Novel technology for the preparation of sterile alginate-poly-l-lysine microcapsules in a bioreactor.

Abstract

The purpose of this study was to develop a method that may be suitable for the commercial manufacture of sterile alginate-polylysine-alginate microcapsules in a bioreactor. A Turbotak atomizing device in conjunction with a Bellco Bioreactor was used to prepare sterile microcapsules. Aseptic procedures were followed using sterilized equipment and materials. Sodium alginate solution was sprayed into calcium chloride solution using the Turbotak, with nitrogen as the atomizing gas. The resultant gelled alginate microcapsules were coated with polylysine and alginate to produce alginate-poly-l-lysine microcapsules. In-process contamination of the atomizing gas and microcapsules was investigated using modified USP sterility tests. Microcapsule size was determined using a light blockage technique (Accusizer) which measures both number and volume weighted mean diameters. The microcapsules prepared passed a modified USP sterility test, and the Bellco Bioreactor was found to minimize the possibilities of environmental contamination and therefore enhanced operator safety. The flow rate of the atomizing gas was determined to significantly alter number and volume weighted mean microcapsule diameters. Statistical analysis indicated that the number weighted mean diameters in conjunction with the volume weighted mean diameters can be used to detect batch-to-batch changes in microcapsule diameters. In conclusion, the modified Bellco Bioreactor offers a novel approach for producing sterile alginate-polylysine microcapsules on a laboratory scale.