive models for the quantification of independent printed metformin hydrochloride samples. It could be shown that the concentration distribution maps provided by the developed HSI models were capable of clustering and predicting the drug dose in the formulations. HSI model prediction showed significant better correlation to the reference (HPLC) compared to on-board monitoring of dispensed volume of the printer. Overall, the results emphasize the capability of NIR-HSI as a fast and non-destructive method for the quantification and quality control of the deposited API in drug-printing applications. Graphical abstract

Correction to: Effect of Packaging Materials and the Leached Iron on the Stability of Butorphanol Tartrate Injection - Zijun Dai; Chunmei Zhu; Jinyuan Lyu; Chunfeng Liu; Jiajian Xu; Haoxiang Wu; Fuli Zhang (AAPS PharmSciTech, 2021)

Physicochemical Characterization and Biopharmaceutical Evaluation of ZWF: A Novel Anticancer Drug for the Treatment of Non-small Cell Lung Cancer - Lina Zhao; Li He; Yuan Chen; Tongchao Xia; Le Li; Shengyan Wang; Xu Bao; Junyi Yang (AAPS PharmSciTech, 2021)

Preparation and Characterization of Electrospun Polylactic Acid (PLA) Fiber Loaded with Birch Bark Triterpene Extract for Wound Dressing - Tianyuan Fan; Rolf Daniels (AAPS PharmSciTech, 2021)
Drug-loaded electrospun fibers have attracted increasing attention as a promising wound dressing material due to their capability of preventing from infections and inflammation and maintaining an appropriate environment for wound healing. In this study, polylactic acid (PLA), which is widely used in wound management, was chosen as electrospinnable polymer. A triterpene extract (TE) from the outer bark of birch known for its anti-inflammatory, antiviral, antibacterial, and wound healing effects was chosen to produce TE-loaded PLA electrospun fibers for wound dressing. A binary solvent system of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) was employed, and the ratio of the solvents was optimized for preparing smooth and uniform fibers. The morphology of TE-loaded PLA electrospun fibers was investigated by scanning electron microscopy (SEM). The entrapment of TE in PLA fibers was confirmed by confocal laser scanning microscopy (CLSM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to analyze the solid state of TE in PLA fibers. The release behavior of TE was assayed by a shaking flask method for a period of 96 h. The results revealed that TE-loaded electrospun PLA microfibers could be reliably prepared and are promising future candidates in wound therapy.

Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development - Kefei Wang; Kun Jiang; Xiaoyi Wei; Yulan Li; Tiejie Wang; Yang Song (AAPS PharmSciTech, 2021)

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, 2021)

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, 2021)

Pharmaceutical and Pharmacological Evaluation of the Effect of Nano-Formulated Spironolactone and Progesterone on Inflammation and Hormonal Levels for Managing Hirsutism Experimentally Induced in Rats - Reham I. Amer; Ghada E. Yassin; Reem A. Mohamed; Ahmed M. Fayez (AAPS PharmSciTech, 2021)

Capsanthin, a Plant-Derived Xanthophyll: a Review of Pharmacology and Delivery Strategies - Leenet Edward Kennedy; Annie Abraham; Gunjan Kulkarni; Navya Shettigar; Tanika Dave; Madhur Kulkarni (AAPS PharmSciTech, 2021)

Nebulization of Risedronate Sodium Microspheres for Potential Attenuation of Pulmonary Emphysema: a Promising New Insight of Alveolar Macrophage Apoptosis - Omar A. Elkady; Layla M. Saleh; Mina Ibrahim Tadros; Hanan M. El-laithy (AAPS PharmSciTech, 2021)

Preparation and Characterization of Co-Processed Mannitol and Sorbitol Using NanoCrySP Technology - Srilaxmi G. Rao; Prashantkumar K. Parmar; Katangur Vishruth Reddy; Arvind K. Bansal (AAPS PharmSciTech, 2021)

Solid-in-Oil-in-Water Emulsion: An Innovative Paradigm to Improve Drug Stability and Biological Activity - Anali Sawant; Seema Kamath; Hemanth KG; Girish Pai Kulyadi (AAPS PharmSciTech, 2021)
An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize the thermodynamically unstable emulsion. Various types of emulsions such as water-in-oil (w-o), oil-in-water (o-w), microemulsions, and multiple emulsions are used for delivering certain drugs in the body. Water (aqueous) phase is commonly used for encapsulating proteins and several other drugs in water-in-oil-in-water (w-o-w) emulsion technique. But this method has posed certain problems such as decreased stability, burst release, and low entrapment efficiency. Thus, a novel “solid-in-oil-in-water” (s-o-w) emulsion system was developed for formulating certain drugs, probiotics, proteins, antibodies, and tannins to overcome these issues. In this method, the active ingredient is encapsulated as a solid and added to an oil phase, which formed a solid-oil dispersion. This dispersion was then mixed with water to form a continuous phase for enhancing the drug absorption. This article focuses on the various studies done to investigate the effectiveness of formulations prepared as solid-oil-water emulsions in comparison to conventional water-oil-water emulsions. A summary of the results obtained in each study is presented in this article. The s-o-w emulsion technique may become beneficial in near future as it has shown to improve the stability and efficacy of the entrapped active ingredient. Graphical abstract

Oral Administration of Melatonin or Succinyl Melatonin Niosome Gel Benefits 5-FU-Induced Small Intestinal Mucositis Treatment in Mice - Prangtip Uthaiwat; Aroonsri Priprem; Sirinart Chio-Srichan; Chatri Settasatian; Yao-Chang Lee; Pramote Mahakunakorn; Patcharee Boonsiri; Chanvit Leelayuwat; Patcharaporn Tippayawat; Ploenthip Puthongking; Jureerut Daduang (AAPS PharmSciTech, 2021)

Effect of Chemical Penetration Enhancer-Adhesive Interaction on Drug Release from Transdermal Patch: Mechanism Study Based on FT-IR Spectroscopy, 13C NMR Spectroscopy, and Molecular Simulation - Zheng Luo; Chao Liu; Peng Quan; Yimeng Zhang; Liang Fang (AAPS PharmSciTech, 2021)

Design and Optimization of 3D-Printed Gastroretentive Floating Devices by Central Composite Design - Thapakorn Charoenying; Prasopchai Patrojanasophon; Tanasait Ngawhirunpat; Theerasak Rojanarata; Prasert Akkaramongkolporn; Praneet Opanasopit (AAPS PharmSciTech, 2021)

Experimental Solubility of Ketoconazole, Validation Models, and In vivo Prediction in Human Based on GastroPlus - Afzal Hussain; Mohammad A. Altamimi; Sultan Alshehri; Syed Sarim Imam; Usamah Abdulrahman Alnemer; Md. Wasimul Haque (AAPS PharmSciTech, 2021)

Development of Imatinib Mesylate-Loaded Liposomes for Nose to Brain Delivery: In Vitro and In Vivo Evaluation - Raju Saka; Naveen Chella; Wahid Khan (AAPS PharmSciTech, 2021)

Development of Spray-Dried Cyclodextrin-Based Pediatric Anti-HIV Formulations - Ryan Ivone; Ashvin Fernando; Brenton DeBoef; Samantha A. Meenach; Jie Shen (AAPS PharmSciTech, 2021)

Cationic Polyelectrolyte Nanocapsules of Moxifloxacin for Microbial Keratitis Therapy: Development, Characterization, and Pharmacodynamic Study - Parasuraman Mohan; Karthikeyan Kesavan (AAPS PharmSciTech, 2021)

Influence of Plasdone™ S630 Ultra—an Improved Copovidone on the Processability and Oxidative Degradation of Quetiapine Fumarate Amorphous Solid Dispersions Prepared via Hot-Melt Extrusion Technique - Arun Butreddy; Sandeep Sarabu; Suresh Bandari; Amol Batra; Kamaru Lawal; Nick Ningyi Chen; Vivian Bi; Thomas Durig; Michael A. Repka (AAPS PharmSciTech, 2021)

Formulation and In Vitro Characterization of PLGA/PLGA-PEG Nanoparticles Loaded with Murine Granulocyte-Macrophage Colony-Stimulating Factor - Nicole E. Mihalik; Sijin Wen; Benoit Driesschaert; Timothy D. Eubank (AAPS PharmSciTech, 2021)

Streamlining of the Powder Mixing Process based on a Segregation Test - Simona Römerová; Ondřej Dammer; Petr Zámostný (AAPS PharmSciTech, 2021)

Effect of Elevated pH on the Commercial Enteric-Coated Omeprazole Pellets Resistance: Patent Review and Multisource Generics Comparison - Valentyn Mohylyuk; Anna Yerkhova; Marina Katynska; Vitaliy Sirko; Kavil Patel (AAPS PharmSciTech, 2021)

Process Optimization for the Continuous Production of a Gastroretentive Dosage Form Based on Melt Foaming - Ádám Haimhoffer; Gábor Vasvári; György Trencsényi; Monika Béresová; István Budai; Zsuzsa Czomba; Ágnes Rusznyák; Judit Váradi; Ildikó Bácskay; Zoltán Ujhelyi; Pálma Fehér; Miklós Vecsernyés; et al. (AAPS PharmSciTech, 2021)
Several drugs have poor oral bioavailability due to low or incomplete absorption which is affected by various effects as pH, motility of GI, and enzyme activity. The gastroretentive drug delivery systems are able to deal with these problems by prolonging the gastric residence time, while increasing the therapeutic efficacy of drugs. Previously, we developed a novel technology to foam hot and molten dispersions on atmospheric pressure by a batch-type in-house apparatus. Our aim was to upgrade this technology by a new continuous lab-scale apparatus and confirm that our formulations are gastroretentive. At first, we designed and built the apparatus and continuous production was optimized using a Box–Behnken experimental design. Then, we formulated barium sulfate-loaded samples with the optimal production parameters, which was suitable for in vivo imaging analysis. In vitro study proved the low density, namely 507 mg/cm 3 , and the microCT record showed high porosity with 40 μm average size of bubbles in the molten suspension. The BaSO 4 -loaded samples showed hard structure at room temperature and during the wetting test, the complete wetting was detected after 120 min. During the in vivo study, the X-ray taken showed the retention of the formulation in the rat stomach after 2 h. We can conclude that with our device low-density floating formulations were prepared with prolonged gastric residence time. This study provides a promising platform for marketed active ingredients with low bioavailability.

Effect of Packaging Materials and the Leached Iron on the Stability of Butorphanol Tartrate Injection - Zijun Dai; Chunmei Zhu; Chunfeng Liu; Jinyuan Lyu; Jiajian Xu; Haoxiang Wu; Fuli Zhang (AAPS PharmSciTech, 2021)

Spray-Dried Inhalable Powder Formulations of Therapeutic Proteins and Peptides - Basanth Babu Eedara; Wafaa Alabsi; David Encinas-Basurto; Robin Polt; Heidi M. Mansour (AAPS PharmSciTech, 2021)

Hot-Melt Extrusion: a Roadmap for Product Development - Marta F. Simões; Rui M. A. Pinto; Sérgio Simões (AAPS PharmSciTech, 2021)

Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants - Kristina E. Steffens; Karl G. Wagner (AAPS PharmSciTech, 2021)
The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q 80 : 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q 80 . However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.

Development of Gelucire® 48/16 and TPGS Mixed Micelles and Its Pellet Formulation by Extrusion Spheronization Technique for Dissolution Rate Enhancement of Curcumin - Umesh K. Shinde; Dilipkumar G. Suryawanshi; Purnima D. Amin (AAPS PharmSciTech, 2021)

Predictive Approach to Understand and Eliminate Tablet Breakage During Film Coating - William R. Ketterhagen; Jeffery Larson; Kevin Spence; Jared A. Baird (AAPS PharmSciTech, 2021)

Correction to: Development of Apremilast Solid Dispersion Using TPGS and PVPVA with Enhanced Solubility and Bioavailability - Liuhong Yang; Penghui Wu; Jinchao Xu; Dihuan Xie; Zhongqing Wang; Qian Wang; Yong Chen; Chuan Hua Li; Jiaxin Zhang; Hangping Chen; Guilan Quan (AAPS PharmSciTech, 2021)

Nanocrystals for Improving Oral Bioavailability of Drugs: Intestinal Transport Mechanisms and Influencing Factors - Zonghua Tian; Yaping Mai; Tingting Meng; Shijie Ma; Guojing Gou; Jianhong Yang (AAPS PharmSciTech, 2021)

Design and In Vitro Evaluation of a Slow-Release Intraocular Implant of Betamethasone - Zohreh Sadat Rastegar Ramsheh; Zahra Mohtashami; Neda Kargar; Hamid Akbari Javar; Morteza Rafiee Tehrani; Farid Abedin Dorkoosh (AAPS PharmSciTech, 2021)

Layer-by-Layer Assembled Nanostructured Lipid Carriers for CD-44 Receptor–Based Targeting in HIV-Infected Macrophages for Efficient HIV-1 Inhibition - Ketan Mahajan; Satish Rojekar; Dipen Desai; Smita Kulkarni; Gandhali Bapat; Smita Zinjarde; Pradeep Vavia (AAPS PharmSciTech, 2021)

Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation - Shahla Mirzaeei; Shiva Taghe; Kofi Asare-Addo; Ali Nokhodchi (AAPS PharmSciTech, 2021)
A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus , respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli . In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC 0–96 for the nanofibers was 9–20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

Preparation and Characterization of a Lutein Solid Dispersion to Improve Its Solubility and Stability - Chaemin Lim; Jin Kook Kang; Chan Eun Jung; Taehoon Sim; Jaewon Her; Kioh Kang; Eun Seong Lee; Yu Seok Youn; Han-Gon Choi; Kyung Taek Oh (AAPS PharmSciTech, 2021)

From Lab Formulation Development to CTM Manufacturing of KO-947 Injectable Drug Products: a Case Study and Lessons Learned - Xiaohu Deng; Pingda Ren; Wanping Mai; Yi Wang; Yuanyang Zhang; Hongbing Wu; Yinwei Xie; Huazhen Chen (AAPS PharmSciTech, 2021)

Evaluation of Microwave-Assisted Extraction Method for Preparation and Assessment of Thai Herbal Medicine Oral Tablets With Enriched Phytochemical Compounds - Patcharawalai Jaisamut; Subhaphorn Wanna; Atcharaporn Thanakoon; Supanit Saejew; Nutkawan Saowapark; Waramporn Suchato; Preyanuch Chumvong; Tanpisit Kosawiwat; Phonsinee Momaklua; Sasitorn Chusri (AAPS PharmSciTech, 2021)

Correction to: Coating Lacticaseibacillus rhamnosus GG in Alginate Systems: an Emerging Strategy Towards Improved Viability in Orange Juice - Angela Bonaccorso; Nunziatina Russo; Alessia Romeo; Claudia Carbone; Maria Aurora Grimaudo; Carmen Alvarez-Lorenzo; Cinzia Randazzo; Teresa Musumeci; Cinzia Caggia (AAPS PharmSciTech, 2021)

Novel Gellan Gum-Based In Situ Nanovesicle Formulation of Docetaxel for Its Localized Delivery Using Depot Formation - Amrinder Singh; Shubham Thakur; Narpinder Singh; Satwinderjeet Kaur; Subheet Kumar Jain (AAPS PharmSciTech, 2021)

Recent Advancement in Topical Nanocarriers for the Treatment of Psoriasis - Prativa Biswasroy; Deepak Pradhan; Biswakanth Kar; Goutam Ghosh; Goutam Rath (AAPS PharmSciTech, 2021)

Ocular Distribution of Papaverine Using Non-aqueous Vehicles - Priyanka Agarwal; Sairam Behera; Ilva Dana Rupenthal (AAPS PharmSciTech, 2021)

Formulation, Evaluation, and Clinical Assessment of Novel Solid Lipid Microparticles of Tetracycline Hydrochloride for the Treatment of Periodontitis - Rajkiran Narkhede; Rajani Athawale; Nikita Patil; MalaDixit Baburaj (AAPS PharmSciTech, 2021)

Nanoemulgel for Improved Topical Delivery of Desonide: Formulation Design and Characterization - Qiuyan Ma; Jing Zhang; Bohong Lu; Huaqing Lin; Rajib Sarkar; Tao Wu; Xuee Li (AAPS PharmSciTech, 2021)

Lipid Coating of Chitosan Nanogels for Improved Colloidal Stability and In Vitro Biocompatibility - Victor Passos Gibson; Julia Balestrero Braga Nunes; Deborah Quintanilha Falcao; V. Gaëlle Roullin; Jeanne Leblond Chain (AAPS PharmSciTech, 2021)

Triphenylphosphonium functionalized Ficus religiosa L. extract loaded nanoparticles improve the mitochondrial function in oxidative stress induced diabetes - Priyanka Karunanidhi; Nitin Verma; Dulla Naveen Kumar; Ashish Kumar Agrawal; Sanjay Singh (AAPS PharmSciTech, 2021)

[10]-Gingerol-Loaded Nanoemulsion and its Biological Effects on Triple-Negative Breast Cancer Cells - Ideli Zanesco-Fontes; Ana Carolina Lopes Silva; Patrícia Bento da Silva; Jonatas Lobato Duarte; Leonardo Delello Di Filippo; Marlus Chorilli; Marcia Regina Cominetti; Ana Carolina Baptista Moreno Martin (AAPS PharmSciTech, 2021)

Combination of Phospholipid Complex and Matrix Dispersion - Ravi Kumar Chakravarti; Shamandeep Kaur; Sanjaya K. Samal; Mahesh C. Kashyap; Abhay T. Sangamwar (AAPS PharmSciTech, 2021)

Fabrication and Evaluation of Celecoxib Oral Oleogel to Reduce the Inflammation of Ulcerative Colitis - Nermin M. Sheta; Sylvia A. Boshra (AAPS PharmSciTech, 2021)

RETRACTED ARTICLE: Bi-polymeric Spongy Matrices Through Cross-linking Polymerization: Synthesized and Evaluated for Solubility Enhancement of Acyclovir - Saima Asghar; Naveed Akhtar; Muhammad Usman Minhas; Kifayat Ullah Khan (AAPS PharmSciTech, 2021)

RETRACTED ARTICLE: Fluvastatin-Loaded Emulsomes Exhibit Improved Cytotoxic and Apoptosis in Prostate Cancer Cells - Nabil A. Alhakamy; Shaimaa M. Badr-Eldin; Hibah M. Aldawsari; Anas Alfarsi; Thikryat Neamatallah; Solomon Z. Okbazghi; Usama A. Fahmy; Osama A.A. Ahmad; Basma G. Eid; Wael Ali Mahdi; Adel F. Alghaith; Sultan Alshehri; et al. (AAPS PharmSciTech, 2021)

Formulation Approach that Enables the Coating of a Stable Influenza Vaccine on a Transdermal Microneedle Patch - Mahmoud Ameri; Yi Ao; Hayley Lewis (AAPS PharmSciTech, 2021)

Middle East Respiratory Syndrome (MERS) Virus—Pathophysiological Axis and the Current Treatment Strategies - Abdullah M Alnuqaydan; Abdulmajeed G Almutary; Arulmalar Sukamaran; Brian Tay Wei Yang; Xiao Ting Lee; Wei Xuan Lim; Yee Min Ng; Rania Ibrahim; Thiviya Darmarajan; Satheeshkumar Nanjappan; Jestin Chellian; Mayuren Candasamy; et al. (AAPS PharmSciTech, 2021)

Tozinameran (BNT162b2) Vaccine: The Journey from Preclinical Research to Clinical Trials and Authorization - Nimrat Khehra; Inderbir Padda; Urooj Jaferi; Harshan Atwal; Shreya Narain; Mayur S. Parmar (AAPS PharmSciTech, 2021)

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, 2021)

Insights on the Critical Parameters Affecting the Probiotic Viability During Stabilization Process and Formulation Development - Sharda Gurram; Durgesh K. Jha; Devanshi S. Shah; Madhuri M. Kshirsagar; Purnima D. Amin (AAPS PharmSciTech, 2021)

Critical Tools in Tableting Research: Using Compaction Simulator and Quality by Design (QbD) to Evaluate Lubricants’ Effect in Direct Compressible Formulation - Nailla Jiwa; Yildiz Ozalp; Gizem Yegen; Buket Aksu (AAPS PharmSciTech, 2021)

Intranasal In Situ Gel of Apixaban-Loaded Nanoethosomes: Preparation, Optimization, and In Vivo Evaluation - Ahmed A. El-Shenawy; Reda A. Mahmoud; Essam A. Mahmoud; Mohamed S. Mohamed (AAPS PharmSciTech, 2021)

Application of Design of Experiments® Approach-Driven Artificial Intelligence and Machine Learning for Systematic Optimization of Reverse Phase High Performance Liquid Chromatography Method to Analyze Simultaneously Two Drugs (Cyclosporin A and Etodolac) in Solution, Human Plasma, Nanocapsules, and Emulsions - Syed Nazrin Ruhina Rahman; Oly Katari; Datta Maroti Pawde; Gopi Sumanth Bhaskar Boddeda; Abhinab Goswami; Srinivasa Rao Mutheneni; Tamilvanan Shunmugaperumal (AAPS PharmSciTech, 2021)

The Effect of Process Variables and Binder Concentration on Tabletability of Metformin Hydrochloride and Acetaminophen Granules Produced by Twin Screw Melt Granulation with Different Polymeric Binders - Amol Batra; Atsawin Thongsukmak; Dipen Desai; Abu T. M. Serajuddin (AAPS PharmSciTech, 2021)

Use of a Design of Experiments (DoE) Approach to Optimize Large-Scale Freeze-Thaw Process of Biologics - Bruna Minatovicz; Robin Bogner; Bodhisattwa Chaudhuri (AAPS PharmSciTech, 2021)

National Institute for Pharmaceutical Technology & Education (NIPTE) Research and Perspective: Advances in Nanotechnology-Based Drug Delivery - Aliasger K. Salem; Xiuling Lu (AAPS PharmSciTech, 2021)

Impact of Different Mixing Methods on the Performance of Suspension-Based Transdermal Delivery Systems - Sonalika Arup Bhattaccharjee; Madhura Kale; Ngan Le; Ajay K. Banga (AAPS PharmSciTech, 2021)

Formulation and Characterization of Microcapsules Encapsulating PC12 Cells as a Prospective Treatment Approach for Parkinson’s Disease - Devyani J. Joshi; Neha M. Chitre; Amit Bansal; Kevin S. Murnane; Martin J. D’Souza (AAPS PharmSciTech, 2021)

Scale-up of Fluid Bed Granulation Using a Scale-Independent Parameter and a Process Model - Emmanuela Gavi; Angela Dischinger (AAPS PharmSciTech, 2021)

Formulation, Pharmacokinetics evaluation, and IVIVC Assessment of Gliclazide Multiparticulates in Rat Model - Ahmed A. El-Ashmawy; Aya R. Abdou; Nesrin F. Taha; Ebtesam W. Elsayed; Khaled M. Mahmoud; Laila H. Emara (AAPS PharmSciTech, 2021)

Correction to: Transdermal Permeation of Caffeine Aided by Ionic Liquids: Potential for Enhanced Treatment of Cellulites - Audrey N. Hernandes; Rodrigo Boscariol; Victor M. Balcão; Marta M. D. C. Vila (AAPS PharmSciTech, 2021)

Cycle Development in a Mini-Freeze Dryer: Evaluation of Manometric Temperature Measurement in Small-Scale Equipment - Tim Wenzel; Margit Gieseler; Ahmad M. Abdul-Fattah; Henning Gieseler (AAPS PharmSciTech, 2021)
The objective of this research was to assess the applicability of manometric temperature measurement (MTM) and SMART™ for cycle development and monitoring of critical product and process parameters in a mini-freeze dryer using a small set of seven vials. Freeze drying cycles were developed using SMART™ which automatically defines and adapts process parameters based on input data and MTM feedback information. The freeze drying behavior and product characteristics of an amorphous model system were studied at varying wall temperature control settings of the cylindrical wall surrounding the shelf in the mini-freeze dryer. Calculated product temperature profiles were similar for all different wall temperature settings during the MTM-SMART™ runs and in good agreement with the temperatures measured by thermocouples. Product resistance profiles showed uniformity in all of the runs conducted in the mini-freeze dryer, but absolute values were slightly lower compared to values determined by MTM in a LyoStar™ pilot-scale freeze dryer. The resulting cakes exhibited comparable residual moisture content and optical appearance to the products obtained in the larger freeze dryer. An increase in intra-vial heterogeneity was found for the pore morphology in the cycle with deactivated wall temperature control in the mini-freeze dryer. SMART™ cycle design and product attributes were reproducible and a minimum load of seven 10R vials was identified for more accurate MTM values. MTM-SMART™ runs suggested, that in case of the wall temperature following the product temperature of the center vial, product temperatures differ only slightly from those in the LyoStar™ freeze dryer.

Development and Validation of a Discriminatory Dissolution Model for an Immediately Release Dosage Form by DOE and Statistical Approaches - Mingkun Fu; Ellen Conroy; Michael Byers; Lakshminarasimhan Pranatharthiharan; Thierry Bilbault (AAPS PharmSciTech, 2021)

Comparative taste-masking evaluation of microencapsulated bitter drugs using Smartseal 30D and ReadyMix for paediatric dosage forms - Leona Chidinma Muoka; Steven A. Ross; Md Sadeque Hossain Mithu; Uttom Nandi; Dennis Douroumis (AAPS PharmSciTech, 2021)

Probing Dynamic Behavior of Chemical Enhancers Passing In and Out of the Stratum Corneum and Modulation by Biodegradable Enhancer - Lijuan Zeng; Guangqiang Yang; Jianping Liu; Danyi Quan; Wenting Song (AAPS PharmSciTech, 2021)

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, 2021)

Performance of Low Air Volume Dry Powder Inhalers (LV-DPI) when Aerosolizing Excipient Enhanced Growth (EEG) Surfactant Powder Formulations - Susan Boc; Mohammad A. M. Momin; Dale R. Farkas; Worth Longest; Michael Hindle (AAPS PharmSciTech, 2021)

Borneol: a Promising Monoterpenoid in Enhancing Drug Delivery Across Various Physiological Barriers - Madhur Kulkarni; Niserga Sawant; Anjali Kolapkar; Aishwarya Huprikar; Namita Desai (AAPS PharmSciTech, 2021)

Development of Apremilast Solid Dispersion Using TPGS and PVPVA with Enhanced Solubility and Bioavailability - Liuhong Yang; Penghui Wu; Jinchao Xu; Dihuan Xie; Zhongqing Wang; Qian Wang; Yong Chen; Chuan Hua Li; Jiaxin Zhang; Hangping Chen; Guilan Quan (AAPS PharmSciTech, 2021)

Tumor-Targeted Delivery of Bufalin-Loaded Modified Albumin–Polymer Hybrid for Enhanced Antitumor Therapy and Attenuated Hemolysis Toxicity and Cardiotoxicity - Ying Xu; Lei Tang; Peng Chen; Mei Chen; Miaomiao Zheng; Feng Shi; Yanchun Wang (AAPS PharmSciTech, 2021)

Development and Characterization of Excipient Enhanced Growth (EEG) Surfactant Powder Formulations for Treating Neonatal Respiratory Distress Syndrome - Susan Boc; Mohammad A. M. Momin; Dale R. Farkas; Worth Longest; Michael Hindle (AAPS PharmSciTech, 2021)

Improving Oral Bioavailability of Luteolin Nanocrystals by Surface Modification of Sodium Dodecyl Sulfate - Jiali Liu; Yongbing Sun; Meng Cheng; Qiaoming Liu; Wan Liu; Chao Gao; Jianfang Feng; Yi Jin; Liangxing Tu (AAPS PharmSciTech, 2021)

Correction to: Effect of Surface Property on the Release and Oral Absorption of Solid Sirolimus-Containing Self-Microemulsifying Drug Delivery System - Xueting Zhang; Zhenzhen Chen; Chun Tao; Jing Zhang; Minxin Zhang; Jialiang Zhang; Zhihong Liu; Jiao Lin; Hang Xu; Qian Zhang; Hongtao Song (AAPS PharmSciTech, 2021)

Development of an In Vivo Predictive Dissolution Methodology of Topiroxostat Immediate-Release Tablet Using In Silico Simulation - Gang Li; Haiyang Yang; Wei Liu; Chen Shen; Yanhua Ji; Yilu Sun; Qing Huo; Yang Liu; Guopeng Wang (AAPS PharmSciTech, 2021)

Preparation of High-Drug-Loaded Clarithromycin Gastric-Floating Sustained-Release Tablets Using 3D Printing - Peihong Chen; Haosen Luo; Siyu Huang; Jinling Liu; Minmei Lin; Fan Yang; Junfeng Ban; Zeju Huang; Zhufen Lu; Qingchun Xie; YanZhong Chen (AAPS PharmSciTech, 2021)

Printing Methods in the Production of Orodispersible Films - Maram Suresh Gupta; Tegginamath Pramod Kumar; Robert Davidson; Guruprasad Rao Kuppu; Kamla Pathak; Devegowda Vishakante Gowda (AAPS PharmSciTech, 2021)

Next-Generation COVID-19 Vaccines Should Take Efficiency of Distribution into Consideration - Khaled AboulFotouh; Zhengrong Cui; Robert O. Williams (AAPS PharmSciTech, 2021)

Analytical Method Lifecycle Management in Pharmaceutical Industry: a Review - Lúcia Volta e Sousa; Ricardo Gonçalves; José C. Menezes; António Ramos (AAPS PharmSciTech, 2021)

Enhanced Solubility and Bioavailability of Dolutegravir by Solid Dispersion Method: In Vitro and In Vivo Evaluation—a Potential Approach for HIV Therapy - Sunita Chaudhary; Anroop B. Nair; Jigar Shah; Bapi Gorain; Shery Jacob; Hiral Shah; Vimal Patel (AAPS PharmSciTech, 2021)

Doxorubicin-Loaded Mixed Micelles for the Effective Management of Skin Carcinoma: In Vivo Anti-Tumor Activity and Biodistribution Studies - Nagarani Thotakura; Anshul Panjeta; Poonam Negi; Simran Preet; Kaisar Raza (AAPS PharmSciTech, 2021)

Development and Evaluation of Topical Delivery of Microemulsions Containing Adapalene (MEs-Ap) for Acne - Bing Shao; Lixin Sun; Na Xu; Hongwei Gu; Hongyu Ji; Linhua Wu (AAPS PharmSciTech, 2021)

Correction to: A New Approach for Dry Eye Management by Mucoadhesive In situ Gel of Vitamin B12: Formulation, In vitro and In vivo Assessment - Soad A. Mohamad; Eman Alaaeldin; Raafat M. A. Abdallah; Heba F. Mansour (AAPS PharmSciTech, 2021)

Coating Lacticaseibacillus rhamnosus GG in Alginate Systems: an Emerging Strategy Towards Improved Viability in Orange Juice - Angela Bonaccorso; Nunziatina Russo; Alessia Romeo; Claudia Carbone; Maria Aurora Grimaudo; Carmen Alvarez-Lorenzo; Cinzia Randazzo; Teresa Musumeci; Cinzia Caggia (AAPS PharmSciTech, 2021)
Fruit juices are successfully proposed as suitable probiotic vehicles, but researchers’ efforts should be developed to avoid effects of bacteria overgrowing on sensory and nutritional cues of final products and to preserve viability of probiotic bacteria during storage. In the present study, encapsulation of Lacticaseibacillus rhamnosus GG strain in alginate systems was performed through ionotropic gelation technology. The alginate systems were optimized by using Box-Behnken Design to investigate the influence of three independent variables at three different levels: particle mean size and polydispersity index. The optimized probiotic-loaded alginate particles were added to orange juice samples. The viability of the probiotic strain, both as free and microencapsulated, was evaluated in orange juice stored at 5°C for 35 days. Morphology and size of probiotic-loaded alginate particles were found suitable for incorporation into juice. TEM analysis revealed that unloaded systems were clustered as nanoparticles (CL_NP), while the loaded sample appeared as a coated system (Coated_LGG). Microbiological evaluation revealed that the encapsulation assured the survival of Coated_LGG, with a reduction of less than 1-unit log in cellular density after 35 days of refrigerated storage in orange juice. Results indicated that the encapsulated bacteria did not affect the macroscopic properties neither the microbiological characteristic of orange juice; thus, it can be proposed as functional food.

Coating characterization by hyperspectroscopy and predictive dissolution models of tablets coated with blends of cellulose acetate and cellulose acetate phthalate - Tahir Khuroo; Eman M. Mohamed; Sathish Dharani; Hamideh Afrooz; Sogra F. Barakh Ali; Phillip Cook; Mansoor A. Khan; Ziyaur Rahman (AAPS PharmSciTech, 2021)

Transdermal Permeation of Caffeine Aided by Ionic Liquids: Potential for Enhanced Treatment of Cellulite - Audrey N. Hernandes; Rodrigo Boscariol; Victor M. Balcão; Marta M. D. C. Vila (AAPS PharmSciTech, 2021)

A CFD Digital Twin to Understand Miscible Fluid Blending - John Thomas; Kushal Sinha; Gayathri Shivkumar; Lei Cao; Marina Funck; Sherwin Shang; Nandkishor K. Nere (AAPS PharmSciTech, 2021)

Development and Characterization of Saturated Fatty Acid-Engineered, Silica-Coated Lipid Vesicular System for Effective Oral Delivery of Alfa-Choriogonadotropin - Viral Shah; Amee Jobanputra; Bhagawati Saxena; Manish Nivsarkar (AAPS PharmSciTech, 2021)

Muscle Tissue as a Surrogate for In Vitro Drug Release Testing of Parenteral Depot Microspheres - Jan Kozak; Miloslava Rabiskova; Alf Lamprecht (AAPS PharmSciTech, 2021)
Despite the importance of drug release testing of parenteral depot formulations, the current in vitro methods still require ameliorations in biorelevance. We have investigated here the use of muscle tissue components to better mimic the intramuscular administration. For convenient handling, muscle tissue was used in form of a freeze-dried powder, and a reproducible process of incorporation of tested microspheres to an assembly of muscle tissue of standardized dimensions was successfully developed. Microspheres were prepared from various grades of poly(lactic-co-glycolic acid) (PLGA) or ethyl cellulose, entrapping flurbiprofen, lidocaine, or risperidone. The deposition of microspheres in the muscle tissue or addition of only isolated lipids into the medium accelerated the release rate of all model drugs from microspheres prepared from ester-terminated PLGA grades and ethyl cellulose, however, not from the acid-terminated PLGA grades. The addition of lipids into the release medium increased the solubility of all model drugs; nonetheless, also interactions of the lipids with the polymer matrix (ad- and absorption) might be responsible for the faster drug release. As the in vivo drug release from implants is also often faster than in simple buffers in vitro , these findings suggest that interactions with the tissue lipids may play an important role in these still unexplained observations.

Subcutaneous Delivery of Albumin: Impact of Thermosensitive Hydrogels - Nidhi Patel; Nan Ji; Yingzhe Wang; Xingcong Li; Nigel Langley; Chalet Tan (AAPS PharmSciTech, 2021)

A Data-Mining Approach for the Quantitative Assessment of Physicochemical Properties of Molecular Compounds in the Skin Flux - Hoo-kyun Choi; Gayathri Acharya; Yugyung Lee; Chi H. Lee (AAPS PharmSciTech, 2021)

Experimental Solubility, Thermodynamic/Computational Validations, and GastroPlus-Based In Silico Prediction for Subcutaneous Delivery of Rifampicin - Wael A. Mahdi; Afzal Hussain; Mohammad A. Altamimi; Sultan Alshehri; Sarah I. Bukhari; Mohd Neyaz Ahsan (AAPS PharmSciTech, 2021)

99mTc Stearyl 6-(benzylidenehydrazinyl) nicotinamide Liposomes as Tumor Permeability Evaluation Tracer - Mirel Cabrera; Nicole Lecot; Marcelo Fernández; J. P. Gambini; Williams Porcal; Pablo Cabral (AAPS PharmSciTech, 2021)

Nanoparticulate tablet dosage form of lisofylline-linoleic acid conjugate for type 1 diabetes: in situ single-pass intestinal perfusion (SPIP) studies and pharmacokinetics in rat - Kishan S. Italiya; Arihant K. Singh; Deepak Chitkara; Anupama Mittal (AAPS PharmSciTech, 2021)

Development of Nanonized Nitrendipine and Its Transformation into Nanoparticulate Oral Fast Dissolving Drug Delivery System - Neha Vishal Gandhi; Uday Arvind Deokate; Sachidanand Shankar Angadi (AAPS PharmSciTech, 2021)

Preparation and Evaluation of Co-amorphous Formulations of Telmisartan—Amino Acids as a Potential Method for Solubility and Dissolution Enhancement - Mai Khanfar; Mayyas Al-Remawi; Faisal Al-Akayleh; Suha Hmouze (AAPS PharmSciTech, 2021)

Self-Assembled Micelles Improve the Oral Bioavailability of Dihydromyricetin and Anti-Acute Alcoholism Activity - Jing Ye; Sha Bao; Shiying Zhao; Yujing Zhu; Qiao Ren; Rui Li; Xiaohong Xu; Quan Zhang (AAPS PharmSciTech, 2021)

Preparation of Fraxetin Long Circulating Liposome and Its Anti-enteritis Effect - Zhiwei Miao; Lei Zhang; Mingjia Gu; Jianyi Huang; Xiaoyu Wang; Jing Yan; Yan Xu; Libing Wang (AAPS PharmSciTech, 2021)

Effect of Surface Property on the Release and Oral Absorption of Solid Sirolimus-Containing Self-microemulsifying Drug Delivery System - Xueting Zhang; Zhenzhen Chen; Chun Tao; Jing Zhang; Minxin Zhang; Jialiang Zhang; Zhihong Liu; Jiao Lin; Hang Xu; Qian Zhang; Hongtao Song (AAPS PharmSciTech, 2021)

Review of Approaches for Increasing Ophthalmic Bioavailability for Eye Drop Formulations - Olivia L. Lanier; Miranda G. Manfre; Claire Bailey; Zhen Liu; Zachary Sparks; Sandesh Kulkarni; Anuj Chauhan (AAPS PharmSciTech, 2021)

Repurposing Melt Degradation for the Evaluation of Mixed Amorphous-Crystalline Blends - Sumayah Abdul-jabbar; Daniel W. Wong; Gary P. Martin; Brendon Woodhead; Paul G. Royall (AAPS PharmSciTech, 2021)
Medicine regulators require the melting points for crystalline drugs, as they are a test for chemical and physical quality. Many drugs, especially salt-forms, suffer concomitant degradation during melting; thus, it would be useful to know if the endotherm associated with melt degradation may be used for characterising the crystallinity of a powder blend. Therefore, the aim of this study was to investigate whether melt-degradation transitions can detect amorphous content in a blend of crystalline and amorphous salbutamol sulphate. Salbutamol sulphate was rendered amorphous by freeze and spray-drying and blended with crystalline drug, forming standards with a range of amorphous content. Crystalline salbutamol sulphate was observed to have a melt-degradation onset of 198.2±0.2°C, while anhydrous amorphous salbutamol sulphate prepared by either method showed similar glass transition temperatures of 119.4±0.7°C combined. Without the energy barrier provided by the ordered crystal lattice, the degradation endotherm for amorphous salbutamol sulphate occurred 50°C below the melting point, with an onset of 143.6±0.2°C. The enthalpies for this degradation transition showed no significant difference between freeze- and spray-dried samples ( p >0.05). Distinct from convention, partial integration of the crystalline melt-degradation endotherm was applied to the region 193–221°C which had no contribution from the degradation of amorphous salbutamol sulphate. The linear correlation of these partial areas with amorphous content, R 2 =0.994, yielded limits of detection and quantification of 0.13% and 0.44% respectively, independent of drying technique. Melt-degradation transitions may be re-purposed for the measurement of amorphous content in powder blends, and they have potential for evaluating disorder more generally.

Levobupivacaine-Loaded Liposome Associated with Thermogel for Prolonged Analgesia - Ana Rosa Brissant de Andrade; Rafaela de Siqueira Ferraz-Carvalho; Victor Passos Gibson; Juliana Kishishita; Mariane Cajuba de Britto Lira Nogueira; Nereide Stela Santos-Magalhães; Leila Bastos Leal; Davi Pereira de Santana (AAPS PharmSciTech, 2021)

Preparation and In Vivo Evaluation of Rosmarinic Acid-Loaded Transethosomes After Percutaneous Application on a Psoriasis Animal Model - Azahara Rodríguez-Luna; Elena Talero; Javier Ávila-Román; Ana María Fernández Romero; Antonio M. Rabasco; Virginia Motilva; María Luisa González-Rodríguez (AAPS PharmSciTech, 2021)

Formulation of Medicated Chewing Gum Containing Sceletium tortuosum and Process Optimization Utilizing the SeDeM Diagram Expert System - Joe M. Viljoen; Sonja van der Walt; Josias H. Hamman (AAPS PharmSciTech, 2021)

Nanoparticle-Based Delivery to Treat Spinal Cord Injury—a Mini-review - Atanu Chakraborty; Andrew J. Ciciriello; Courtney M. Dumont; Ryan M. Pearson (AAPS PharmSciTech, 2021)

Container Closure and Delivery Considerations for Intravitreal Drug Administration - Ashwin C. Parenky; Saurabh Wadhwa; Hunter H. Chen; Amardeep S. Bhalla; Kenneth S. Graham; Mohammed Shameem (AAPS PharmSciTech, 2021)
Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 μL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.

Investigating the Influence of Tablet Location Inside Dissolution Test Apparatus on Polymer Erosion and Drug Release of a Surface-Erodible Sustained-Release Tablet Using Computational Simulation Methods - Hao Lou; Michael J. Hageman (AAPS PharmSciTech, 2021)

Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations - Mohammad A. Azad; Gerard Capellades; Allison B. Wang; David M. Klee; Gregory Hammersmith; Kersten Rapp; David Brancazio; Allan S. Myerson (AAPS PharmSciTech, 2021)
The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder. Graphical Abstract

A Multi-variate Mathematical Model for Simulating the Granule Size Distribution in Roller Compaction-Milling Process - Hossein Amini; Ilgaz Akseli (AAPS PharmSciTech, 2021)

Galactose-Modified PH-Sensitive Niosomes for Controlled Release and Hepatocellular Carcinoma Target Delivery of Tanshinone IIA - Xixi Hu; Jun Zhang; Lulu Deng; Hao Hu; Junjie Hu; Guohua Zheng (AAPS PharmSciTech, 2021)
Increasing the drug tumor-specific accumulation and controlling their release is considered one of the most effective ways to increase the efficacy of drugs. Here, we developed a vesicle system that can target hepatoma and release drugs rapidly within tumor cells. This non-ionic surfactant vesicle is biodegradable. Galactosylated stearate has been used to glycosylate the vesicles to achieve liver targeting; replacement of a portion (Chol:CHEMS = 1:1) of cholesterol by cholesteryl hemisuccinate (CHEMS) allows for a rapid release of drugs in an acidic environment. In vitro release experiments confirmed that galactose-modified pH-sensitive niosomes loaded with tanshinone IIA had excellent drug release performance in acid medium. In vitro experiments using ovarian cancer cells (A2780), colon cancer cells (HCT8), and hepatoma cell (Huh7, HepG2) confirmed that the preparation had specific targeting ability to hepatoma cells compared with free drugs, and this ability was dependent on the galactose content. Furthermore, the preparation also had a more substantial inhibitory effect on tumor cells, and subsequent apoptosis assays and cell cycle analyses further confirmed its enhanced anti-tumor effect. Results of pharmacokinetic experiments confirmed that the vesicle system could significantly extend the blood circulation time of tanshinone IIA, and the larger area under the curve indicated that the preparation had a better drug effect. Thus, the results of biodistribution experiments confirmed the in vivo liver targeting ability of this preparation. Niosomes designed in this manner are expected to be a safe and effective drug delivery system for liver cancer therapy.

Chemotherapeutic Agent-Induced Vulvodynia, an Experimental Model - Srinath Rangappa; Vijay Kumar Shankar; Seongbong Jo; Michael A. Repka; S. Narasimha Murthy (AAPS PharmSciTech, 2021)

Egg White Protein Carrier-Assisted Development of Solid Dispersion for Improved Aqueous Solubility and Permeability of Poorly Water Soluble Hydrochlorothiazide - Darshan R. Telange; Shirish P. Jain; Anil M. Pethe; Prashant S. Kharkar (AAPS PharmSciTech, 2021)

Synthetic Receptor-Based Targeting Strategies to Improve Tumor Drug Delivery - Susheel Kumar Nethi; Shubhmita Bhatnagar; Swayam Prabha (AAPS PharmSciTech, 2021)

Development and Characterization of Venetoclax Nanocrystals for Oral Bioavailability Enhancement - Shabari Girinath Kala; Santhivardhan Chinni (AAPS PharmSciTech, 2021)

Stabilization and X-ray Attenuation of PEGylated Cholesterol/Polycaprolactone-Based Perfluorooctyl Bromide Nanocapsules for CT Imaging - André O’Reilly Beringhs; Dennis Ndaya; Reuben Bosire; Rajeswari M. Kasi; Xiuling Lu (AAPS PharmSciTech, 2021)

Influence of Dose on Neutrophil-Mediated Delivery of Nanoparticles for Tumor-Targeting Therapy Strategies - Min Liu; Cong Li; NaYan; Dan Zhao; Hongxia Zhang; Jie Li; Xueying Tang; Xinrong Liu; Yihui Deng; Yanzhi Song (AAPS PharmSciTech, 2021)

Pharmaceutical Quality, Team Science, and Education Themes: Observations and Commentary on a Remarkable AAPS PharmSciTech Theme Issue - Ajaz S. Hussain; Kenneth Morris; Vadim J. Gurvich (AAPS PharmSciTech, 2021)

A New Approach for Dry Eye Management By Mucoadhesive In situ Gel of Vitamin B12: Formulation, In vitro and In vivo Assessment - Soad A. Mohamad; Eman Alaaeldin; Raafat M. A. Abdallah; Heba F. Mansour (AAPS PharmSciTech, 2021)

Applications of the Linear Mass-Sectional Breakage Population Balance to Various Milling Process Configurations - Russell B. Diemer (AAPS PharmSciTech, 2021)

Evaluating Solubility of Celecoxib in Age-Appropriate Fasted- and Fed-State Gastric and Intestinal Biorelevant Media Representative of Adult and Pediatric Patients: Implications on Future Pediatric Biopharmaceutical Classification System - Ramzi Shawahna; Ahed Zyoud; Aseel Haj-Yahia; Raheek Taya (AAPS PharmSciTech, 2021)

Liqui-Tablet: the Innovative Oral Dosage Form Using the Newly Developed Liqui-Mass Technology - Matthew Lam; Kofi Asare-Addo; Ali Nokhodchi (AAPS PharmSciTech, 2021)
In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile.

Evaluation of Packaging Materials in Freeze-Drying: Use of Polymer Caps and Nested Vials and Their Impact on Process and Product Attributes - Tim Wenzel; Henning Gieseler (AAPS PharmSciTech, 2021)
Current trends in the pharmaceutical industry led to a demand for more flexible manufacturing processes with smaller batch sizes. Prepackaged nested vials that can be processed as a unit were introduced into the market to fulfill this need. However, vial nests provide a different thermal environment for the vials compared to a hexagonal packaging array and could therefore influence product temperature profiles, primary drying times, and product quality attributes. Polymer caps with the possibility of vial closure inside the freeze-drying chamber were developed to remove the risks and need of a crimping process. A general concern with the use of such caps is the possibility of an increase in resistance to water vapor flow out of the vial. This case study investigated the effect of the LyoSeal ® and PLASCAP ® polymer caps and EZ-fill ® nests on the freeze-drying process. Amorphous and partially crystalline model formulations were freeze-dried. Process data and product quality attributes were compared for regularly stoppered vials and vials with polymer caps as well as vials in a hexagonal packaging array and nested vials. The results indicated no increased resistance or impeded water vapor flow by the polymer caps. Differences in the macro- and microscopic appearances of products and a trend towards lower product temperatures were observed for the investigated nest type compared to a regular hexagonal packaging array. Consequently, the polymer caps could be used as an alternative to regular stoppers without affecting freeze-drying process data or product quality attributes, while the different thermal environment of nested vials should be considered.

Correction to: Pluronic-Coated Biogenic Gold Nanoparticles for Colon Delivery of 5-Fluorouracil: In vitro and Ex vivo Studies - Wael A. Mahdi; Afzal Hussain; Mohd Ramzan; Abdul Faruk; Sarah I. Bukhari; Abhimanyu Dev (AAPS PharmSciTech, 2021)

A One-Step Twin-Screw Melt Granulation with Gelucire 48/16 and Surface Adsorbent to Improve the Solubility of Poorly Soluble Drugs: Effect of Formulation Variables on Dissolution and Stability - Sandeep Sarabu; Venkata Raman Kallakunta; Arun Butreddy; Karthik Yadav Janga; Srinivas Ajjarapu; Suresh Bandari; Feng Zhang; S. Narasimha Murthy; Michael A. Repka (AAPS PharmSciTech, 2021)

An Analysis for Adulteration and Contamination of Over-the-Counter Weight-Loss Products - Ping Hung Boris Wong; Joanna E. Harnett; David Clases; Nial J. Wheate (AAPS PharmSciTech, 2021)

Tailored Doxycycline Hyclate Loaded In Situ Gel for the Treatment of Periodontitis: Optimization, In Vitro Characterization, and Antimicrobial Studies - Ketan M. Ranch; Furqan A. Maulvi; Akshay R. Koli; Ditixa T. Desai; Rajesh K. Parikh; Dinesh O. Shah (AAPS PharmSciTech, 2021)

Comparative Analysis of Collagen and Chitosan-based Dressing for Haemostatic and Wound Healing Application - Divya Tripathi; Kartikey Rastogi; Priyanka Tyagi; Harish Rawat; Gaurav Mittal; Abhinav Jamini; Harpal Singh; Amit Tyagi (AAPS PharmSciTech, 2021)

Poly(Vinyl Alcohol) Cryogel Membranes Loaded with Resveratrol as Potential Active Wound Dressings - Anna Górska; Anna Krupa; Dorota Majda; Piotr Kulinowski; Mateusz Kurek; Władysław P. Węglarz; Renata Jachowicz (AAPS PharmSciTech, 2021)
Hydrogel wound dressings are highly effective in the therapy of wounds. Yet, most of them do not contain any active ingredient that could accelerate healing. The aim of this study was to prepare hydrophilic active dressings loaded with an anti-inflammatory compound - trans-resveratrol (RSV) of hydrophobic properties. A special attention was paid to select such a technological strategy that could both reduce the risk of irritation at the application site and ensure the homogeneity of the final hydrogel. RSV dissolved in Labrasol was combined with an aqueous sol of poly(vinyl) alcohol (PVA), containing propylene glycol (PG) as a plasticizer. This sol was transformed into a gel under six consecutive cycles of freezing (-80 °C) and thawing (RT). White, uniform and elastic membranes were successfully produced. Their critical features, namely microstructure, mechanical properties, water uptake and RSV release were studied using SEM, DSC, MRI, texture analyser and Franz-diffusion cells. The cryogels made of 8 % of PVA showed optimal tensile strength (0.22 MPa) and elasticity (0.082 MPa). The application of MRI enabled to elucidate mass transport related phenomena in this complex system at the molecular (detection of PG, confinement effects related to pore size) as well as at the macro level (swelling). The controlled release of RSV from membranes was observed for 48 h with mean dissolution time of 18 h and dissolution efficiency of 35 %. All in all, these cryogels could be considered as a promising new active wound dressings.

Development and Evaluation of Cocoa Butter Taste Masked Ibuprofen Using Supercritical Carbon Dioxide - Rana Obaidat; Haneen Aleih; Hadeia Mashaqbeh; Bashar Altaani; Mo’tasem M. Alsmadi; Mohammad Alnaief (AAPS PharmSciTech, 2021)

Preformulation Characterization of Griffithsin, a Biopharmaceutical Candidate for HIV Prevention - Lindsay F. Kramzer; Krystal T. Hamorsky; Phillip W. Graebing; Lin Wang; Joshua L. Fuqua; Nobuyuki Matoba; Amanda B. Lasnik; Bernard J. Moncla; Junmei Zhang; Kenneth E. Palmer; Lisa C. Rohan (AAPS PharmSciTech, 2021)

Liquid Crystalline Phases for Enhancement of Oral Bioavailability - Xingwang Zhang; Wei Wu (AAPS PharmSciTech, 2021)

Fabrication of Highly Deformable Bilosomes for Enhancing the Topical Delivery of Terconazole: In Vitro Characterization, Microbiological Evaluation, and In Vivo Skin Deposition Study - Shaimaa Mosallam; Nermin M. Sheta; Ahmed Hassen Elshafeey; Aly Ahmed Abdelbary (AAPS PharmSciTech, 2021)

Enhancement of Therapies for Glioblastoma (GBM) Using Nanoparticle-based Delivery Systems - Kanawat Wiwatchaitawee; Juliana C. Quarterman; Sean M. Geary; Aliasger K. Salem (AAPS PharmSciTech, 2021)

Encapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In Vivo - Treniece L. Terry; Brittany E. Givens; Andrea Adamcakova-Dodd; Peter S. Thorne; Victor G. J. Rodgers; Aliasger K. Salem (AAPS PharmSciTech, 2021)

Physicomechanical, stability, and pharmacokinetic evaluation of aceclofenac dimethyl urea cocrystals - Hafsa Afzal; Nasir Abbas; Amjad Hussain; Sumera Latif; Kanwal Fatima; Muhammad Sohail Arshad; Nadeem Irfan Bukhari (AAPS PharmSciTech, 2021)

A Real-Time NMR Method for Measurement of In Vitro Aggregation Kinetics Of Degarelix Drug Products - Sharadrao M. Patil; Bin Qin; Yan Wang; Snober Ahmed; Huzeyfe Yilmaz; Xiaohui Jiang; David A. Keire; Kang Chen (AAPS PharmSciTech, 2021)

Analysis of Silicone Oil in Prefilled Syringes and Biopharmaceutical Drug Products Using High-Performance Liquid Chromatography - Jian Liu; Mike Ronk; Kiyoshi Fujimori; Hans Lee; Yasser Nashed-Samuel (AAPS PharmSciTech, 2021)

Technological Scenario for Masks in Patent Database During Covid-19 Pandemic - Tatianny de Araújo Andrade; José Adão Carvalho Nascimento Junior; Anamaria Mendonça Santos; Lysandro Pinto Borges; Lucindo José Quintans-Júnior; Cristiani Isabel Banderó Walker; Luiza Abrahão Frank; Mairim Russo Serafini (AAPS PharmSciTech, 2021)

Correction To: Case Study in the Design of a Surrogate Solution for Use in Biopharmaceutical Drug Product Process Development - Kevin Boksa; Peter Walsh; Ambarish Shah (AAPS PharmSciTech, 2021)

Emerging Multi-Drug Eutectics: Opportunities and Challenges - Jamshed Haneef; Shakir Ali; Renu Chadha (AAPS PharmSciTech, 2021)

Elucidating the Splitting Behavior of Tablets to Optimize the Pharmacotherapy in Veterinary Medicine - Giselle R. Bedogni; Felipe Q. Pires; Juliano A. Chaker; Livia L. Sa-Barreto; Katia Seremeta; Nora Okulik; Claudio J. Salomon; Marcilio Cunha-Filho (AAPS PharmSciTech, 2021)

Pluronic-Coated Biogenic Gold Nanoparticles for Colon Delivery of 5-Fluorouracil: In vitro and Ex vivo Studies - Wael A. Mahdi; Afzal Hussain; Mohd Ramzan; Abdul Faruk; Sarah I Bukhari; Abhimanyu Dev (AAPS PharmSciTech, 2021)

Correction to: Investigating Cocrystallization of Carbamazepine with Structurally Compatible Coformers: New Cocrystal and Eutectic Phases with Enhanced Dissolution - Indumathi Sathisaran; Sameer Vishvanath Dalvi (AAPS PharmSciTech, 2021)

Orally Administered Drug Solubility-Enhancing Formulations: Lesson Learnt from Optimum Solubility-Permeability Balance - Bhakti Mahendra Pawar; Syed Nazrin Ruhina Rahman; Datta Maroti Pawde; Abhinab Goswami; Tamilvanan Shunmugaperumal (AAPS PharmSciTech, 2021)

Radiolabeled Tedizolid Phosphate Liposomes for Topical Application: Design, Characterization, and Evaluation of Cellular Binding Capacity - Merve Karpuz; Evren Atlihan-Gundogdu; E. Selin Demir; Zeynep Senyigit (AAPS PharmSciTech, 2021)

A Novel Drug Delivery System: the Encapsulation of Naringenin in Metal-Organic Frameworks into Liposomes - Zhangjie Wang; Lingli Liu; Wei Yin; Ziping Liu; Lingli Shi; Maoxing Tang (AAPS PharmSciTech, 2021)

PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth - Mahmoud S. Hanafy; Stephanie Hufnagel; Andrea N. Trementozzi; Wedad Sakran; Jeanne C. Stachowiak; John J. Koleng; Zhengrong Cui (AAPS PharmSciTech, 2021)

Co-processing of Atorvastatin and Ezetimibe for Enhanced Dissolution Rate: In Vitro and In Vivo Correlation - Mona F. Arafa; Rasha A. Alshaikh; Magdy M. Abdelquader; Gamal M. El Maghraby (AAPS PharmSciTech, 2021)

Molded Vial Manufacturing and Its Impact on Heat Transfer during Freeze-Drying: Vial Geometry Considerations - Tim Wenzel; Henning Gieseler (AAPS PharmSciTech, 2021)
Recent advances in molded vial manufacturing enabled manufacturers to use a new manufacturing technique to achieve superior homogeneity of the vial wall thickness. This study evaluated the influence of the different manufacturing techniques of molded vials and glass compositions on vial heat transfer in freeze-drying. Additionally, the influence of using empty vials as thermal shielding on thermal characteristics of edge and center vials was investigated. The vial heat transfer coefficient K v was determined gravimetrically for multiple vial systems. The results showed superior heat transfer characteristics of the novel manufacturing technique as well as differences in heat transfer for the different glass compositions. Empty vials on the outside of the array did not influence center vial K v values compared to a full array. The direct contact area and vial bottom curvature and their correlation to heat transfer parameters were analyzed across multiple vial systems. A new approach based on light microscopy to describe the vial bottom curvature more accurately was described. The presented results for the contact area allowed for an approximation of the pressure-independent heat transfer parameter KC. The results for the vial bottom curvature showed a great correlation to the pressure-dependent heat transfer parameter KD. Overall, the results highlighted how a thorough geometrical characterization of vials with known heat transfer characteristics could be used to predict thermal characteristics of new vial systems as an alternative to a time-consuming gravimetric K v determination. Primary drying times were simulated to show the influence of K v on drying performance.

RETRACTED ARTICLE: 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, 2021)

New PTX-HS15/T80 Mixed Micelles: Cytotoxicity, Pharmacokinetics and Tissue Distribution - Baoyu Liu; Wei Gao; Hui Wu; Hong Liu; Hongchun Pan (AAPS PharmSciTech, 2021)

Emerging Nanomedicines for the Treatment of Atopic Dermatitis - Khushali Parekh; Tejal A Mehta; Namdev Dhas; Pavan Kumar; Amirali Popat (AAPS PharmSciTech, 2021)

Exploratory Study on Lercanidipine Hydrochloride Polymorphism: pH-Dependent Solubility Behavior and Simulation of its Impact on Pharmacokinetics - Ilia Alekseevich Repin; Raimar Loebenberg; John DiBella; António C. L. Conceição; Manuel E. Minas da Piedade; Humberto G. Ferraz; Michele G. Issa; Nadia A. Bou-Chacra; Catharine F. M. Ermida; Gabriel L. B. de Araujo (AAPS PharmSciTech, 2021)

Recent Advancement in Nanotechnology-Based Drug Delivery System Against Viral Infections - Deepak Pradhan; Prativa Biswasroy; Amit Goyal; Goutam Ghosh; Goutam Rath (AAPS PharmSciTech, 2021)

Improved Oral Bioavailability and Hypolipidemic Effect of Syringic Acid via a Self-microemulsifying Drug Delivery System - Congyong Sun; Wenjing Li; Huiyun Zhang; Michael Adu-Frimpong; Ping Ma; Yuan Zhu; Wenwen Deng; Jiangnan Yu; Ximing Xu (AAPS PharmSciTech, 2021)

Influence of Particle Size and Drug Load on Amorphous Solid Dispersions Containing pH-Dependent Soluble Polymers and the Weak Base Ketoconazole - Marius Monschke; Kevin Kayser; Karl G. Wagner (AAPS PharmSciTech, 2021)
Among the great number of poorly soluble drugs in pharmaceutical development, most of them are weak bases. Typically, they readily dissolve in an acidic environment but are prone to precipitation at elevated pH. This was aimed to be counteracted by the preparation of amorphous solid dispersions (ASDs) using the pH-dependent soluble polymers methacrylic acid ethylacrylate copolymer (Eudragit L100–55) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) via hot-melt extrusion. The hot-melt extruded ASDs were of amorphous nature and single phased with the presence of specific interactions between drug and polymer as revealed by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). The ASDs were milled and classified into six particle size fractions. We investigated the influence of particle size, drug load, and polymer type on the dissolution performance. The best dissolution performance was achieved for the ASD made from Eudragit L100–55 at a drug load of 10%, whereby the dissolution rate was inversely proportional to the particle size. Within a pH-shift dissolution experiment (from pH 1 to pH 6.8), amorphous-amorphous phase separation occurred as a result of exposure to acidic medium which caused markedly reduced dissolution rates at subsequent higher pH values. Phase separation could be prevented by using enteric capsules (Vcaps Enteric®), which provided optimal dissolution profiles for the Eudragit L100–55 ASD at a drug load of 10%.

Development of a Pediatric Mini-Tablet Formulation for Expedited Preclinical Studies - Monika Lavan; Xueqi Wang; Robyn McCain; Amber Jannasch; Bruce Cooper; Scott Hostetler; Stephen Byrn; Gregory Knipp (AAPS PharmSciTech, 2021)

Preparation, Characterization, and In Vitro Pharmacodynamics and Pharmacokinetics Evaluation of PEGylated Urolithin A Liposomes - Shengfu Yi; Cong Zhang; Junjie Hu; Yan Meng; Liang Chen; Huifan Yu; Shan Li; Guihong Wang; Guohua Zheng; Zhenpeng Qiu (AAPS PharmSciTech, 2021)

Phytophospholipid Complex of Caffeic Acid: Development, In vitro Characterization, and In Vivo Investigation of Antihyperlipidemic and Hepatoprotective Action in Rats - Shubhada Mangrulkar; Pranav Shah; Sonali Navnage; Priyanka Mazumdar; Dinesh Chaple (AAPS PharmSciTech, 2021)

Development of Water-Soluble Electrospun Fibers for the Oral Delivery of Cannabinoids - Eleftherios G. Andriotis; Konstantina Chachlioutaki; Paraskevi Kyriaki Monou; Nikolaos Bouropoulos; Dimitrios Tzetzis; Panagiotis Barmpalexis; Ming-Wei Chang; Zeeshan Ahmad; Dimitrios G. Fatouros (AAPS PharmSciTech, 2021)

Promising Antifungal Potential of Engineered Non-ionic Surfactant-Based Vesicles: In Vitro and In Vivo Studies - Amit Verma; Ankit Jain; Ankita Tiwari; Shivani Saraf; Pritish Kumar Panda; Sanjay K. Jain (AAPS PharmSciTech, 2021)

Extracellular Vesicles Derived from a Human Brain Endothelial Cell Line Increase Cellular ATP Levels - Kandarp M. Dave; Wanzhu Zhao; Catherine Hoover; Anisha D’Souza; Devika S Manickam (AAPS PharmSciTech, 2021)

Aerosolization Performance, Antitussive Effect and Local Toxicity of Naringenin-Hydroxypropyl-β-Cyclodextrin Inhalation Solution for Pulmonary Delivery - Minyi Guan; Xuan Zeng; Rui Shi; Yuying Zheng; Weiyang Fan; Weiwei Su (AAPS PharmSciTech, 2021)

Sialic Acid Conjugate–Modified Liposomal Dexamethasone Palmitate Targeting Neutrophils for Rheumatoid Arthritis Therapy: Influence of Particle Size - Shuo Wang; Shuaishuai Yang; Xiaoxue Lai; Yanzhi Song; Ling Hu; Cong Li; Tao Shi; Xinrong Liu; Yihui Deng; Guoliang Chen (AAPS PharmSciTech, 2021)

Evaluation of Microwave Vacuum Drying as an Alternative to Freeze-Drying of Biologics and Vaccines: the Power of Simple Modeling to Identify a Mechanism for Faster Drying Times Achieved with Microwave - Akhilesh Bhambhani; Justin Stanbro; Daniel Roth; Elizabeth Sullivan; Morrisa Jones; Robert Evans; Jeffrey Blue (AAPS PharmSciTech, 2021)
Vial-based lyophilization for biopharmaceuticals has been an indispensable cornerstone process for over 50 years. However, the process is not without significant challenges. Capital costs to realize a lyophilized drug product facility, for example, are very high. Similarly, heat and mass transfer limitations inherent in lyophilization result in drying cycle on the order of several days while putting practical constraints on available formulation space, such as solute mass percentage or fill volume in a vial. Through collaboration with an external partner, we are exploring microwave vacuum drying (MVD) as a faster drying process to vial lyophilization wherein the heat transfer process occurs by microwave radiation instead of pure conduction from the vial. Drying using this radiative process demonstrates greater than 80% reduction in drying time over traditional freeze-drying times while maintaining product activity and stability. Such reduction in freeze-drying process times from days to several hours is a welcome change as it enables flexible manufacturing by being able to better react to changes either in terms of product volume for on-demand manufacturing scenarios or facilities for production ( e.g ., scale-out over scale-up). Additionally, by utilizing first-principle modeling coupled with experimental verification, a mechanism for faster drying times associated with MVD is proposed in this article. This research, to the best of our knowledge, forms the very first report of utilizing microwave vacuum drying for vaccines while utilizing the power of simplified models to understand drying principles associated with MVD.

Equipment Capability Measurement of Laboratory Freeze-Dryers: a Comparison of Two Methods - Jayasree M. Srinivasan; Gregory A. Sacha; Vaibhav Kshirsagar; Alina Alexeenko; Steven L. Nail (AAPS PharmSciTech, 2021)
The objective of this investigation was to evaluate two methods for measuring the maximum sublimation rate that a freeze-dryer will support—the minimum controllable pressure method and the choke point method. Both methods gave equivalent results, but the minimum controllable pressure method is preferred, since it is easier, faster, and less subjective. The ratio of chamber pressure to condenser pressure corresponding to the onset of choked flow was considerably higher in this investigation (up to about 20:1) than in previously published reports. This ratio was not affected by the location of the pressure gauge on the condenser; that is, on the foreline of the vacuum pump versus on the body of the condenser itself. The total water loss due to sublimation as measured by tunable diode laser absorption spectroscopy was consistently within 5% of gravimetrically determined weight loss, regardless of whether the measurement took place during choked versus non-choked process conditions.

Potential Application of USP Paddle and Basket Dissolution Methods in Discriminating for Portioned Moist Snuff and Snus Smokeless Tobacco Products - Ziyaur Rahman; Sathish Dharani; Tahir Khuroo; Mansoor A. Khan (AAPS PharmSciTech, 2021)

Supercritical Fluid Extraction Combined with Ultrahigh Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry for Determination of Extractables to Evaluate Compatibility of Drugs with Rubber Closures - Xuechun Sun; Xin Zheng; Yan Tang; Augustine Atta Debrah; Zhenxia Du (AAPS PharmSciTech, 2021)

3D Printing as a Promising Tool in Personalized Medicine - Vanessa Marcia Vaz; Lalit Kumar (AAPS PharmSciTech, 2021)
Personalized medicine has the potential to revolutionize the healthcare sector, its goal being to tailor medication to a particular individual by taking into consideration the physiology, drug response, and genetic profile of that individual. There are many technologies emerging to cause this paradigm shift from the conventional “one size fits all” to personalized medicine, the major one being three-dimensional (3D) printing. 3D printing involves the establishment of a three-dimensional object, in a layer upon layer manner using various computer software. 3D printing can be used to construct a wide variety of pharmaceutical dosage forms varying in shape, release profile, and drug combination. The major technological platforms of 3D printing researched on in the pharmaceutical sector include inkjet printing, binder jetting, fused filament fabrication, selective laser sintering, stereolithography, and pressure-assisted microsyringe. A possible future application of this technology could be in a clinical setting, where prescriptions could be dispensed based on individual needs. This manuscript points out the various 3D printing technologies and their applications in research for fabricating pharmaceutical products, along with their pros and cons. It also presents its potential in personalized medicine by individualizing the dose, release profiles, and incorporating multiple drugs in a polypill. An insight on how it tends to various populations is also provided. An approach of how it can be used in a clinical setting is also highlighted. Also, various challenges faced are pointed out, which must be overcome for the success of this technology in personalized medicine.

Novel Application of Hot Melt Extrusion Technology for Preparation and Evaluation of Valacyclovir Hydrochloride Ocular Inserts - Gauri Shadambikar; Sushrut Marathe; Akash Patil; Rohit Joshi; Suresh Bandari; Soumyajit Majumdar; Michael Repka (AAPS PharmSciTech, 2021)

Ratiometric Delivery of Mitoxantrone and Berberine Co-encapsulated Liposomes to Improve Antitumor Efficiency and Decrease Cardiac Toxicity - Zimeng Yang; Liwen Zhao; Xue Wang; Zhonggui He; Yongjun Wang (AAPS PharmSciTech, 2021)

Determination and Comparison of the Solubility, Oil–Water Partition Coefficient, Intestinal Absorption, and Biliary Excretion of Carvedilol Enantiomers - Qi Zhang; Xin Wang; Hongjiao Xue; Baolin Huang; Zimin Lin; Zheng Cai (AAPS PharmSciTech, 2021)

Impact of Membranes on In Vitro Release Assessment: a Case Study Using Dexamethasone - Catheleeya Mekjaruskul; André O’Reilly Beringhs; Wei-Chung Luo; Qingguo Xu; Matthew Halquist; Bin Qin; Yan Wang; Xiuling Lu (AAPS PharmSciTech, 2021)

Investigation of Preprocessing and Validation Methodologies for PAT: Case Study of the Granulation and Coating Steps for the Manufacturing of Ethenzamide Tablets - Shojiro Shibayama; Kimito Funatsu (AAPS PharmSciTech, 2021)

Three-Dimensional (3D)–Printed Zero-Order Released Platform: a Novel Method of Personalized Dosage Form Design and Manufacturing - Dongyang Fang; Yining Yang; Mengsuo Cui; Hao Pan; Lijie Wang; Pingfei Li; Wenjing Wu; Sen Qiao; Weisan Pan (AAPS PharmSciTech, 2021)

Preparation of mPEG-b-PLA/TM-2 Micelle Lyophilized Products by Mixed Lyoprotectors and Antitumor Effect In Vivo - Ying Zhang; Yi Liu; Na Wang; Hongbing Liu; Jingxin Gou; Haibing He; Yu Zhang; Tian Yin; Yanjiao Wang; Xing Tang (AAPS PharmSciTech, 2021)

Subcutaneous Injection Performance in Yucatan Miniature Pigs with and without Human Hyaluronidase and Auto-injector Tolerability in Humans - Galen H. Shi; Robert J. Connor; David S. Collins; David W. Kang (AAPS PharmSciTech, 2021)
Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous (SC) delivery of co-administered therapeutic agents by locally and transiently degrading hyaluronan in the SC space, and can be administered with therapeutics using a variety of devices. Two SC delivery studies were carried out to assess auto-injector (AI) performance, each in 18 Yucatan miniature pigs. Abdominal injections were administered using three auto-injectors of 1 mL (AI1) and 2 mL (AI2 and sAI2) with different injection speeds and depths (5.5–7.5 mm) and two pre-filled syringe (PFS) devices of 1 and 2 mL. The injection included a placebo buffer with and without rHuPH20 to evaluate the effect of rHuPH20 on SC injection performance. The feasibility of using similar devices to deliver a placebo buffer in humans was investigated. rHuPH20 was not studied in humans. In miniature pigs, postinjection swelling was evident for most PFS/AI injections, particularly 2 mL. Swelling heights and back leakage were typically lower with rHuPH20 co-administration versus placebo for most device configurations (1 or 2 mL PFS or AI). Auto-injections with versus without rHuPH20 also resulted in reduced swelling firmness and faster swelling resolution over time. Slow injections with rHuPH20 had shorter and more consistent injection time versus placebo. In humans, minimal injection site swelling and negligible back leakage were observed for 2-mL injections of placebo, while more erythema was observed in humans versus miniature pigs. Even at high delivery rates with PFS or AI, the addition of rHuPH20 resulted in improved SC injection performance versus placebo in miniature pigs.

Multifunctional Role of Polyvinylpyrrolidone in Pharmaceutical Formulations - Yu Luo; Yanlong Hong; Lan Shen; Fei Wu; Xiao Lin (AAPS PharmSciTech, 2021)

Sirolimus-Loaded Intravitreal Implant for Effective Treatment of Experimental Uveitis - Mayara Rodrigues Brandão De Paiva; Daniel Vítor Vasconcelos-Santos; Lorena Carla Vieira; Sílvia Ligório Fialho; Armando Silva-Cunha (AAPS PharmSciTech, 2021)

Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines - Yves Marc Dupertuis; Nathalie Boulens; Emmanuelle Angibaud; Anna-Sophia Briod; Alexandre Viglione; Eric Allémann; Florence Delie; Claude Pichard (AAPS PharmSciTech, 2021)
It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.19 ± 0.03 and zeta potential of -41 ± 2 mV. They contained 557 ± 210 μmol/l DHA, 1467 ± 362 μmol/l EPA, and 9.8 ± 1.1 μmol/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and LIPU in both LS174T (p53 +/+ , bax −/− ) and HT-29 (p53 −/0 , bax +/+ ) cell lines. Similar to LIFU, LIPUFU increased the percentage of cells in S phase, apoptosis, and/or necrosis. The cytotoxic potential of LIPUFU was confirmed in vivo by tumor growth inhibition in the chicken chorioallantoic membrane model. These results suggest that LIPUFU could be considered to facilitate the simultaneous transport of 5-FU and n-3 PUFAs to the tumor site, in particular in case of CRC liver metastases.

Effect of Different Nail Penetration Enhancers in Solid Lipid Nanoparticles Containing Terbinafine Hydrochloride for Treatment of Onychomycosis - Fatma E. Abobakr; Sahar M. Fayez; Vivian S. Elwazzan; Wedad Sakran (AAPS PharmSciTech, 2021)

Salt Engineering of Aripiprazole with Polycarboxylic Acids to Improve Physicochemical Properties - Hamideh Afrooz; Eman M. Mohamed; Sogra F. Barakh Ali; Sathish Dharani; Mohammad T. H. Nutan; Mansoor A. Khan; Ziyaur Rahman (AAPS PharmSciTech, 2021)

Characterization and Systemic Delivery of Dibenzoylmethane via the Intranasal Route - Deepal Vora; Anthony E. Kincaid; Justin Tolman; Harsh Chauhan (AAPS PharmSciTech, 2021)

Investigating Cocrystallization of Carbamazepine with Structurally Compatible Coformers: New Cocrystal and Eutectic Phases with Enhanced Dissolution - Indumathi Sathisaran; Sameer Vishvanath Dalvi (AAPS PharmSciTech, 2021)

Case Study in the Design of a Surrogate Solution for Use in Biopharmaceutical Drug Product Process Development - Kevin Boksa; Peter Walsh; Ambarish Shah (AAPS PharmSciTech, 2021)