A solvent partition technique for the microencapsulation of hydrocortisone-polylactic acid has been developed for the preparation of microcapsules of controlled particle size distribution and drug loading. The method involves continuous injection of a drug-polymer solution with a syringe infusion pump into flowing mineral oil where microcapsules are formed as the solvent of the drug-polymer is partitioned into the mineral oil. Using preselected syringe needle size and mechanical control of the mineral oil flow rate at the needle tip, microcapsules of consistent particle sizes and desired drug loadings were prepared. Microcapsules of different internal structures were also prepared by varying the solvent system for the drug-polymer preparation. Dissolution studies showed that at the same drug loading, the rate of the percentage drug release increased with decreasing particle size, and that at similar particle size distributions, the rate increased with increasing drug loading. These results indicate that both the particle size distribution, and the drug loading must be controlled in a microencapsulation process to produce microcapsules of controlled drug release rate.
Polylactic acid microcapsules of similar particle size distribution containing various drug loadings of hydrocortisone were prepared. The microcapsules, which contained randomly dispensed drug particles, showed a dissolution pattern which consists of a fast first-stage and a slow second-stage drug release. Our studies showed that the kinetics of drug release from the microcapsules can be adequately described by a spherical matrix model based on a flux mechanism involving the diffusion of dissolved drug at the penetrating front of the dissolution medium. Drug loading played an important role in the control of drug release rate. An empirical relationship between drug loading and drug diffusibility through the polymeric matrix was developed and showed that the rate of drug release increased exponentially with the increase in drug loading. The microcapsules were further shown to exhibit increased rate of drug release in dissolution medium containing either cetylpyridium chloride or aerosol OT. The effect of the surfactants was attributed to surface tension lowering and improved wetting of the microcapsule particles.
Polylactic acid microcapsules containing randomly distributed hydrocortisone particles were prepared. The rate of release of hydrocortisone from the microcapsules in pH 7.4 phosphate buffer was found to be largely increased by the presence of polysorbate 80, cetylpyridinium chloride, or aerosol OT in the dissolution medium. The surfactant effect was attributed to the ability of the surface active agent to improve solvent penetration into the microcapsules by lowering the surface tension at the solid-liquid interface. The effect of the cationic surfactant, cetylpyridinium chloride on the rate of drug release is similar in magnitude to that of the nonionic surfactant, polysorbate 80. In these systems, the rate of drug release from the microcapsules was found to be linearly related to the surface tension of the dissolution medium in the range of 40-60 dyn/cm (x 10(-3) N/m). In the same surface tension range, the effect of aerosol OT on rate increase was found to be much less than those of the cationic and nonionic surfactants. This suggests that the anionic surfactant is not well adsorbed at the interface due to the negative charge characteristics of the surface of the polylactic acid microcapsules. However, at nearly the critical micelle concentration of aerosol OT, where the corresponding surface tension is much lower than those of the cationic and nonionic surfactants, the microcapsules exhibited the highest rate of drug release.
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