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Experimental study of ketoconazole impregnation into polyvinyl pyrrolidone and hydroxyl propyl methyl cellulose using supercritical carbon dioxide: Process optimization
The Journal of Supercritical Fluids ( IF 3.9 ) Pub Date : 2022-06-22 , DOI: 10.1016/j.supflu.2022.105674
Mostafa Fathi , Gholamhossein Sodeifian , Seyed Ali Sajadian

This study aims to increase the oral bioavailability of ketoconazole (KET, drug) by incorporating it into water-soluble polymers, using supercritical carbon dioxide (SC-CO2) as the impregnating solvent. For this purpose, loading of KET into poly (vinylpyrrolidone) (PVP) and hydroxy propyl methyl cellulose (HPMC) using supercritical solvent impregnation (SSI) was investigated for the first time. Box-Behnken design (BBD) was used to optimize the impregnation process. Effects of three process parameters, namely pressure (150, 200 and 250 bar), impregnation time (60, 120 and 180 min), and temperature (308, 318 and 328 K) on the loading were studied, leading to a range of 0.33%− 0.98% for KET into PVP and 0.46%− 1.41% for KET into HPMC polymer. Samples were examined using FTIR, DLS, SEM, XRD and DSC analyses. Additionally, the small particle size and the presence of polymers increased the dissolution rate of the drug in aqueous solutions up to 7.3 folds.



中文翻译:

超临界二氧化碳对酮康唑浸渍聚乙烯吡咯烷酮和羟丙基甲基纤维素的实验研究:工艺优化

本研究旨在通过使用超临界二氧化碳(SC-CO 2) 作为浸渍溶剂。为此,首次研究了使用超临界溶剂浸渍 (SSI) 将 KET 负载到聚 (乙烯基吡咯烷酮) (PVP) 和羟丙基甲基纤维素 (HPMC) 中。Box-Behnken 设计 (BBD) 用于优化浸渍过程。研究了三个工艺参数,即压力(150、200 和 250 bar)、浸渍时间(60、120 和 180 分钟)和温度(308、318 和 328 K)对负载的影响,得出的范围为 0.33 %− 0.98% 的 KET 转化为 PVP,0.46%− 1.41% 的 KET 转化为 HPMC 聚合物。使用 FTIR、DLS、SEM、XRD 和 DSC 分析检查样品。此外,小粒径和聚合物的存在使药物在水溶液中的溶出率提高了 7.3 倍。

更新日期:2022-06-26
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