Donbrow M, Friedman M
J Pharm Pharmacol. 1975 Sep;27(9):633-46. doi: 10.1111/j.2042-7158.1975.tb09525.x.
Permeability constants of salicylic acid, caffeine and benzoic acid have been measured at 37 degrees for heterogeneous films of ethyl cellulose containing up to 50% PEG 4000, the latter component undergoing leaching out. For the first two compounds, steady state constants were independent of film thickness and solute concentration but increased linearly and sharply with PEG content and were reproducible. The films were impermeable to NaOH and permeation rates were independent of receiver compartment pH. Solubility coefficients and diffusion coefficients of the substances in the films were measured using sorption and/or time lag methods and were low as compared with polyethylene films. High solubility seemed to be associated with the presence of a free activated hydrogen, shown by sorption studies on other substances. From the evidence, it appeared that mass transfer was controlled by the solubility diffusion process in the ethyl cellulose of the membranes with all three substances. Enhancement of permeability by PEG thus seemed due to increased porosity, equivalent to reduction in the effective thickness of the matrix, which nevertheless retained its barrier properties. Enhancement coefficients calculated from the slopes of PEG concentration plots may be useful for predicting the increased mass transfer of drugs through such membranes and could enable the porosity and thickness factors to be balanced against each other for formulation of coated products.
已在37摄氏度下测量了水杨酸、咖啡因和苯甲酸在含有高达50%聚乙二醇4000（PEG 4000）的乙基纤维素非均相膜中的渗透常数，后一种成分会被浸出。对于前两种化合物，稳态常数与膜厚度和溶质浓度无关，但随着PEG含量的增加呈线性急剧增加，且具有可重复性。该膜对氢氧化钠不可渗透，渗透速率与接收室的pH值无关。使用吸附和/或时间滞后方法测量了这些物质在膜中的溶解度系数和扩散系数，与聚乙烯膜相比，这些系数较低。高溶解度似乎与游离活化氢的存在有关，对其他物质的吸附研究表明了这一点。从证据来看，似乎所有这三种物质的传质都受膜中乙基纤维素的溶解度扩散过程控制。因此，PEG对渗透性的增强似乎是由于孔隙率增加，相当于基质有效厚度的减小，不过它仍保留其屏障性能。根据PEG浓度图的斜率计算出的增强系数可能有助于预测药物通过此类膜的传质增加情况，并且能够使孔隙率和厚度因素相互平衡，以用于包衣产品的配方设计。
