PREPARATION AND EVALUATION OF THEOPHYLLINE LOADED BOVINE SERUM ALBUMIN MICROSPHERES

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 1:1, 1:2, 1:3, 1:4, 1:5 and 1:6 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 μm. 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 bioavailability 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.