Preparation, characterization and in vitro drug release properties of polytrimethylene carbonate/polyadipic anhydride blend microspheres

Abstract

Polyadipic anhydride (PAA), an aliphatic polyanhydride, and polytrimethylene carbonate (PTMC), an aliphatic polycarbonate, were synthesized via ring opening polymerization of oxepan-2,7-dione and melt-condensation of trimethylene carbonate (1,3 dioxan-2-one), respectively. PTMC-PAA blend microspheres containing different ratios of buprenorphine HCl (2, 5, and 10%) were prepared by an oil-in-oil emulsion solvent removal method. Microspheres with different ratios of PTMC-PAA (85/15, 70/30, and 55/ 45) containing 5% buprenorphine HCl were prepared. Microspheres were spherical with visible cracks and pores on the surface. The average particle size of microspheres was around 200 μm for all microspheres. Drug loading efficiency of PTMC-PAA microspheres (85/15, 70/30, and 55/45) was 97.2, 95.2, and 70.2%, respectively. With the increase in the PTMC ratio, the melting point and the enthalpy of melting were both decreased. The mechanism for drug release from PTMC-PAA blend microspheres were generally a combination of drug diffusion through polymers and biodegradation of the polymers. In first three days, the release from microspheres followed zero order kinetics and was dependent on the PAA content. After three days the drug release from microspheres followed first order kinetics. In conclusion it was demonstrated that buprenorphine HCl release from microspheres could be successfully controlled by using different ratios of PTMC-PAA blends. © 2006 Wiley Periodicals, Inc.