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.
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机译：在异烟肼存在下，酸性介质中利福平（RIF）的降解形成3-甲酰基利福霉素SV（一种吸收不良的化合物）会加速降解，导致利福平的生物利用度较差。该手稿提出了一种新方法，其中将异烟肼制成耐胃液的缓释微球，将RIF制成微孔漂浮的缓释微球，以减少酸性环境中RIF与异烟肼（INH）相互作用的可能性。羟丙基甲基纤维素乙酸琥珀酸酯和Eudragit L100聚合物用于通过O / O溶剂乳化蒸发方法制造负载异烟肼的耐胃缓释微球。使用乳化和扩散/蒸发工艺制造了用于在胃中递送利福平的微孔漂浮缓释微球。实验的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。在存在异烟肼胃抗性缓释微球的情况下，在0.1 M HCl pH 1.2中进行12小时溶出度试验后，利福平的降解百分率仅为4.44％。这些结果表明，通过包封两种活性药物成分以确保在胃肠道的不同部分释放，可以减少在酸性介质中存在异烟肼的情况下利福平的降解，从而确保利福平的生物利用度。
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