Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Children's Hospital of Nanjing Medical University, Nanjing, China.
AAPS PharmSciTech. 2022 May 10;23(5):141. doi: 10.1208/s12249-022-02261-5.
Due to poor solubility and stability in acid conditions, the gastrointestinal administration of stiripentol (STP) is still a significant challenge. This study aimed to explore the applicability of effervescent tablets compressed from STP-loaded enteric solid dispersions to improve the solubility and stability of the insoluble and acid-labile drug. STP-loaded solid dispersions (STP-SDs) and the effervescent tablets (STP-SD-ETs) were prepared using solvent evaporation and dry granulation technology, respectively, and their formulations were optimized. Then, STP-SDs were characterized regarding solid state, in vitro release, stability, etc. Results showed that enteric amorphous STP-SDs were successfully prepared and significantly improved the solubility and stability of STP. Moreover, compared with STP suspensions, the bioavailability of STP-SD-ETs was as high as 138.71%. Concomitantly, STP-SD-ETs significantly increased the intestinal absorption rate of STP. Overall, the oral preparation encompassing enteric solid dispersion combined with effervescent tablet technology possesses excellent performance in enhancing dissolution, anti-acid hydrolysis stability, and absorption of STP. Our work provides a promising method to improve the delivery of drugs with poor solubility and acid-labile stability.
由于在酸性条件下溶解度和稳定性差，胃肠道给予屈戊乙草醚（STP）仍然是一个重大挑战。本研究旨在探索由载有 STP 的肠溶性固体分散体压缩而成的泡腾片在提高难溶性和酸不稳定药物的溶解度和稳定性方面的适用性。采用溶剂蒸发和干法制粒技术分别制备了载有 STP 的固体分散体（STP-SD）和泡腾片（STP-SD-ET），并对其配方进行了优化。然后，对 STP-SD 进行了固态、体外释放、稳定性等方面的表征。结果表明，成功制备了肠溶性无定形 STP-SD，显著提高了 STP 的溶解度和稳定性。此外，与 STP 混悬剂相比，STP-SD-ET 的生物利用度高达 138.71%。同时，STP-SD-ET 显著提高了 STP 的肠道吸收速率。总的来说，包含肠溶性固体分散体和泡腾片技术的口服制剂在提高 STP 的溶解、抗酸水解稳定性和吸收方面具有优异的性能。我们的工作为提高难溶性和酸不稳定药物的递送提供了一种很有前途的方法。
