摘要
This study aimed to develop a new suppository containing the complex of active pharmaceutical ingredient-ionic liquid (API-IL) and metal organic framework. As two famous drugs with anti-virus activities for the combination therapy of COVID-19, mefloquine (MQ) hydrochloride and artesunate (Art) were combined and then transformed to API-ILs to enhance therapeutic effects. The synthesized [MQ][Art] was characterized using melting point tests, Fourier transform infrared spectrum (FT-IR), proton nuclear magnetic resonance ( 1 H NMR), and mass spectroscopy (MS). Furthermore, [MQ][Art] exhibited improved water solubility, stability and pH values, which promoted treatment effectiveness while minimizing intestinal irritation during administration. Subsequently, [MQ][Art] was incorporated into Zeolitic imidazolate framework-8 (ZIF-8) to further enhance stability and achieve a controlled release effect. Combined with computational studies on interactive energy between ZIF-8 and API-IL, comprehensive characterizations confirmed the successful incorporation of [MQ][Art] on ZIF-8. The preparation method of suppositories was then investigated; among the 9 tested suppository bases, poloxamer-based suppositories demonstrated uniform quality with suitable hardness and melting time while also exhibiting a controlled release effect on [MQ][Art]. After 10 h of cumulative release rate testing reached 90 %. Finally, the poloxamer-based suppository containing [MQ][Art]@ZIF-8 showed good quality uniformity with an average drug content of 11.4 mg per suppository and an average displacement value of 2.59. Besides that, the in vivo release process was detected to demonstrate the effectiveness of the developed system. In conclusion, the combination of API-ILs with ZIF-8 in suppositories designed for COVID-19 treatment enhances therapy effectiveness by improving solubility and stability while also providing controlled release effects on MQ and Art.
危险品化学品经营许可证（带存储）