AAPS PharmSciTech最新文献

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A Novel Felbinac Transdermal Patch with High Permeability: Design, Development and Evaluation 新型高透性Felbinac透皮贴剂的设计、研制与评价
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-10-04 DOI: 10.1208/s12249-025-03227-z
Li Qin, Cheng Liu, Ran Bai, Zhining Zhao, Yinghua Sun, Peng Zhang
{"title":"A Novel Felbinac Transdermal Patch with High Permeability: Design, Development and Evaluation","authors":"Li Qin,&nbsp;Cheng Liu,&nbsp;Ran Bai,&nbsp;Zhining Zhao,&nbsp;Yinghua Sun,&nbsp;Peng Zhang","doi":"10.1208/s12249-025-03227-z","DOIUrl":"10.1208/s12249-025-03227-z","url":null,"abstract":"<div><p>The objective of the work was to design a novel felbinac transdermal patch to improve its transdermal delivery efficiency by adding chemical penetration enhancers. The adhesion properties and <i>in vitro</i> transdermal release performance were first evaluated. The transdermal stability and skin irritation were then evaluated. Moreover, <i>in vivo</i> tissue distribution was also examined. The novel felbinac transdermal patch with high adhesion was prepared by calendar coating method. Different types of chemical enhancers and their amount on <i>in vitro</i> transdermal delivery efficiency were systematically screened. <i>In vitro</i> transdermal release experiments showed that by adding 1% propylene glycol (PG) as penetration enhancers, the cumulative transdermal amount of the transdermal patch within 12 h was 189.03 μg/cm<sup>2</sup>, which was twice that of commercial product SELTOUCH® (94.44 μg/cm<sup>2</sup>). In addition, the transdermal patch still maintained stable permeability after being stored at room temperature for 4 months and also had good safety. Further, <i>in vivo</i> experiments confirmed that the concentration of felbinac in plasma, skin, and muscle tissues was significantly increased following administration of the self-made transdermal patch compared to SELTOUCH®. In conclusion, the felbinac transdermal patch developed in this study demonstrated high adhesion, excellent transdermal delivery efficiency and good stability, representing a transdermal drug delivery system with great clinical application potential.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in Pharmaceutical Cocrystals and Nano-Cocrystals: Strategies for Enhancing Solubility and Translating to Clinical Use 药物共晶和纳米共晶的研究进展:提高溶解度和转化为临床应用的策略
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-10-04 DOI: 10.1208/s12249-025-03228-y
Roshan P. Rao, Jawahar Natarajan, Samanwita Khanra, Jey Kumar Pachiyappan, Imrankhan Nizam, Akshay Muralidhara, Jubie Selvaraj, S. Selvamuthukumar
{"title":"Advances in Pharmaceutical Cocrystals and Nano-Cocrystals: Strategies for Enhancing Solubility and Translating to Clinical Use","authors":"Roshan P. Rao,&nbsp;Jawahar Natarajan,&nbsp;Samanwita Khanra,&nbsp;Jey Kumar Pachiyappan,&nbsp;Imrankhan Nizam,&nbsp;Akshay Muralidhara,&nbsp;Jubie Selvaraj,&nbsp;S. Selvamuthukumar","doi":"10.1208/s12249-025-03228-y","DOIUrl":"10.1208/s12249-025-03228-y","url":null,"abstract":"<div><p>Poor oral bioavailability in most modern pharmaceuticals is primarily caused by poor aqueous solubility. Most NCEs (New Chemical Entities) and nearly 40% of drugs on the market fall into either Biopharmaceutical Classification System (BCS) class II or IV, both characterized by very poor aqueous solubility. This leads to a higher demand for techniques that improve solubility in water-based media. This study aims to compile and present a comprehensive and detailed assessment of cocrystals and nano-cocrystals. It emphasizes the importance of in-depth research into nano-cocrystals to gather more raw data, which will support the eventual translation of nano-cocrystals into clinical use and market approval. Cocrystal technology has been used to enhance various physicochemical parameters, including stability, solubility, and bioavailability. Nano-cocrystallization is a new emerging technique that combines the benefits of cocrystallization with nanosizing, resulting in cocrystals with improved physicochemical properties and increased surface area due to nanoscale particles. These methods not only enhance aqueous solubility but have also been shown to directly increase the dissolution rate and improve the dissolution profile of drug substances. A literature review was conducted using PubMed, Scopus, and patent databases. Cocrystals and multicomponent systems are discussed with an emphasis on their crystal structure, types and nature of bonds formed, and any significant variations or special characteristics are highlighted. This thorough review offers an overview of cocrystals and nano-cocrystals, outlining the cocrystallization process and various methods for formulation and characterization. It also covers the selection process for coformers, including new computational, AI, and machine learning techniques for screening. The review introduces nano-cocrystals, describing their synthesis methods and benefits. It discusses polymorphism in both cocrystals and nano-cocrystals, and compares cocrystals as a way to improve solubility. Additionally, it evaluates their different applications and clinical outcomes. The discussion points out that the limited research on nano-cocrystals hinders their translation into industrial and clinical use. In contrast, cocrystals, despite some barriers, have achieved notable commercial success.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhalable Inclusion Cocrystal of Exocarpium Citri Grandis Volatile Oil for Treatment of Acute Lung Injury 柑桔挥发油可吸入包涵共晶治疗急性肺损伤
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-26 DOI: 10.1208/s12249-025-03224-2
Ying Luo, Zeyu Li, Guilan Wang, Ergang Liu, Huan Shen, Guilong Zhao, Ping Zhao, Yongzhuo Huang
{"title":"Inhalable Inclusion Cocrystal of Exocarpium Citri Grandis Volatile Oil for Treatment of Acute Lung Injury","authors":"Ying Luo,&nbsp;Zeyu Li,&nbsp;Guilan Wang,&nbsp;Ergang Liu,&nbsp;Huan Shen,&nbsp;Guilong Zhao,&nbsp;Ping Zhao,&nbsp;Yongzhuo Huang","doi":"10.1208/s12249-025-03224-2","DOIUrl":"10.1208/s12249-025-03224-2","url":null,"abstract":"<div><p>Acute lung injury (ALI) is the major cause of respiratory failure, often triggered by inflammatory responses resulting in disruption of the pulmonary gas-blood barrier. Existing treatments are limited by the poor bioavailability via systemic administration, whereas volatile oils are unsuitable for developing into inhalable formulations. In this study, we developed an inhalable cocrystal of Exocarpium <i>Citri Grandis</i> volatile oil (EVO) using crystallization technology with β-cyclodextrin (EVO-βCD), aiming to improve the drug’s bioavailability and enhance its therapeutic efficacy for ALI. <i>In vitro</i> studies revealed that EVO-βCD exhibited no significant cytotoxicity at concentrations of 7.5–120.0 µg/mL and did not cause hemolysis at concentrations between 3.75–60.0 µg/mL, suggesting favorable safety profiles. Additionally, EVO and EVO-βCD significantly reduced the ROS production in LPS pretreated 16HBE cells, highlighting their antioxidant potential. <i>In vivo</i> experiments demonstrated that EVO-βCD cocrystals were more effective than free EVO in reducing inflammatory cytokines (TNF-α, IL-1β, IL-6) and improving pulmonary edema in LPS-induced acute lung injury in mice. The cocrystal formulation enhanced the release rate of the drug, addressing the challenges of conventional powder inhalants. These findings suggest that EVO-βCD cocrystals hold promise as a novel therapeutic approach for ALI treatment with enhanced safety and efficacy.</p><h3>Graphical Abstract</h3><p>The study presents a novel approach for treating acute lung injury (ALI) using a cocrystal formulation of volatile oil from Exocarpium <i>Citri Grandis</i> (EVO) encapsulated by β-cyclodextrin (EVO-βCD).</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145170194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Formulation and Optimization of Memantine-Loaded PEGylated Single-Walled Carbon Nanotube Dispersions 负载memantine的聚乙二醇单壁碳纳米管分散体的制备与优化
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-19 DOI: 10.1208/s12249-025-03194-5
Hoa Le, Hai V. Nguyen, Amos Abioye, Adeboye Adejare
{"title":"Formulation and Optimization of Memantine-Loaded PEGylated Single-Walled Carbon Nanotube Dispersions","authors":"Hoa Le,&nbsp;Hai V. Nguyen,&nbsp;Amos Abioye,&nbsp;Adeboye Adejare","doi":"10.1208/s12249-025-03194-5","DOIUrl":"10.1208/s12249-025-03194-5","url":null,"abstract":"<div><p>The study aimed to develop stable single-walled carbon nanotube (SWCNT) dispersions in water that exhibit low protein adsorption in biological media, entrap Memantine, and release the drug in a controlled manner. Specifically, SWCNTs were functionalized, initially oxidized, and then non-covalently conjugated with pyrene methoxy polyethylene glycols (PEG). Dynamic light scattering, Raman spectroscopy, and Fourier-transform infrared spectroscopy were used to evaluate various physicochemical properties of PEG functionalized SWCNTs (PEGSWCNTs). A D-optimal design, utilizing JMP Pro 16, was employed to design the experiment and investigate the effects of oxidation time and PEG concentration on the physicochemical properties of SWCNT dispersions. The optimal dispersions exhibited hydrodynamic particle sizes, polydispersity indices, and zeta potentials ranging from 157.5 to 204.4 nm, 0.231 to 0.255, and -27.8 to -18.8 mV, respectively. The interaction between serum proteins and PEGSWCNTs was evaluated using dynamic light scattering, bicinchoninic acid, and sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The serum protein–SWCNT interaction was significantly reduced due to the presence of PEGs, depending on PEG concentrations, the ratio of long-chain PEG molecules to short-chain PEG molecules, and the physicochemical properties of PEGSWCNT dispersions. Finally, Memantine was incorporated into the optimal PEGSWCNT dispersions. The entrapment efficiency, drug loading, and drug release from the dispersions were evaluated using gas chromatography with flame ionization detection (GC/FID). The results indicated that PEGSWCNT particles could entrap Memantine. The <i>in vitro</i> drug release profile exhibited an extended release over 3 to 7 h, with a significant burst release occurring in the first hour (more than 50%). Higher PEG density and a higher PEG20K/2K ratio exhibited slower drug release rates. The release profiles of the formulations using 40% PEG were fitted to the Weibull model, indicating that Memantine release from the SWCNT dispersions followed a Fickian diffusion mechanism.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Factors Influencing the Dispersibility of Glycopyrronium Bromide and Indacaterol Maleate – Combined In Vitro and In Silico Study 影响甘溴铵与马来酸吲哚卡特罗复合分散的因素——体外和硅内研究
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-18 DOI: 10.1208/s12249-025-03182-9
Aleksandra Rzewińska, Jakub Szlęk, Ewelina Juszczyk, Katarzyna Mróz, Olga Czerepow-Bielik, Maciej Wieczorek, Przemysław Dorożyński
{"title":"Factors Influencing the Dispersibility of Glycopyrronium Bromide and Indacaterol Maleate – Combined In Vitro and In Silico Study","authors":"Aleksandra Rzewińska,&nbsp;Jakub Szlęk,&nbsp;Ewelina Juszczyk,&nbsp;Katarzyna Mróz,&nbsp;Olga Czerepow-Bielik,&nbsp;Maciej Wieczorek,&nbsp;Przemysław Dorożyński","doi":"10.1208/s12249-025-03182-9","DOIUrl":"10.1208/s12249-025-03182-9","url":null,"abstract":"<div><p>The development of dry powder inhalers (DPIs) for pulmonary drug delivery is complex, requiring optimization of variable factors to ensure effective lung deposition. This study investigates the factors influencing the dispersibility of glycopyrronium bromide (GLP) and indacaterol maleate (IND) in adhesive mixtures using both in vitro and in silico approaches. The formulation was designed to match the reference listed drug (RLD), using lactose and magnesium stearate as excipients. Key variables examined included mixing energy, carrier particle size distribution (PSD), and active pharmaceutical ingredient (API) particle size characteristics across multiple suppliers.</p><p>A Next Generation Impactor (NGI) was employed to assess the aerodynamic particle size distribution (APSD) of 67 formulations. The collected impactor data were analyzed using machine learning (ML) models, leveraging the h2o AutoML framework. Stacked ensemble models demonstrated high predictive accuracy (R<sup>2</sup>: 0.940 for GLP, 0.969 for IND), identifying key formulation parameters affecting dispersibility. SHAP analysis revealed that GLP dispersibility was influenced primarily by GLP PSD (d90, d50, SPAN), lactose d10, and mixing energy, while IND was more dependent on lactose PSD and its own particle size.</p><p>The findings confirm that both APIs interact with each other within the formulation, significantly impacting their reciprocal deposition profiles. These insights highlight the challenge of developing bioequivalent DPI formulations and emphasize the importance of PSD control, mixing energy optimization, and advanced ML modeling in predicting therapeutic equivalence. The study provides a predictive framework to support the development of generic inhalation products, improving regulatory approval pathways and ensuring effective pulmonary drug delivery.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03182-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Fundamentals of the Analysis of Cascade Impactor Data for the Characterization of Aerodynamic Particle Size Distributions (APSDs) in the Testing of Orally Inhaled Drug Products (OIPs) 口服吸入药物测试中空气动力学粒径分布(apsd)的级联冲击数据分析的基础
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-18 DOI: 10.1208/s12249-025-03211-7
Daryl L. Roberts, Jolyon P. Mitchell
{"title":"The Fundamentals of the Analysis of Cascade Impactor Data for the Characterization of Aerodynamic Particle Size Distributions (APSDs) in the Testing of Orally Inhaled Drug Products (OIPs)","authors":"Daryl L. Roberts,&nbsp;Jolyon P. Mitchell","doi":"10.1208/s12249-025-03211-7","DOIUrl":"10.1208/s12249-025-03211-7","url":null,"abstract":"<div><p>The multi-stage cascade impactor (CI) is the recognized apparatus for the characterization of the aerodynamic particle size distribution (APSD) of aerosols emitted from all classes of orally inhaled products. There is presently a mixed level of understanding in the community of those evaluating inhaler performance about the fundamentals of how these apparatuses accomplish their particle size fractionation and therefore how to analyze their data in a technically correct and meaningful manner. The purpose of this article, therefore, is first to set out how the CI functions from the standpoint of the underlying physical processes associated with inertial size fractionation. The explanation of these size fractionation processes describes the relationship of the mass of active pharmaceutical ingredient to particle aerodynamic size. Second, based on these fundamentals, a detailed analysis is provided in support of calculating in a technically correct manner the cascade impactor-derived estimation of metrics describing the APSD. In a comprehensive Supplemental Information packet, the underlying mathematical principles are explained that govern both arithmetic and geometric forms of the traditional assumed shapes that the APSD may take when deriving measures in support of inhaler performance assessments.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Vivo Pharmacodynamic and Pharmacokinetic Assessment of Cannabidiol-loaded Camel Milk Exosomes in Doxorubicin-resistant Triple-negative Breast Cancer Xenografts 负载大麻二酚的骆驼乳外泌体在耐多柔比星三阴性乳腺癌异种移植中的体内药效学和药代动力学评估
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-11 DOI: 10.1208/s12249-025-03201-9
Mounika Aare, Sandeep Chary Padakanti, Mandip Singh
{"title":"In Vivo Pharmacodynamic and Pharmacokinetic Assessment of Cannabidiol-loaded Camel Milk Exosomes in Doxorubicin-resistant Triple-negative Breast Cancer Xenografts","authors":"Mounika Aare,&nbsp;Sandeep Chary Padakanti,&nbsp;Mandip Singh","doi":"10.1208/s12249-025-03201-9","DOIUrl":"10.1208/s12249-025-03201-9","url":null,"abstract":"<div><p>Cannabidiol (CBD) suffers from poor aqueous solubility and extensive first-pass metabolism, which significantly limits its oral bioavailability. In our earlier work, we developed camel milk-derived exosomes (CMDE) as nanocarriers to enhance CBD bioavailability, confirmed through in vivo pharmacokinetic evaluations. In this study, we further characterized the formulation by performing an in silico physiologically based pharmacokinetic (PBPK) simulation using GastroPlus™, integrating in vitro dissolution data. The simulation demonstrated that CBD absorption improved markedly with exosomal encapsulation, achieving 97.8% compared to 13.1% for free CBD. Additionally, CBD-exosomes produced an 8.66-fold increase in maximum plasma concentration (Cmax) and a 7.15-fold increase in the area under the curve (AUC), with predominant uptake observed in the duodenum and jejunum. These computational findings closely mirrored our in vivo results, providing mechanistic insights into the enhanced oral absorption of CBD via exosomal encapsulation. Furthermore, in vitro cytotoxicity studies revealed that combining CBD-CMDE with Paclitaxel (PTX) produced synergistic effects, enabling a two-fold reduction in the required PTX dose. In MDA-MB-231 DOX RT xenograft models, the combination of CBD-CMDE and PTX reduced tumor burden by 2.5-fold relative to controls. Western blot analyses indicated significant downregulation of PI3K/AKT/mTOR pathway regulators, along with modulation of immune markers, suggesting an immune-activating component. Whole-body imaging further confirmed the in vivo targetability of CMDE. This study represents the first application of PBPK modeling, based on in vitro dissolution data, to assess the pharmacokinetics of CBD-exosomes. By integrating computational and preclinical evidence, our findings underscore the potential of exosome-based oral drug delivery systems in enhancing therapeutic efficacy.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Amorphization of Albendazole Using Organic Acid-based Solid Dispersions for Improved Dissolution: A Solvent-free Approach 用有机酸基固体分散体改善阿苯达唑的非晶化溶解:无溶剂方法
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-11 DOI: 10.1208/s12249-025-03223-3
Nilesh Jambukiya, Kiran Dudhat, Sunny shah, Chetan Borkhataria, Trupesh Pethani, Ramesh Parmar, Viral Shah, Gaurav Sanghvi, Mori Dhaval
{"title":"Amorphization of Albendazole Using Organic Acid-based Solid Dispersions for Improved Dissolution: A Solvent-free Approach","authors":"Nilesh Jambukiya,&nbsp;Kiran Dudhat,&nbsp;Sunny shah,&nbsp;Chetan Borkhataria,&nbsp;Trupesh Pethani,&nbsp;Ramesh Parmar,&nbsp;Viral Shah,&nbsp;Gaurav Sanghvi,&nbsp;Mori Dhaval","doi":"10.1208/s12249-025-03223-3","DOIUrl":"10.1208/s12249-025-03223-3","url":null,"abstract":"<div><p>Albendazole (ABZ), a broad-spectrum anthelmintic drug, exhibits poor aqueous solubility and low oral bioavailability (&lt; 5%), limiting its therapeutic effectiveness. This study introduces an organic solvent-free strategy to enhance ABZ dissolution by preparing solid dispersions (SDs) with weak organic acids—citric acid (CA), tartaric acid (TA), and glutaric acid (GA). pH-dependent solubility analysis showed that all three acids improved ABZ solubility, with CA achieving the most pronounced effect—a 188,000-fold increase compared to intrinsic solubility of ABZ (0.25 µg/mL). SDs were formulated at varying ABZ-to-acid molar ratios (1:0.5 to 1:3) using concentrated acid solutions, followed by drying. PXRD confirmed complete amorphization of ABZ in CA-based SDs at 1:1 and higher ratios, while TA and GA resulted in partial amorphization. FTIR and solution-phase <sup>1</sup>H NMR revealed hydrogen bond formation between ABZ and CA, which contributed to the stabilization of the amorphous form and maintenance of supersaturation. Step dissolution studies demonstrated significantly enhanced drug release from CA-based SDs, with 100% cumulative percentage drug dissolved (CPDD) in acidic medium (0.1 N HCl), and up to 80% for TA-based SDs compared to pure ABZ. At pH 6.8, CA-based SDs formed stable colloidal suspensions for up to one hour before phase separation. Stability studies under accelerated conditions (40°C/75% RH, 30 days) confirmed the amorphous stability of CA-based SDs at 1:2 and 1:3 ratios. The study presents a cost-effective and scalable solvent-free formulation approach using organic acids to prepare SD, aimed at enhancing the dissolution of ABZ, with potential applicability to other poorly water-soluble drug.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated Analytical Techniques to Investigate the Effect of the Freezing/Thawing Cycles on the Non-replicating Recombinant Chimpanzee Adenovirus Viral Vector COVID-19 Vaccine 冻融循环对重组黑猩猩腺病毒载体COVID-19疫苗影响的综合分析技术研究
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-10 DOI: 10.1208/s12249-025-03220-6
Moushira M. Mostafa, Nourhan H. AbdelAllah, Eman S. Elzanfaly, Ghada A. Sedik
{"title":"Integrated Analytical Techniques to Investigate the Effect of the Freezing/Thawing Cycles on the Non-replicating Recombinant Chimpanzee Adenovirus Viral Vector COVID-19 Vaccine","authors":"Moushira M. Mostafa,&nbsp;Nourhan H. AbdelAllah,&nbsp;Eman S. Elzanfaly,&nbsp;Ghada A. Sedik","doi":"10.1208/s12249-025-03220-6","DOIUrl":"10.1208/s12249-025-03220-6","url":null,"abstract":"<div><p>The <i>chimpanzee </i><i>adenovirus-vectored vaccine</i> developed by the <i>University of Oxford</i> (ChAdOx1 nCoV-19) showed good stability when stored in refrigerator. However, the vaccine manufacturer prefers its transportation in frozen condition. Data regarding the stability of the vaccine after exposure to repeated freezing processes have not been explored yet. In the present study, different batches were exposed to 3 repeated freezing/thawing cycles. An orthogonal testing using various techniques was employed to assess any induced changes in the properties of the vaccine in comparison with control samples. Physicochemical properties, including appearance, pH, and molecular size distribution by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were evaluated. Anion-exchange chromatography (AEC) was used for the determination of virus particles, and DNA to-protein ratio to study the biochemical attributes of the vaccine. Furthermore, the immunological properties were evaluated employing <i>in-vivo</i> test to compare the results obtained by the testing protocol to the vaccine efficiency in animals. Results revealed that the physicochemical attributes of the vaccine were not affected by the applied freeze–thaw cycles. Although the virus particles measured for thawed samples by AEC were below the specified limits of 0.7 – 1.3 × 10<sup>11</sup> VP/mL, the values of DNA to protein ratio remained unaffected (1.1 – 1.5), and there was no reduction in the <i>in vivo</i> potency of the tested samples. Statistical analysis of the results of the quantitative tests implied that the vaccine could withstand up to three successive freezing and thawing cycles during transportation without significant loss in its structural integrity and biological potency. </p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03220-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction Note: Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid 烷基链修饰聚丙烯亚胺(PPI)作为非病毒载体用于阿霉素和TRAIL质粒共递送的效率评价
IF 4 4区 医学
AAPS PharmSciTech Pub Date : 2025-09-03 DOI: 10.1208/s12249-025-03229-x
Mahboubeh Ebrahimian, Sahar Taghavi, Maryam Ghoreishi, Shahrzad Sedghi, Sara Amel Farzad, Mohammad Ramezani, Maryam Hashemi
{"title":"Retraction Note: Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid","authors":"Mahboubeh Ebrahimian,&nbsp;Sahar Taghavi,&nbsp;Maryam Ghoreishi,&nbsp;Shahrzad Sedghi,&nbsp;Sara Amel Farzad,&nbsp;Mohammad Ramezani,&nbsp;Maryam Hashemi","doi":"10.1208/s12249-025-03229-x","DOIUrl":"10.1208/s12249-025-03229-x","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 7","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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