Capsules with prolonged action. III. Release of active ingredients from cast films.

In the preceding paper we described a gelation process and the development of sustained-release soft gelatin capsules containing codeine or theophylline. Applying this process to indomethacin and nifedipine as active ingredients led to insufficient release rates of the products. To investigate this phenomenon two simple membrane models were used, i.e., a cast drug-free membrane composed of different ratios of polyethylene glycol 400 in a matrix of 5% ethylcellulose, 10% sesame oil, and 57 to 69% citric acid triethyl ester and a cast drug-containing membrane with the same excipients. Codeine and indomethacin were able to penetrate drug-free membranes. The amount of drug diffused through the membrane correlates with the solubility data. Theophylline, which is insoluble in the matrix system, does not penetrate through a drug-free matrix. Nifedipine is enriched within the matrix because of its high partition coefficient into the matrix material, and therefore, little release is observed. From a drug-containing matrix, theophylline and nifedipine were released according to Higuchi's equation [J. Pharm. Sci. 52:1145-1149 (1963)], although the absolute amount of nifedipine released is limited because of its high solubility in the membrane material. For codeine and indomethacin there was no linear relationship between the amount of drug released and the square root of time. These results agree with the findings for capsules obtained from the gelation process.