BIOAVAILABILITY OF THEOPHYLLINE FROM GLUTARALDEHYDE CROSS-LINKED CASEIN MICROSPHERES IN RABBITS FOLLOWING ORAL-ADMINISTRATION

Theophylline loaded bovine casein microspheres were prepared by the gl utaraldehyde cross linking of an aqueous alkaline dispersion of the pr otein containing the drug in a non-aqueous dispersion medium. The cros s-linking of the protein droplets was carried out via the organic phas e by the addition of varying quantities of glutaraldehyde- saturated t oluene. In vitro release of the drug was examined in simulated gastric fluid at 37 degrees C from spheres having three different cross-linki ng densities. The bioavailability of theophylline released from the mi crospheres of different cross-linking densities was studied in rabbits following single oral administration. Microspheres with higher cross- linking densities were found to sustain theophylline release even up t o 24 h. The peak serum concentrations of such preparations were well w ithin therapeutic limits. Determinations of in vitro/in vivo correlati on based on the data showed that a fairly good relationship exists bet ween in vitro and in vivo release. The study demonstrated the potentia l of cross-linked milk protein as a matrix for sustained release oral preparations.