Mass transport in dissolution kinetics. I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions.
The quantitative influence of viscosity on dissolution kinetics is assessed under laminar flow conditions by utilizing a convective diffusion model for drug dissolution. Functional dependency of three types of viscosity inducing agents is established with respect to the parameters of fluid flow rate, diffusivity, and solubility. Studies of aqueous solutions of sucrose and of glycerol demonstrate that the decrease in dissolution rate of ethyl p-aminobenzoate is related to the decrease in solute diffusivity in these solutions, whereas the solubility change in the glycerol solutions has an additional independent simultaneous effect. Dissolution in hydroxypropyl cellulose solutions remains constant under fixed fluid flow conditions because of the negligible effect of the polymer upon the drug diffusivity. A change in fluid flow rate, however, alters the dissolution rate and correlates quantitatively with the rate of shear in the convective diffusion model. The interpretation of the effect of viscosity on dissolution kinetics with the convective diffusion model explains these phenomena quantitatively in terms of the fundamental mass transport processes.
Nelson
K G
KG
Pharmacy Research, Upjohn Company, Kalamazoo, MI 49001.
Shah
A C
AC
D002482:Cellulose / Q000031:analogs & derivatives; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D007700:Kinetics; D008962:Models, Theoretical; D012995:Solubility; D014783:Viscosity
D002482:Cellulose; C008079:hydroxypropylcellulose