Date of Graduation

1987

Document Type

Dissertation/Thesis

Abstract

A solvent partition technique of microencapsulation, utilizing an apparatus designed to provide a continuous injection of a drug-polymer preparation into a flowing mineral oil system, has been developed via the preparation of hydrocortisone-polylactic acid microcapsules. Using this method, microcapsules of controlled particle size distribution and drug loading were prepared with good reproducibility. Dissolution studies further showed that microcapsules having the same drug loading and particle size distribution exhibited the same rate of release. The drug release profiles, obtained in pH 7.4 phosphate buffer at 37 C, showed a biphasic drug release pattern denoting a fast first-stage and a slow second-stage drug release. Several physicochemical parameters including the drug loading, particle size distribution, drug solubility, and solution surface tension have been shown to influence the rate of drug release from the microcapsules. These parameters are consistent with those of a theoretical equation describing the kinetics of drug diffusion through a spherical polymeric matrix. For the microcapsule system, the rate of drug release was found to increase exponentially with increasing drug loading or decreasing particle size. These effects may be attributed to changes in porosity and tortuosity of the system resulted from the changes in drug loading and particle size. The microcapsules were further shown to exhibit increased rate of drug release in dissolution media containing cetylpyridinium chloride, polysorbate 80, and aerosol OT. The results show a direct relationship between rate increase and surface tension lowering at various concentrations of the surfactants, suggesting that the surfactant effect is due to surface tension lowering at the solid-liquid interface and improved solvent penetration into the microcapsules. The effect of the cationic and nonionic surfactants on the rate of drug release was found to be similar in magnitude in the surface tension range of 40-60 dynes/cm, whereas the anionic aerosol OT exhibited a lesser effect in the same surface tension range. However, at nearly the critical micelle concentration of aerosol OT, where the solution surface tension was much lower than those of the cationic and nonionic surfactants, the microcapsules exhibited the highest rate of drug release.

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