Date of Graduation
A major concern of investigators during the last decade has been the evaluation of the relative therapeutic effectiveness of competitive drug products. The problem of bioavailability is further exaggerated for steroidal drugs formulated as suspensions because of low intrinsic solubility, and the addition of stabilizing ingredients, such as polymers, to the formulations. An in vitro evaluation of the dissolution rate of hydrocortisone alcohol and acetate from constant surface area tablets into dilute polymer solutions was undertaken since dissolution rate is a relevant characteristic concerning therapeutic availability for sparingly soluble drugs. Polymers of varying chemical type and in dilute concentrations, similar to those in pharmaceutical formulations, were used. Independent measurements of equilibrium drug solubility and drug diffusion coefficient were made in aqueous polymer solutions. Viscosity values were determined for each polymer solution. Dissolution rates were measured in a stationary disk, rotating fluid device and in conjunction with the concentration jump technique. Results showed in general that the diffusion coefficient decreases with increasing viscosity, although not in strict adherence to the Stokes-Einstein relationship. Solubility values did not vary significantly in the presence of different polymers. Flux values for hydrocortisone decreased with increasing viscosity attributed to polymer content. Flux is expected to be directly proportional to solubility and this relationship was verified using hydrocortisone alcohol and acetate, which have similar diffusion coefficients but differing solubilities. Experimental flux values compared well with those calculated using classical convective diffusion theory for each polymer tested, suggesting the viscosity effect for the dilute polymer solutions used in this study. A significant finding is that, for the polymers tested, mass transfer into dilute polymer solutions can be evaluated on the basis of bulk viscosity, without consideration of microenvironmental effects or effects attributed to the chemistry of the polymer. This study also demonstrated that the stationary disk, rotating fluid device provides for consistent experimental conditions for studying mass transfer from sparingly soluble substances of pharmaceutical interest.
KHOURY, NAHLA NASSAR, "DISSOLUTION KINETICS OF HYDROCORTISONE INTO POLYMER SOLUTIONS (STEROIDS)." (1985). Graduate Theses, Dissertations, and Problem Reports. 9175.