Roseman T J, Larion L J, Butler S S
J Pharm Sci. 1981 May;70(5):562-6. doi: 10.1002/jps.2600700525.
The in vitro release profiles of the F-series of prostaglandins were determined from a silicone rubber matrix of constant surface area. Silicone rubber was selective toward prostaglandin transport and offers potential as a controlled-release delivery system. Drug release patterns were dependent on the lipophilicity of the prostaglandin molecule. For dinoprost (prostaglandin F2 alpha), the following sequences was observed: methyl ester greater than free acid greater than tromethamine salt. The biologically potent carboprost methyl [(15S)-15-methylprostaglandin F2 alpha methyl ester] was release considerably faster than the methyl ester of the parent dinoprost molecule, while release of the tromethamine salt of the two prostaglandins was similar. Permeability rates of the salts were depressed substantially when compared to their respective C-1 methyl esters. Results from independent membrane transport studies supported the observed dependence of steady-state flux on the chemical structure of the prostaglandin molecule. Plots of the amount released per unit area versus the square root of time were linear except for the initial drug release phase, and the total amount of prostaglandin released increased as the initial loading dose was raised. The data were analyzed according to a physical model describing drug release from inert matrix systems. The observed concentration dependence was consistent with the predictions of the model.
从具有恒定表面积的硅橡胶基质中测定了F系列前列腺素的体外释放曲线。硅橡胶对前列腺素的转运具有选择性，并具有作为控释给药系统的潜力。药物释放模式取决于前列腺素分子的亲脂性。对于地诺前列素（前列腺素F2α），观察到以下顺序：甲酯＞游离酸＞ tromethamine盐。具有生物活性的卡前列甲酯[（15S）-15-甲基前列腺素F2α甲酯]的释放速度明显快于母体地诺前列素分子的甲酯，而两种前列腺素的tromethamine盐的释放情况相似。与它们各自的C-1甲酯相比，盐的渗透率大大降低。独立膜转运研究的结果支持了观察到的稳态通量对前列腺素分子化学结构的依赖性。除了初始药物释放阶段外，每单位面积释放量与时间平方根的关系图呈线性，并且随着初始装载剂量的增加，释放的前列腺素总量也增加。根据描述药物从惰性基质系统释放的物理模型对数据进行了分析。观察到的浓度依赖性与模型的预测一致。
