EVALUATION OF UNIFORM-SIZED MICROCAPSULES USING A VIBRATION-NOZZLE METHOD

In order to prepare microcapsules (MC) using polyvinylacetal diethylam inoacetate (AEA) gel, we have studied both the unique properties of AE A gel, in which cold-water solution forms a hard gel with exclusion of water at high temperature, and the microencapsulation technique for c larithromycin (CAM), which has an unpleasant taste (1, 2). In our prev ious paper (3), we described a new uniform-sized microencapsulation ma chine with a vibration nozzle with 536 holes 100 mu m in diameter desi gned for precise regulation of dissolution of CAM from MC. In order to evaluate the MC thus obtained, we prepared syrups (without water) by adding sweetening agents to MC, and conducted a dissolution test at va rious pHs using the method described in the Japanese Pharmacopoeia (12 th edition), a test for bitter taste and a test to determine bioavaila bility (BA) in human subjects. At pHs below 4.0, 100% of CAM in MC was dissolved from the syrup within 5min. However, there was little disso lution of CAM from syrup at pH6.8. The results of the test for bitter taste showed that the syrup preparations, which were administered to 1 2 male and female volunteers with 20ml water, masked bitter taste comp letely during the 60min period following administration of the syrup. The mean area under the serum concentration-time curve (AUC0-24) and t he maximum serum concentration (Cmax) for administration of syrup prep arations to 6 male volunteers were 5.66 +/- 0.73 mu g.hr/ml and 0.66 /- 0.13 mu g/ml, respectively. Blood concentration was maintained at a level above the minimum inhibitory concentration for grampositive bac teria for a period of about 14hr after administration, demonstrating t he usefulness of the syrup preparation.