Influence of sterilization processes on poly(epsilon-caprolactone) nanospheres.

Polymeric vectors and especially poly(epsilon-caprolactone) nanoparticles have already shown promising results in the optimization of the ophthalmic bioavailability of drugs. Any formulation instilled in the eye must be sterile, and preferentially isotonic. Poly(epsilon-caprolactone) nanospheres were thus formulated with Synperonic PE/F68, Synperonic PE/F127, or Cremophor RH40. A tonicity agent, a preservative and, in some cases, a viscosifiant were then added. The pH was finally adjusted to pH 4 or buffered to pH 7. Different sterilization processes were studied to investigate their influence on the physicochemical characteristics of vectors. Autoclaving did not induce any modification on polymer molecular weight or Synperonic nanospheres diameter, but catalysed some reactions with surfactants and tonicity agents. This method could thus be used if the nanosphere excipients are chosen with care. gamma radiation induced preservative degradation and viscosifiant depolymerization. A cross-linking of poly(epsilon-caprolactone) chains was observed, as reflected by a sharp increase of its molecular weight. However, no variation of the mean particle size was detected. Finally, sterile filtration was the only process which ensured the conservation of physicochemical integrity of nanospheres. This process was successfully applied on non-viscosified vectors with a sufficiently small diameter.