Microspheres of Human Serum Albumin with Barbiturates: Effect of Drug Partition Coefficient on Preparation and Drug Release

Abstract Human serum albumin microspheres were prepared with a series of barbiturates by the thermal denaturation method. The barbiturates were of similar general physicochemical properties but different partition coefficients. The total drug content of microspheres was dependent on the partition coefficient, and an increase in the partition coefficient caused a decrease in the drug content of finished microspheres due to drug migration to the outer organic phase during preparation. The ensemble drug release from microspheres was followed by the paddle method and by potentiometric titration with a pH-stat. Nonlinear regression analysis showed the best fit for the spherical Higuchi equation, especially first-order kinetics (bi-phasic). The drug partition coefficient affected the release in such a way that drugs with higher partition coefficients were released faster and to a greater extent than those with lower coefficients.