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用于改善溶出度的非诺贝特与共处理介孔二氧化硅固体分散体的口腔崩解片的研制。

Development of Orodispersible Tablets with Solid Dispersions of Fenofibrate and Co-Processed Mesoporous Silica for Improved Dissolution.

作者信息

Baumgartner Ana, Planinšek Odon

机构信息

Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.

出版信息

Pharmaceutics. 2024 Aug 12;16(8):1060. doi: 10.3390/pharmaceutics16081060.

Abstract

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further.

摘要

水溶性差是开发适合患者口服的固体剂型时面临的一项重要挑战。本研究旨在制备含有难溶性药物非诺贝特固体分散体以及由介孔二氧化硅和异麦芽酮糖醇组成的共处理辅料的口腔崩解片。这种共处理辅料是在之前的一项研究中开发出来的,与纯二氧化硅相比,它具有更好的流动性和压缩性能,同时保持了较高的药物吸附比表面积。采用旋转蒸发法制备了含有不同量非诺贝特的固体分散体,并对其固态性质和药物释放情况进行了评估。含有30%非诺贝特的固体分散体没有结晶迹象,溶出速率显著提高,使其成为制备口腔崩解片的最佳样品。目标是在达到与未压缩固体分散体相似的药物释放曲线的同时,使用最少的额外辅料生产片剂。压制制剂在崩解时间方面符合口腔崩解片的要求,最佳制剂的药物释放情况接近未压缩固体分散体的曲线。未来的研究应集中在缩短崩解时间和减小片剂尺寸上,以进一步提高患者的接受度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9938/11359594/68ffc5d10247/pharmaceutics-16-01060-g001.jpg

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