GLUTARALDEHYDE CROSS-LINKED BOVINE CASEIN MICROSPHERES AS A MATRIX FOR THE CONTROLLED-RELEASE OF THEOPHYLLINE - IN-VITRO STUDIES

A controlled release dosage form of theophylline in the form of micros pheres using the milk protein casein as the matrix is described. Gluta raldehyde 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 stabiliz er, led to the formation of the drug-loaded microspheres. Drug incorpo ration efficiency of around 80% could be achieved by the technique. Re lease profiles of the drug were examined in simulated gastric and inte stinal fluids at 37 degrees C. It was observed that the release was di ffusion-controlled and followed the Higuchi model. Release characteris tics were influenced by the cross-linking density, particle size and t he extent of loading. Data obtained indicate that the natural milk pro tein casein could be used as a matrix for sustained release oral dosag e forms.