Evaluation of Uniform-Sized Microcapsules Using a Vibration-Nozzle Method

Abstract

In order to prepare microcapsules (MC) using polyvinylacetal diethyl-aminoacetate (AEA) gel, we have studied both the unique properties of AEA gel, in which cold-water solution forms a hard gel with exclusion of water at high temperature, and the microencapsulation technique for clarithromycin (CAM), which has an unpleasant taste (1, 2). In our previous paper (3), we described a new uniform-sized microencapsulation machine with a vibration nozzle with 536 holes 100µ in diameter designed 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 various pHs using the method described in the Japanese Pharmacopoeia (12th edition), a test for bitter taste and a test to determine bioavailability (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 dissolution of CAM from syrup at pH6.8. The results of the test for bitter taste showed that the syrup preparations, which were administered to 12 male and female volunteers with 20ml water, masked bitter taste completely during the 60min period following administration of the syrup. The mean area under the serum concentration-time curve (AUCo-24) and the maximum serum concentration (Cmax) for administration of syrup preparations to 6 male volunteers were 5.66 ± 0.73µg·hr/ml and 0.66 ± 0.13µg/ml, respectively. Blood concentration was maintained at a level above the minimum inhibitory concentration for gram-positive bacteria for a period of about 14hr after administration, demonstrating the usefulness of the syrup preparation.