Adi-Dako Ofosua, Ofori-Kwakye Kwabena, Boakye-Gyasi Mariam El, Oppong Bekoe Samuel, Okyem Samuel
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
School of Pharmacy, University of Ghana, Legon, Ghana.
J Drug Deliv. 2017;2017:8284025. doi: 10.1155/2017/8284025. Epub 2017 Dec 24.
This study evaluated the potential of cocoa pod husk (CPH) pectin as a carrier for chronodelivery of hydrocortisone intended for adrenal insufficiency. FTIR studies found no drug-CPH pectin interactions, and chemometric analysis showed that pure hydrocortisone bears closer similarity to hydrocortisone in hot water soluble pectin (HWSP) than hydrocortisone in citric acid soluble pectin (CASP). CPH pectin-based hydrocortisone matrix tablets (~300 mg) were prepared by direct compression and wet granulation techniques, and the tablet cores were film-coated with a 15% HPMC formulation for timed release, followed by a 12.5% Eudragit® S100 formulation for acid resistance. drug release studies of the uncoated and coated matrix tablets in simulated gastrointestinal conditions showed that wet granulation tablets exhibit greater retardation of drug release in aqueous medium than directly compressed tablets. CASP showed greater suppression of drug release in aqueous medium than HWSP. Wet granulation HWSP-based matrix tablets coated to a final coat weight gain of ~25% w/w were optimized for chronodelivery of hydrocortisone in the colon. The optimized tablets exhibited a lag phase of ~6 h followed by accelerated drug release in the colonic region and have potential to control night time cortisol levels in patients with adrenal insufficiency.
本研究评估了可可豆荚壳(CPH)果胶作为氢化可的松用于肾上腺皮质功能不全的时间控释载体的潜力。傅里叶变换红外光谱(FTIR)研究未发现药物与CPH果胶之间的相互作用,化学计量学分析表明,与柠檬酸可溶性果胶(CASP)中的氢化可的松相比,纯氢化可的松与热水可溶性果胶(HWSP)中的氢化可的松更为相似。采用直接压片和湿法制粒技术制备了CPH果胶基氢化可的松基质片(约300mg),片芯用15%羟丙基甲基纤维素(HPMC)制剂进行薄膜包衣以实现定时释放,随后用12.5%聚丙烯酸树脂S100(Eudragit® S100)制剂进行耐酸包衣。在模拟胃肠道条件下对未包衣和包衣基质片进行的药物释放研究表明,湿法制粒片在水性介质中的药物释放延迟比直接压片更大。CASP在水性介质中对药物释放的抑制作用比HWSP更大。对最终包衣增重约25%(w/w)的基于HWSP的湿法制粒基质片进行了优化,以实现氢化可的松在结肠中的时间控释。优化后的片剂表现出约6小时的滞后阶段,随后在结肠区域药物加速释放,并且有潜力控制肾上腺皮质功能不全患者夜间的皮质醇水平。