Design of an injectable system based on bioerodible polyanhydride microspheres for sustained drug delivery.

The fabrication, morphological characterization, and drug release kinetics from microspheres of three bioerodible polyanhydrides, poly[1,6-bis(p-carboxyphenoxy)hexane] (poly(CPH)), poly(sebacic anhydride) (poly(SA)), and the copolymer poly(CPH-co-SA) 50:50 (CPH:SA 50:50) is reported. The fabrication technique yields microspheres with different morphologies for each of the three polymers studied, ranging from very smooth exterior surfaces for poly(CPH) to coarse surface roughness with large pores for poly(SA). Release profiles for the model drug, p-nitroaniline are also different for each polymer. The release profile from poly(CPH) has a large initial burst and shows little additional release after 2 days. The release from poly(SA) is nearly zero-order and lasts for about 8 days. The release profile from CPH:SA 50:50 shows a relatively small burst and then exhibits zero-order release for about I month. The different release profiles are attributed to both polymer erosion rates and drug distribution characteristics of the microspheres. Tailored release profiles of a burst followed by zero-order release are obtained by appropriately combining the microspheres. This technique enables independent modulation of both the burst and the zero-order release rate by varying the number of poly(CPH) and poly(SA) microspheres respectively. Additionally, the zero-order release can be extended from about a week to a month by including CPH:SA 50:50 microspheres.