Cellulose acetate phthalate has been used to prepare microcapsules of phenacetin as described by Merkle and Speiser (1973). The polymer was dissolved in an aqueous solution containing a stoichiometrically equivalent quantity of Na2HP04. The stirred solution was maintained at 60°C and the drug was added then the coacervating agent, a solution of sodium sulfate at 60°C. Subsequently, the solution was slowly cooled to 20°C, followed by rapid cooling to 5°C. The polymer was rigidized by treatment with a dilute solution of acetic acid. A triangular phase diagram was prepared representing polymer, water and total salt which included the Na2HP04, the solvating agent, and Na2S04, the coacervating agent. It was found that the amount of drug in the microcapsule had no appreciable effect on the particle size distribution of the microcapsule but did influence the release rates of the drug, suggesting that diffusion of the drug through the microcapsule wall is the controlling step. In order to obtain better utilization of the polymer, a technique was developed for the continuous addition of sodium sulfate during cooling of the system to produce microcapsules. The encapsulation process is able to produce microcapsules of varying drug-to-shell ratios by maintaining the polymer concentration and altering the amount of drug used. The rate of drug release increases as the drug content increases. In contrast, all batches of capsules plasticized by washing with a dilute solution of glycerin for a short period showed identical release rates, despite different drug contents; the authors now suggest that the release rate is controlled by dissolution of the drug in the microcapsule.
Another method of preparing microcapsules using the polymer cellulose acetate phthalate-containing pharmaceuticals with low water solubility was described by Milovanovic and Nairn (1986). Solutions were prepared by dissolving the polymer in dilute solutions of Na2HP04 and heating to 60°C. Various quantities of the drug sulfadiazine, polyoxyethylene 20 sor-bitan monooleate and, if necessary, a viscosity agent such as glycerin, Avicel pH 105 or hydroxypropyl methylcellulose were added to the polymer solution. The stirred suspension was added dropwise to the aqueous hardening solution of diluted acetic acid. A suitable viscosity of the solution to suspend the drug was obtained by using a 2.5% cellulose acetate phthalate solution. Addition of the above-mentioned viscosity agents to this solution did not alter the core:coat ratio, the particle size appreciably, or the percentage of drug incorporated, 81-94%, but the disintegration time was decreased when glycerin was used. The size of the microcapsules tended to increase, the core to coat ratio increased, and the disintegration time decreased as the amount of drug incorporated into the microcapsule increased.
Microcapsules of water-insoluble liquids such as vitamin A palmitate have also been prepared using cellulose acetate phthalate (Anon., 1988).
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