Hydrolytic degradation of poly(ε-caprolactone) with different end groups and poly(ε-caprolactone-co--Y-butyrolactone): characterization and kinetics of hydrocortisone delivery

Abstract

Asymmetric telechelic alfa-hydroxyl-ω-(carboxylic acid)-poly(ε-caprolactone) (HA-PCL), alfa-hydroxyl-ω-(benzylic ester)-poly(ε-caprolactone) (HBz-PCL), and an asymmetric telechelic copolymer alfa-hydroxyl-ω-(carboxylic acid)-poly(ε-caprolactone-co-Y-butyrolactone) (HA-PCB) were synthesized by ring-opening polymerization of ε-caprolactone (CL). CL and CL/-butyrolactone mixture were used to obtain homopolymers and copolymer respectively at 150°C and 2 hr using ammonium decamolybdate (NH4) [Mo10O34] (Dec) as a catalyst. Water (HA-PCL and HA-PCB) or benzyl alcohol (HBz-PCL) were used as initiators. The three polylactones reached initial molecular weights between 2000 and 3000 Da measured by proton nuclear magnetic resonance (1H-NMR). Compression-molded polylactone caplets were allowed to degrade in 0.5 M aqueous p-toluenesulfonic acid at 37°C and monitored up to 60 days for weight loss behavior. Data showed that the copolymer degraded faster than the PCL homopolymers, and that there was no difference in the weight loss behavior between HA-PCL and HBz-PCL. Caplets of the three polylactones containing 1% (w/w) hydrocortisone were placed in two different buffer systems, pH 5.0 with citrate buffer and pH 7.4 with phosphate buffer at 37°C, and monitored up to 50 days for their release behavior. The release profiles of hydrocortisone presented two stages. The introduction of a second monomer in the polymer chain significantly increased the release rate, the degradation rate for HA-PCB being faster than those for HBz-PCL and HA-PCL. At the pH studied, only slight differences on the liberation profiles were observed. SEM micrographs indicate that hydrolytic degradation occurred mainly by a surface erosion mechanism.