Mass transport in dissolution kinetics. II: Convective diffusion to assess role of viscosity under conditions of gravitational flow.
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).
Shah
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Pharmacy Research, Upjohn Company, Kalamazoo, MI 49001.
Nelson
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D002482:Cellulose / Q000031:analogs & derivatives; D004058:Diffusion; D007700:Kinetics; D012995:Solubility; D014783:Viscosity
D002482:Cellulose; C008079:hydroxypropylcellulose