Department of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany.
Department of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany.
Eur J Pharm Biopharm. 2019 Apr;137:196-208. doi: 10.1016/j.ejpb.2019.02.022. Epub 2019 Feb 28.
The problem of many gastroretentive systems is the mechanistic connection of drug release and gastric retention control. This connection could be successfully separated by formulating hollow tubes via hot-melt extrusion and sealing both tube ends, which led to immediately floating devices. The tube wall consisted of metformin crystals embedded in an inert polymer matrix of Eudragit® RS PO and E PO. Very high drug loadings of up to 80% (w/w) were used without generating a 'burst release'. Sustained release profiles from four to more than twelve hours were achieved by varying the polymer proportions without affecting the floatability. Buoyancy was found to mainly depend on the cylinder design, i.e. the outer to inner diameter ratio. This allowed the polymer/metformin composition to be changed without affecting buoyancy, i.e. a separation of floatability and release control was achieved. A prediction model was implemented that allowed for the buoyancy force to be determined with high accuracy by selecting a suitable ratio of outer to inner diameter of the modular tube die. Wall thickness and mass normalized surface area were identified as geometric parameters that mainly influenced the release properties. Conclusively, this study offers a highly flexible and rational manufacturing approach for the development of gastroretentive floating drug delivery systems.
许多胃滞留系统的问题在于药物释放和胃滞留控制的机械连接。通过热熔挤出并密封管两端来形成空心管，可以成功地将这种连接分离，从而形成立即漂浮的装置。管壁由嵌入惰性聚合物基质（Eudragit® RS PO 和 E PO）中的二甲双胍晶体组成。使用高达 80%（w/w）的非常高的药物载药量，而不会产生“突释”。通过改变聚合物比例，可以实现从四到十二个多小时的持续释放曲线，而不会影响漂浮性。浮力主要取决于圆筒设计，即外直径与内直径的比值。这允许在不影响浮力的情况下改变聚合物/二甲双胍的组成，即实现了漂浮性和释放控制的分离。实施了一种预测模型，通过选择合适的模块管模具的外直径与内直径的比值，可以高精度地确定浮力。壁厚度和质量归一化表面积被确定为主要影响释放性能的几何参数。总之，本研究为胃滞留漂浮药物递送系统的开发提供了一种高度灵活和合理的制造方法。
