Polyanhydrides as Delivery Systems

Abstract

Poly[(carboxyphenoxy) butane : sebacic acid] ( P(CPB:SA) ) 20:80 and 50:50 microspheres containing 10% w/w theoretical loading bovine serum albumin (BSA) were prepared by solvent evaporation / double emulsion, spray drying and solvent extraction / oil-in-oil techniques. This paper describes the characterisation of the microparticles obtained (morphology, particle size, drug content, in vitro drug release behaviour) and a comparison of the results (drug loading, drug release, size of the microspheres) obtained from different techniques used. The microspheres containing protein were general spherical, with diameters around 10 µm for double emulsion, around 2 µm for spray drying, and 50 µm for solvent extraction / oil-in-oil method. Jn vitro release of the protein into 0.1 M phosphate buffer at 37 °C from microspheres prepared by the three techniques showed that the BSA release rate from the microspheres prepared by solvent extraction / oil-in-oil technique was much quicker with large initial burst compared to the release from the solvent-evaporated and spray dried microspheres. The BSA release profiles for microspheres prepared by double emulsion method did not correlate with the degradation of the microspheres. After 24 hours degradation, most of the anhydride linkage was cleaved, while only around 10 % of the protein was released in six weeks in vitro, but in pH10 Na2CO3 / NaHCO3 buffer nearly 70% of protein was released in two weeks. The IR spectra of the microspheres prepared by different methods, showed that some parts of the polymer began to degrade during the process of preparation, especial for microspheres prepared by spray drying and oil-in-oil methods.