Kowaluk E A, Roberts M S, Polack A E
J Pharm Sci. 1984 Jan;73(1):43-7. doi: 10.1002/jps.2600730111.
The dynamics of the interaction of clomethiazole edisylate (1) with polyvinyl chloride and cellulose propionate, the main plastics used in the manufacture of infusion bags and sets, was examined. An experimental system in which the plastic was either open or closed to the environment was used to determine the relative contribution of the sorption and permeation processes to loss from solutions of clomethiazole edisylate (I) in contact with the plastic infusion systems. Sorption by the plastic infusion materials accounted for most of the drug loss, while permeation into the external environment accounted for the remainder. The sorption and permeation into and through polyvinyl chloride was temperature dependent. The diffusion coefficient and permeation rate constant both increased with temperature, while the polyvinyl chloride-water partition coefficients were independent of temperature. The activation energy for the diffusion in polyvinyl chloride was 13.5 kcal/mol. The permeability of the infusion bag plastic and the evaporation across an unstirred air boundary layer adjacent to the external surface of the plastic both appeared to contribute to the overall diffusional resistance encountered in the permeation process. The plastic-water partition coefficients are independent of initial concentration, suggesting that the concentration-dependent loss of the drug from solutions stored in plastic infusion bags and burets is a result of the greater diffusivity of the drug in the plastic at the higher initial concentrations. Plasticization of the polymers by the drug is indicated by the increase in the diffusivity of the drug in polyvinyl chloride and cellulose propionate, the increase in the rate and extent of sorption of a radiolabeled marker (diazepam) by the plastic, and the decreased stiffness of polyvinyl chloride exposed to higher concentrations of the drug.
研究了乙磺半胱胺（1）与聚氯乙烯和丙酸纤维素（用于制造输液袋和输液器的主要塑料）相互作用的动力学。使用一个塑料对环境开放或封闭的实验系统来确定吸附和渗透过程对与塑料输液系统接触的乙磺半胱胺（I）溶液损失的相对贡献。塑料输液材料的吸附占药物损失的大部分，而向外部环境的渗透占其余部分。进入和通过聚氯乙烯的吸附和渗透与温度有关。扩散系数和渗透速率常数均随温度升高而增加，而聚氯乙烯 - 水分配系数与温度无关。在聚氯乙烯中扩散的活化能为13.5千卡/摩尔。输液袋塑料的渗透性以及穿过与塑料外表面相邻的未搅拌空气边界层的蒸发似乎都对渗透过程中遇到的总扩散阻力有贡献。塑料 - 水分配系数与初始浓度无关，这表明药物从储存在塑料输液袋和滴管中的溶液中浓度依赖性损失是由于药物在较高初始浓度下在塑料中的扩散率更高所致。药物对聚合物的增塑作用表现为药物在聚氯乙烯和丙酸纤维素中的扩散率增加、塑料对放射性标记物（地西泮）的吸附速率和程度增加以及暴露于较高浓度药物的聚氯乙烯硬度降低。
