Preparation and in vitro evaluation of chitosan matrices for the colonic controlled release of proteins

Matrices for colonic controlled release of the model protein drug bovine serum albumin (BSA) were prepared by direct compression of chitosan (CH) or chitosan hydrochloride (CHHCl) microspheres containing 4% BSA, without the aid of any other ingredient. The matrices (6 mm diameter, 50 mg weight each) are destined to be filled into enteric coated size 00 capsules and thereby conveyed to the proximal colon. Protein release was studied in vitro using pH 7.4 buffer as the elution medium. Release from microspheres was exceedingly fast, whereas the matrices were able to control release over prolonged periods. In the elution medium both the CH- and the CHHCl-based matrices swelled without disintegrating. The latter matrix type swelled to a much higher degree. Protein release from matrices was diffusion-controlled and independent of external medium hydrodynamics. The time for release of 50 % dose was much shorter for the CHHCl-based than for the CH-based matrix (0.9 vs. 12.0 h), so the latter is more suitable as a controlled-release system for proteins.