Elementary osmotic pump for indomethacin.

Based on the principles of an elementary osmotic pump, systems were designed to deliver indomethacin in solution at a constant rate, Z, to contain a total amount of drug, Mt, and to deliver 80% of their content at time t80. To allow selection of the optimal delivery rate into the body, three different prototypes were prepared with respective values for Z, Mt, and t80 of: 7 mg/hr, 85 mg, 11 hr; 9 mg/hr, 85 mg, 8 hr; and 12 mg/hr, 85 mg, 6 hr. These systems were found to deliver 70% of each system's contents at zero-order rates. Delivery rates were independent of pH, method of measurement, and stirring rate. In keeping with these results, the systems in the GI tract of dogs delivered at the same rate as in vitro, which qualifies the in vitro test as a bioanalogous method predictive of the in vivo performance of the dosage forms. Preliminary results in normal volunteers yielded similar urinary recoveries, while plasma profiles were different from each other and distinct from those following conventional capsules.