Pinal Chaudhari, Vivek M Ghate, Arun K Kodoth, Sumit Birangal, Shaila A Lewis
{"title":"口服环孢素A的药物-硅-纤维素三元基质:体外和体内评价。","authors":"Pinal Chaudhari, Vivek M Ghate, Arun K Kodoth, Sumit Birangal, Shaila A Lewis","doi":"10.1080/10837450.2024.2448625","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation <i>via</i> molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored. The present study aimed to explore the impact of MS and a hydroxypropyl methylcellulose (HPMC) matrix on the supersaturation and bioavailability of the neutral drug CsA.</p><p><strong>Methods: </strong>A CsA-loaded mesoporous silica/HPMC ternary matrix and CsA-HPMC and CsA-MS controls were prepared, and physicochemical characterization was carried out. The ternary matrix and controls were investigated for the Non-sink Mini FaSSIF dissolution and biorelevant transfer studies. Furthermore, drug release modeling was performed using DDSolver, and pharmacokinetic studies were performed to assess the impact on oral bioavailability compared with the marketed formulation.</p><p><strong>Results: </strong>The study suggested that the co-loaded CsA, HPMC, and MS demonstrated higher supersaturation than CsA-loaded silica and CsA-HPMC controls. A significant improvement in FaSSIF single medium (2-fold) and biorelevant transfer (3.37-fold) increase in the dissolution profile was observed for the co-loaded CsA-MS-HPMC samples. The <i>in vitro</i> dissolution profile was corroborated by pharmacokinetic studies, which showed a 1.19-fold higher oral bioavailability of CsA-MS-HPMC compared to that of CsA-MS and CsA-HPMC.</p><p><strong>Conclusion: </strong>The pharmacokinetics indicated that CsA-MS-HPMC co-loaded samples demonstrated supersaturation and improved bioavailability compared with the physical mixture.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"114-125"},"PeriodicalIF":2.6000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Drug-silica-cellulose ternary matrix for the oral delivery of Cyclosporine A: <i>in vitro</i> and <i>in vivo</i> evaluation.\",\"authors\":\"Pinal Chaudhari, Vivek M Ghate, Arun K Kodoth, Sumit Birangal, Shaila A Lewis\",\"doi\":\"10.1080/10837450.2024.2448625\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation <i>via</i> molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored. The present study aimed to explore the impact of MS and a hydroxypropyl methylcellulose (HPMC) matrix on the supersaturation and bioavailability of the neutral drug CsA.</p><p><strong>Methods: </strong>A CsA-loaded mesoporous silica/HPMC ternary matrix and CsA-HPMC and CsA-MS controls were prepared, and physicochemical characterization was carried out. The ternary matrix and controls were investigated for the Non-sink Mini FaSSIF dissolution and biorelevant transfer studies. Furthermore, drug release modeling was performed using DDSolver, and pharmacokinetic studies were performed to assess the impact on oral bioavailability compared with the marketed formulation.</p><p><strong>Results: </strong>The study suggested that the co-loaded CsA, HPMC, and MS demonstrated higher supersaturation than CsA-loaded silica and CsA-HPMC controls. A significant improvement in FaSSIF single medium (2-fold) and biorelevant transfer (3.37-fold) increase in the dissolution profile was observed for the co-loaded CsA-MS-HPMC samples. The <i>in vitro</i> dissolution profile was corroborated by pharmacokinetic studies, which showed a 1.19-fold higher oral bioavailability of CsA-MS-HPMC compared to that of CsA-MS and CsA-HPMC.</p><p><strong>Conclusion: </strong>The pharmacokinetics indicated that CsA-MS-HPMC co-loaded samples demonstrated supersaturation and improved bioavailability compared with the physical mixture.</p>\",\"PeriodicalId\":20004,\"journal\":{\"name\":\"Pharmaceutical Development and Technology\",\"volume\":\" \",\"pages\":\"114-125\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Development and Technology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/10837450.2024.2448625\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Development and Technology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10837450.2024.2448625","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
目的:利用介孔二氧化硅(MS)通过分子吸附产生过饱和,以提高药物的口服生物利用度,已被广泛探索过饱和配方;然而,随之而来的是降水。几种沉淀抑制剂(PI)已被探索,以防止沉淀和保持药物在溶液中较长的时间。然而,MS和pi的结合方法、MS和Silica的影响以及环孢素A (Cyclosporine A, CsA)等高分子量中性分子的负载等方面的研究尚未深入。本研究旨在探讨质谱和羟丙基甲基纤维素(HPMC)基质对中性药物CsA过饱和度和生物利用度的影响。方法:制备csa负载介孔二氧化硅/HPMC三元基体,CsA-HPMC和CsA-MS对照,并进行理化表征。对三元基质和对照进行了非沉淀迷你FaSSIF溶解和生物相关转移研究。此外,使用DDSolver进行药物释放建模,并进行药代动力学研究,以评估与市售制剂相比对口服生物利用度的影响。结果:研究表明,共负载CsA、HPMC和MS的过饱和度高于CsA负载二氧化硅和CsA-HPMC的对照。在共载CsA-MS-HPMC样品中,FaSSIF单培养基(2倍)和生物相关转移(3.37倍)的溶解谱显著改善。药代动力学研究证实了CsA-MS- hpmc的体外溶出谱,表明CsA-MS- hpmc的口服生物利用度比CsA-MS和CsA-HPMC高1.19倍。结论:CsA-MS-HPMC共载样品的药代动力学表明,CsA-MS-HPMC共载样品与物理混合物相比具有过饱和度,生物利用度提高。
Drug-silica-cellulose ternary matrix for the oral delivery of Cyclosporine A: in vitro and in vivo evaluation.
Purpose: Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation via molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored. The present study aimed to explore the impact of MS and a hydroxypropyl methylcellulose (HPMC) matrix on the supersaturation and bioavailability of the neutral drug CsA.
Methods: A CsA-loaded mesoporous silica/HPMC ternary matrix and CsA-HPMC and CsA-MS controls were prepared, and physicochemical characterization was carried out. The ternary matrix and controls were investigated for the Non-sink Mini FaSSIF dissolution and biorelevant transfer studies. Furthermore, drug release modeling was performed using DDSolver, and pharmacokinetic studies were performed to assess the impact on oral bioavailability compared with the marketed formulation.
Results: The study suggested that the co-loaded CsA, HPMC, and MS demonstrated higher supersaturation than CsA-loaded silica and CsA-HPMC controls. A significant improvement in FaSSIF single medium (2-fold) and biorelevant transfer (3.37-fold) increase in the dissolution profile was observed for the co-loaded CsA-MS-HPMC samples. The in vitro dissolution profile was corroborated by pharmacokinetic studies, which showed a 1.19-fold higher oral bioavailability of CsA-MS-HPMC compared to that of CsA-MS and CsA-HPMC.
Conclusion: The pharmacokinetics indicated that CsA-MS-HPMC co-loaded samples demonstrated supersaturation and improved bioavailability compared with the physical mixture.
期刊介绍:
Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology.
Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as:
-Preformulation and pharmaceutical formulation studies
-Pharmaceutical materials selection and characterization
-Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation
-QbD in the form a risk assessment and DoE driven approaches
-Design of dosage forms and drug delivery systems
-Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies
-Drug delivery systems research and quality improvement
-Pharmaceutical regulatory affairs
This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.