Bioavailability of theophylline from glutaraldehyde cross-linked casein microspheres in rabbits following oral administration

Abstract

Theophylline-loaded bovine casein microspheres were prepared by the glutaraldehyde cross-linking of an aqueous alkaline dispersion of the protein containing the drug in a non-aqueous dispersion medium. The cross-linking of the protein droplets was carried out via the organic phase by the addition of varying quantities of glutaraldehyde- saturated toluene. In vitro release of the drug was examined in simulated gastric fluid at 37°C from spheres having three different cross-linking densities. The bioavailability of theophylline released from the microspheres 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 to 24 h. The peak serum concentrations of such preparations were well within therapeutic limits. Determinations of in vitro/in vivo correlation based on the data showed that a fairly good relationship exists between in vitro and in vivo release. The study demonstrated the potential of cross-linked milk protein as a matrix for sustained release oral preparations.