Preparation and evaluation of theophylline loaded bovine serum albumin microspheres

ABSTRACT

Theophylline-loaded bovine serum albumin [BSA] microspheres were prepared by an emulsion polymerization method using glutaraldehyde as the crosslinking agent. The study was designed to evaluate the effects of different formulation parameters as BSA concentration, surfactant concentration, hydrophilic lipophilic balance [HLB], dispersion medium viscosity and glutaraldehyde concentration on the extent of drug loading, size of microsphere and the in-vitro as "well as the in-vivo release rates of theophylline from such microspheres. Drug polymer ratios of 11, 12, 13, 14, 15 and 16 were investigated. Span 80 was used as a surfactant at different concentrations. Moreover, Different span 80 / tween 80 blend concentrations; 0.5, 1.0 and 2.0% w/v were used to study the effect of HLB. Also different dispersion media; isooctane, light paraffin oil, olive oil and Linseed oil were used for microspheres preparation. In addition, different glutaraldehyde concentrations; 5, 10 and 25% v/v were used. It was found that all micro-spheres were spherical with the mean particle size of 90-180 micro m. The results revealed also that as the concentration of BSA increases, the drug loading is increased. Increasing surfactant concentration and viscosity of the dispersion medium has led to decrease the particle size, while increasing glutaraldehyde concentration nearly had no effect. Furthermore, encapsulation efficiency was found to be directly proprortional to albumin content, surfactant concentration, viscosity of the dispersion medium and glutaraldehyde concentration. Drug release from the prepared microspheres displayed a biphasic pattern characterized by an initial burst, followed by a slower release period, which may be attributed to the presence of theophylline material near to or onto the microspheres surfaces. The bio availability of theophylline from the prepared microspheres was evaluated in rabbits. The prepared microspheres were found to control theophylline release even up to 10 hrs. The peak serum concentrations of such microspheres were within the therapeutic level. The results indicate also that the previoiusly mentioned formulation parameters have a prnounced impact to control the release of the entrapped drug