Shah A C, Nelson K G
Pharmacy Research, Upjohn Company, Kalamazoo, MI 49001.
J Pharm Sci. 1987 Dec;76(12):910-3. doi: 10.1002/jps.2600761214.
Dissolution kinetics was studied in a laminar flow cell, through which aqueous solutions of increasing viscosity flowed under the force of gravity, in order to help elucidate the mechanism of drug dissolution. The viscosity was varied by addition of either hydroxypropyl cellulose, sucrose, or glycerin. The dissolution data were evaluated quantitatively in terms of a convective diffusion model for dissolution. It was demonstrated that the decrease in dissolution rate of a test compound due to viscosity in the polymer solution occurs primarily because of a decrease in the rate of shear over the dissolving surface. In solutions of sucrose or glycerin, the decrease in dissolution rate due to viscosity results because of a decrease in the diffusivity of the solute in addition to the decreased rate of shear. Also, the model accounts for the increase in solubility in the glycerin solution. Thus, the influence of viscosity on dissolution depends on whether the viscosity-inducing agent primarily affects only the flow properties of the liquid, or whether it affects diffusivity (i.e., a "micro" viscosity effect, in addition to the flow properties).
在层流流动池内研究了溶出动力学,为了有助于阐明药物溶出机制,粘度不断增加的水溶液在重力作用下流经该流动池。通过添加羟丙基纤维素、蔗糖或甘油来改变粘度。根据溶出的对流扩散模型对溶出数据进行了定量评估。结果表明,聚合物溶液中由于粘度导致的受试化合物溶出速率降低主要是因为溶解表面的剪切速率降低。在蔗糖或甘油溶液中,除了剪切速率降低外,由于溶质扩散系数降低,粘度导致溶出速率降低。此外,该模型解释了甘油溶液中溶解度的增加。因此,粘度对溶出的影响取决于粘度诱导剂主要是仅影响液体的流动性质,还是影响扩散系数(即除流动性质外的“微观”粘度效应)。