Characterization and in vitro degradation of salicylate-derived poly(anhydride-ester microspheres)

Abstract

The aim of this study was to investigate how glass transition temperature (T_g) influenced polymer microsphere formation and degradation of three chemically, similar novel salicylatebased poly(anhydride-esters): poly[1,6-bis(o-carboxyphenoxy)hexanoate] (CPH), T_g = 59°C; poly[1,8-bis(o-carboxyphenoxy)octanoate] (CPO), T_g = 30°C; and poly[1,10-bis(ocarboxyphenoxy) decanoate] (CPD), T_g = 27°C. Microspheres of these polymers were prepared using a modified oil-in-water solvent evaporation method and processed by either resuspension or washed by centrifugation. The morphology of the microspheres determined by scanning electron microscopy (SEM) revealed that an extra washing step appears to increase aggregation as the T_g decreases; whereas only limited aggregation occurred in the polymer with the lowest T_g, CPD, in those not washed by centrifugation. Residual polyvinyl alcohol apparently affected the drug release rates from the microspheres by a stabilization process that produced an 8 h lag time and a 5% decrease in the amount of drug released over a 7 day period compared to microspheres washed free of PVA. These results demonstrate that salicylate-based poly(anhydride-esters) with sufficiently high T_gs, can be processed into microspheres that release salicylate over a time period amenable for drug delivery applications.

Key Words: :

• Microspheres
• salicylic acid
• polyanhydrides
• controlled release