Addicks W J, Flynn G L, Weiner N, Chiang C M
College of Pharmacy, University of Michigan, Ann Arbor 48109.
Pharm Res. 1988 Jun;5(6):377-82. doi: 10.1023/a:1015963728917.
There are presently no standards for in vitro research dealing with the release and delivery of drugs from semisolid dosage forms, largely because of inherent experimental difficulties. Among the problems, it has proven difficult to apply dosage forms to membranes mounted in in vitro diffusion cells in facsimile to the manner in which the dosage forms are applied clinically. In the present studies, methodology has been developed which allows films with thicknesses approaching clinical dimensions to be spread evenly over silicone rubber membranes. Using methyl p-aminobenzoate as a test permeant and gelled water and water/propylene glycol solvent systems as test vehicles, it has proven possible to spread films as thin as 75 microns, yielding highly reproducible delivery profiles. Using this application technique, it has been shown how the diffusive clearance of drug from films of fixed composition placed over a resistant membrane is dependent on the thickness of application. For a given medium and thickness of application, when the vehicle composition is enriched in propylene glycol, partitioning into the membrane is suppressed, resulting in a lessening of the absolute rate of delivery and, consequently, a prolongation of the period over which drug is released. Increasing the membrane's resistance, i.e., increasing the membrane's thickness, likewise slows down the absolute delivery rate, extending the effective period of total clearance of drug from the applied film.
目前尚无针对半固体制剂药物释放和递送的体外研究标准，这主要是由于存在固有的实验困难。在这些问题中，已证明难以将剂型以临床应用的方式准确地应用于安装在体外扩散池中 的膜上。在本研究中，已开发出一种方法，该方法可使厚度接近临床尺寸的薄膜均匀地铺展在硅橡胶膜上。使用对氨基苯甲酸甲酯作为测试渗透物，凝胶水和水/丙二醇溶剂体系作为测试载体，已证明可以铺展薄至75微米的薄膜，从而产生高度可重复的递送曲线。使用这种应用技术，已表明固定组成的薄膜置于抗性膜上时药物的扩散清除率如何取决于铺展的厚度。对于给定的介质和铺展厚度，当载体组成中丙二醇含量增加时，药物在膜中的分配受到抑制，导致绝对递送速率降低，从而延长了药物释放的时间。增加膜的抗性，即增加膜的厚度，同样会减慢绝对递送速率，延长药物从应用薄膜中完全清除的有效时间。
