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一种用于测定微溶性药物扩散系数的试管法的评估

Evaluation of a tube method for determining diffusion coefficients for sparingly soluble drugs.

作者信息

Stout P J, Khoury N, Mauger J, Howard S

出版信息

J Pharm Sci. 1986 Jan;75(1):65-7. doi: 10.1002/jps.2600750115.

DOI:10.1002/jps.2600750115
PMID:3485713
Abstract

Evaluation of a non-steady state method using glass tubes for the determination of diffusion coefficients is the purpose of this study. Unlike capillaries, glass tubes accommodate a larger volume of solution, facilitating assay procedures. Tubes are more susceptible to convection than are capillaries, but this effect is anticipated and accounted for in experimental design and data treatment. Glass tubes, 66 or 90 mm in length and 2 mm outer diameter, were siliconized and then filled with aqueous drug solution and placed in a jacketed flask containing gently stirred solvent at 25 degrees C. Diffusion experiments were run from 140 to 168 hours. At the end of this time period, the tubes were removed from the flask, placed in an ultrasonic vibrator for one minute, and their contents assayed spectrophotometrically. Data collected using potassium chloride as the diffusant showed little tube-to-tube variability, demonstrating the precision of the tube method, while diffusion coefficients determined for benzoic acid and p-aminobenzoic acid using the tube method tested the accuracy of the method by comparing reasonably well with values obtained using standard methods such as the rotating disk, free boundary, and membrane cell. Experiments done with either hydrocortisone or sulfisoxazole as the diffusant demonstrated the appropriateness of the tube method for the study of the diffusion of sparingly soluble pharmaceutical solutes.

摘要

本研究旨在评估一种使用玻璃管的非稳态方法来测定扩散系数。与毛细管不同,玻璃管可容纳更大体积的溶液,便于分析程序。与毛细管相比,玻璃管更容易受到对流影响,但在实验设计和数据处理中已考虑到这种影响并加以应对。将长度为66或90毫米、外径为2毫米的玻璃管进行硅化处理,然后装入药物水溶液,置于装有在25℃下轻轻搅拌的溶剂的夹套烧瓶中。扩散实验持续140至168小时。在这段时间结束时,将玻璃管从烧瓶中取出,放入超声振动器中一分钟,然后用分光光度法测定其内容物。以氯化钾作为扩散剂收集的数据显示,不同玻璃管之间的差异很小,证明了玻璃管法的精密度,而使用玻璃管法测定苯甲酸和对氨基苯甲酸的扩散系数时,通过与使用旋转圆盘、自由边界和膜池等标准方法获得的值进行合理比较,检验了该方法 的准确性。以氢化可的松或磺胺异恶唑作为扩散剂进行的实验表明,玻璃管法适用于研究微溶性药物溶质的扩散。

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