Department of Drug Form Technology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Department of Drug Form Technology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland; Institute of Pharmacy, University of Innsbruck, Innrain 52c, 6020 Innsbruck, Austria.
Int J Pharm. 2023 Oct 15;645:123403. doi: 10.1016/j.ijpharm.2023.123403. Epub 2023 Sep 14.
Encapsulation of molecules into mesoporous silica carriers continues to attract considerable interest in the area of drug delivery and crystal engineering. Here, MCM-41, SBA-15 and MCF silica matrices were used to encapsulate fluconazole (FLU), a pharmaceutically relevant molecule with known conformational flexibility, using the melting method. The composites have been characterized using H, C and F NMR spectroscopy, nitrogen adsorption, PXRD and thermal analysis (DSC, TGA). Drug loading up to 50 wt% allowed us to probe the crystallization process and to detect different local environments of confined FLU molecules. F NMR spectroscopy enabled us to detect the gradual pore filling of silica with FLU and differentiate the amorphous domains and surface species. The use of the complementary structural and thermal techniques enabled us to monitor crystallization of the metastable FLU form II in MCF. Using H and F NMR spectroscopy we observed pore-size dependent reversible dehydration/hydration behaviour in the MCM and SBA composites. As water content has considerable importance in understanding of physicochemical stability and shelf-life of pharmaceutical formulations, experimental evidence of the effect of API-water-carrier interactions on the API adsorption mechanism on silica surface is highlighted.
将分子包封到介孔硅载体中在药物输送和晶体工程领域仍然引起了相当大的兴趣。在这里，使用 MCM-41、SBA-15 和 MCF 硅基质，通过熔融法将具有已知构象灵活性的药物相关分子氟康唑（FLU）包封起来。使用 H、C 和 F NMR 光谱、氮吸附、PXRD 和热分析（DSC、TGA）对复合材料进行了表征。高达 50wt%的载药量允许我们探测结晶过程并检测受限 FLU 分子的不同局部环境。F NMR 光谱使我们能够检测到 FLU 逐渐填充硅孔并区分无定形域和表面物种。互补的结构和热技术的使用使我们能够监测 MCF 中亚稳形式 II 的 FLU 结晶。通过使用 H 和 F NMR 光谱，我们观察到在 MCM 和 SBA 复合材料中孔径依赖性的可逆脱水/水合行为。由于水含量对理解药物制剂的物理化学稳定性和保质期具有重要意义，因此强调了 API-水-载体相互作用对 API 在硅表面上吸附机制的影响的实验证据。
