Preparation of enteric-coated microcapsules for tableting by spray-drying technique and in vitro simulation of drug release from the tablet in GI tract

Abstract

Improved methods were developed for the preparation of enteric-coated microcapsules for tableting by a spray-drying technique, and the drug release behavior from the tableted microcapsules was investigated using a disintegration apparatus and a new in vitro method of simulating the GI tract. As a model system, ammonium solutions of sulfamethoxazole and cellulose acetate phthalate were spray dried using a centrifugal wheel atomizer at 140 degrees. Additives such as colloidal silica, montmorillonite clay, and talc were included in the formulations for spray drying. The influence of the additives on the particle diameter, density, packing properties, and compressibility of the product and on the release characteristics of the resultant tablet in vitro were investigated. The additives in the formulations greatly improved the flow properties of the spray-dried products, which could be tableted easily. Products from the nonadditive formulations could not be tableted due to their poor flowability. The hardness and disintegration rate of the tablet increased with increasing concentration of additives in the formulations. X-ray analysis and IR spectroscopy confirmed that the crystals of sulfamethoxazole in the spray-dried microcapsules with cellulose acetate phthalate were converted from Form I to Form II. In vitro release characteristics of the tablets were studied using a disintegrator (JP) in buffer solutions (pH 1.2 and 7.5) and distilled water. Enteric action of the spray-dried products was proved by comparison with the original nontreated powders. The additives in the tablet increased the release rate at the initial stage in all dissolution media used. A new in vitro release simulator was devised consisting of a flow-type dissolution container in which the pH of the medium was changed continuously from 1.2 to 7.0 to simulate the pH change of tablets exposed to the GI tract.