PHASE-DIAGRAM STUDIES FOR MICROENCAPSULATION OF PHARMACEUTICALS USING CELLULOSE-ACETATE TRIMELLITATE

Phase diagrams were prepared to indicate the region of microcapsule formation for the following system: cellulose acetate trimellitate, light mineral oil, and the solvent mixture (acetone:ethanol), using chloroform as the hardening agent. The effect of sorbitan monooleate, sorbitan monolaurate, and sorbitan trioleate on the region of the phase diagram for the formation of microcapsules was investigated. The results indicate that microcapsules are readily formed when the polymer concentration is in the 0.5-1.5% range and the solvent concentration is in the 5-10% range. Aggregation of microcapsules was minimized by using lower solvent concentration. Low concentrations of sorbitan monooleate in mineral oil (less-than-or-equal-to 1%) gave products that had smoother coats and more uniform particle size. Surfactants with low hydrophile:lipophile balance produced larger regions on the phase diagram for microencapsulation compared with a surfactant with higher hydrophile:lipophile balance. A mechanism for microencapsulation is described. Tartrazine microcapsules produced using different concentrations of surfactant were tested for dissolution characteristics in both acidic and neutral conditions. Tartrazine-containing microcapsules prepared by using 3% sorbitan monooleate had the lowest release in acidic conditions. The effect of surfactant and formulation concentration on microcapsule size was studied by analyzing the particle size distribution for both blank and tartrazine-containing microcapsules. The smallest microcapsule size was obtained when the sorbitan monooleate concentration was 3%. It appears that there is an upper limit for the surfactant concentration that could be used to achieve successful microencapsulation.