These studies were designed to test the hypothesis that cross-linked chitosan will retard the release of chlorpheniramine maleate from an ion-exchange resin.; The microencapsulation method which utilized the emulsion solvent evaporation technique produce samples with diameters that were suitable for suspensions. A combination of safflower oil and Span 80 produced the best chitosan microspheres at speeds under 500 RPM and at room temperature. The use of acetone as a carrier for the introduction of glutaraldehyde into chitosan/oil proved to be advantageous to the microencapsulation processes. The cross-linking reaction occurred instantaneously and proceeded until either the available cross-linking sites or the glutaraldehyde were depleted. The resulting spheres contain multiple particles embedded in a cross-linked chitosan matrix; these are referred to here as microspheres although this differs from other microsphere definition.; An assay was developed to estimate the degree of cross-linking in chitosan microspheres. Following the autoclaved hydrolysis of the cross-linked microspheres in concentrated HCl, the noncross-linked amine moiety was measured fluorometrically by detecting the fluorescence emitted from a compound derived from the complex of uncross-linked primary amine with fluorescamine. There were three possible sources of error that could contribute to the inaccuracy of the results: the degradation of the primary amine, the generation of primary amine from deacetylation of N-acetylated secondary amine; and regeneration of the primary amine from the cleavage of the cross-links between primary amines. These errors were shown to be reduced considerably in highly deacetylated chitosan as compared to the monmers. In spite of these possible errors, the method still can be used to estimate the extent of cross-linking in highly deacetylated chitosan microspheres.; The dissolution behavior of chlorpheniramine maleate from ion-exchange resin embedded in cross-linked chitosan microspheres in simulated gastric fluid was studied using an USP Apparatus IV continuous flow though cell. The results indicated that chitosan was the barrier that slowed the release of the drug; the retardation effect increased with increasing cross-linking. The kinetic studies indicated that a modified equation was required to account for the influence of the apparatus on the dissolution profiles. The analysis based on the proposed equation demonstrated that the release was controlled by particle diffusion; specifically, the diffusion of chlorpheniramine maleate through cross-linked chitosan.
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