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地塞米松结肠靶向给药设计:固体分散体的制剂与体外特性研究

Design of colon-targeted drug delivery of dexamethasone: Formulation and in vitro characterization of solid dispersions.

作者信息

Zaid Alkilani Ahlam, Omar Sara, Nasereddin Jehad, Hamed Rania, Obeidat Rana

机构信息

Department of Pharmacy, Faculty of Pharmacy, Zarqa University, Zarqa, Jordan.

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.

出版信息

Heliyon. 2024 Jul 6;10(14):e34212. doi: 10.1016/j.heliyon.2024.e34212. eCollection 2024 Jul 30.

Abstract

Colon-targeted drug delivery continues to generate increasing attention for its prospects in treating inflammatory bowel disease (IBD). This study aimed to develop and evaluate colon-targeted solid dispersions of dexamethasone (DEX-SDs) in vitro to reduce its systemic exposure. This would ultimately improve the therapeutic efficacy of DEX while minimizing its adverse effects. Different DEX-SDs formulations were prepared utilizing Eudragit S100 (EU S100) and a combination of hydroxypropyl methyl cellulose (HPMC) and EU S100 to tune its drug release profile suitable for colonic delivery. The fabricated formulations were extensively characterized via Attenuated Total Reflectance - Fourier Transform Infrared Spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and polarized light microscopy (PLM). The different characterization techniques strongly suggest preparing solid solution-type solid dispersions of DEX with the other polymers (DEX-SDs). In addition, the in vitro dissolution of DEX-SDs was evaluated using two dissolution media (pH 1.2 and 7.4). The in vitro release of DEX-SDs was low in the acidic media and higher and sustained in the basic medium, leading to the conclusion that the developed DEX-SDs may represent an effective technology can overcome challenges related to poor drug solubility and bioavailability.

摘要

结肠靶向给药因其在治疗炎症性肠病(IBD)方面的前景而持续受到越来越多的关注。本研究旨在开发并体外评估地塞米松结肠靶向固体分散体(DEX-SDs),以降低其全身暴露。这最终将提高地塞米松的治疗效果,同时将其不良反应降至最低。利用尤特奇S100(EU S100)以及羟丙基甲基纤维素(HPMC)与EU S100的组合制备了不同的DEX-SDs制剂,以调整其药物释放曲线使其适合结肠给药。通过衰减全反射-傅里叶变换红外光谱(ATR-FTIR)、差示扫描量热法(DSC)、粉末X射线衍射(PXRD)和偏光显微镜(PLM)对制备的制剂进行了全面表征。不同的表征技术有力地表明制备了地塞米松与其他聚合物的固溶体型固体分散体(DEX-SDs)。此外,使用两种溶出介质(pH 1.2和7.4)评估了DEX-SDs的体外溶出度。DEX-SDs在酸性介质中的体外释放较低,在碱性介质中较高且持续,得出的结论是,所开发的DEX-SDs可能代表一种有效的技术,可克服与药物溶解度和生物利用度差相关的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/554c/11295959/e9ae8ffbaf46/ga1.jpg

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