Mwila Chiluba, Walker Roderick B
Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown 6140, South Africa.
School of Health Sciences, Department of Pharmacy, University of Zambia, Lusaka 10101, Zambia.
Pharmaceutics. 2020 Mar 5;12(3):234. doi: 10.3390/pharmaceutics12030234.
The degradation of rifampicin (RIF) in an acidic medium to form 3-formyl rifamycin SV, a poorly absorbed compound, is accelerated in the presence of isoniazid, contributing to the poor bioavailability of rifampicin. This manuscript presents a novel approach in which isoniazid is formulated into gastric-resistant sustained-release microspheres and RIF into microporous floating sustained-release microspheres to reduce the potential for interaction between RIF and isoniazid (INH) in an acidic environment. Hydroxypropyl methylcellulose acetate succinate and Eudragit L100 polymers were used for the manufacture of isoniazid-loaded gastric-resistant sustained-release microspheres using an o/o solvent emulsification evaporation approach. Microporous floating sustained-release microspheres for the delivery of rifampicin in the stomach were manufactured using emulsification and a diffusion/evaporation process. The design of experiments was used to evaluate the impact of input variables on predefined responses or quality attributes of the microspheres. The percent degradation of rifampicin following 12 h dissolution testing in 0.1 M HCl pH 1.2 in the presence of isoniazid gastric-resistant sustained-release microspheres was only 4.44%. These results indicate that the degradation of rifampicin in the presence of isoniazid in acidic media can be reduced by encapsulation of both active pharmaceutical ingredients to ensure release in different segments of the gastrointestinal tract, potentially improving the bioavailability of rifampicin.
利福平（RIF）在酸性介质中降解生成难以吸收的3-甲酰基利福霉素SV，在异烟肼存在的情况下，这种降解会加速，这导致了利福平生物利用度不佳。本论文提出了一种新方法，即将异烟肼制成耐胃酸的缓释微球，将利福平制成微孔漂浮缓释微球，以降低酸性环境中利福平和异烟肼（INH）之间相互作用的可能性。使用醋酸羟丙甲纤维素琥珀酸酯和丙烯酸树脂L100聚合物，采用油/油溶剂乳化蒸发法制备了载异烟肼的耐胃酸缓释微球。采用乳化和扩散/蒸发工艺制备了用于在胃中递送利福平的微孔漂浮缓释微球。实验设计用于评估输入变量对微球预定义响应或质量属性的影响。在存在异烟肼耐胃酸缓释微球的情况下，利福平在0.1 M HCl（pH 1.2）中进行12小时溶出试验后的降解率仅为4.44%。这些结果表明，通过将两种活性药物成分包封，可减少酸性介质中异烟肼存在下利福平的降解，确保在胃肠道不同部位释放，这可能会提高利福平的生物利用度。
