Glutaraldehyde cross-linked bovine casein microspheres as a matrix for the controlled release of theophylline:...

A controlled release dosage form of theophylline in the form of microspheres using the milk protein casein as the matrix is described. Glutaraldehyde cross-linking of an aqueous alkaline solution of the protein containing the drug, dispersed in a mixture of dichloromethane/hexane having ca. 1% of an aliphatic polyurethane as the suspension stabilizer, led to the formation of the drug-loaded microspheres. Drug incorporation efficiency of around 80% could be achieved by the technique. Release profiles of the drug were examined in simulated gastric and intestinal fluids at 37 degrees C. It was observed that the release was diffusion-controlled and followed the Higuchi model. Release characteristics were influenced by the cross-linking density, particle size and the extent of loading. Data obtained indicate that the natural milk protein casein could be used as a matrix for sustained release oral dosage forms.