Stability of poly (ε caprolacton) nanospheres in sterile aqueous media

Abstract

Polyester nanoparticles have shown promising results in the ophthalmic area for optimization of the bioavailability of drugs. However, polyesters can undergo hydrolysis during storage in aqueous media and their degradation can be enhanced by micro-organisms. Poly (ε caprolacton) (PEC) nanospheres were formulated for an ophthalmic application, i.e. sterile, isotonic and containing a preservative. Their physical and chemical stabilities were studied during a 6-month storage at 25 and 40°C. The influence of temperature, surfactant, viscosifiant addition, and buffered or non-buffered pH was evaluated. The physical stability of nanospheres was followed by the study of visual appearance and mean particle size. The pH and tonicity of the suspensions, and the molecular weight and crystallinity of PEC were additionally analyzed to evaluate their chemical stability. The influence of surfactants was observed only on the nanosphere physical stability. Better results were obtained with Pluronic F127. The degradation of PEC was especially affected by pH and temperature. At 25°C and pH 7, the variation of polymer molecular weight was negligible. At 40°C, the hydrolysis rate increased with a loss of 50% of the initial molecular weight after 6 months in pH 7 buffer, and 60% in non-buffered pH 7 medium. Finally, the mean particle size of all nanospheres remained unchanged throughout this study.