Chen S X, Lostritto R T
School of Pharmacy, University of Connecticut, Stors 06269, USA.
J Pharm Sci. 1997 Jun;86(6):739-46. doi: 10.1021/js960324e.
The purpose of this study was to develop a new design for transdermal system that provides a nearly constant drug delivery rate for the desired period of time in the absence of a large excess of drug in the donor reservoir. Simultaneous drug diffusion and aqueous binary vehicle evaporation has been investigated as a means of maintaining constant drug delivery from minidose reservoirs. Benzocaine was used as the model drug and water-ethanol mixtures as the binary vehicles. Benzocaine is much more soluble in ethanol than in water. Simultaneous diffusion-evaporation experiments were conducted using the water-ethanol mixture saturated with benzocaine as the minidose-reservoir. The reservoir vehicle was allowed to evaporate through a permselective membrane so as to maintain drug saturation in the vehicle even though the drug mass in the donor reservoir was constantly decreasing. Saturation activity of drug is maintained during donor depletion of drug by the selective loss of alcohol from the donor solvent, which concomitantly lowers the solubility. The superiority of the evaporable binary vehicle over a conventional sealed system was demonstrated by achieving near zero-order drug delivery with minimum drug remaining. A theoretical model was developed to predict drug flux, drug amount delivered, reservoir solvent volume and composition, and drug solubility during the two simultaneous processes of drug release and preferential solvent evaporation. Experimental data are in good agreement with theoretical calculations.
本研究的目的是开发一种新的透皮系统设计，该系统在供体贮库中不存在大量过量药物的情况下，能在所需时间段内提供近乎恒定的药物释放速率。作为从小剂量贮库维持恒定药物释放的一种方法，已对药物的同时扩散和二元水性载体蒸发进行了研究。使用苯佐卡因作为模型药物，水 - 乙醇混合物作为二元载体。苯佐卡因在乙醇中的溶解度比在水中大得多。使用饱和苯佐卡因的水 - 乙醇混合物作为小剂量贮库进行了同时扩散 - 蒸发实验。贮库载体通过渗透选择性膜蒸发，以便即使供体贮库中的药物量不断减少，也能保持载体中的药物饱和。在供体药物耗尽期间，通过供体溶剂中乙醇的选择性损失来维持药物的饱和活性，这同时降低了溶解度。通过以最少的剩余药物实现接近零级的药物释放，证明了可蒸发二元载体相对于传统密封系统的优越性。开发了一个理论模型来预测药物通量、递送的药物量、贮库溶剂体积和组成以及在药物释放和优先溶剂蒸发这两个同时进行的过程中的药物溶解度。实验数据与理论计算结果吻合良好。
