INFLUENCE OF STERILIZATION PROCESSES ON POLY(EPSILON-CAPROLACTONE) NANOSPHERES

Polymeric vectors and especially poly(epsilon-caprolactone) nanopartic les have already shown promising results in the optimization of the op hthalmic bioavailability of drugs. Any formulation instilled in the ey e must be sterile, and preferentially isotonic. Poly(epsilon-caprolact one) nanospheres were thus formulated with Synperonic PE/F68, Synperon ic PE/F127, or Cremophor RH40. A tonicity agent, a preservative and, i n some cases, a viscosifiant were then added. The pH was finally adjus ted to pH 4 or buffered to pH 7. Different sterilization processes wer e studied to investigate their influence on the physicochemical charac teristics of vectors. Autoclaving did not induce any modification on p olymer molecular weight or Synperonic nanospheres diameter, but cataly sed some reactions with surfactants and tonicity agents. This method c ould thus be used if the nanosphere excipients are chosen with care. g amma radiation induced preservative degradation and viscosifiant depol ymerization. A cross-linking of poly(epsilon-caprolactone) chains was observed, as reflected by a sharp increase of its molecular weight. Ho wever, no Variation of the mean particle size was detected. Finally, s terile filtration was the only process which ensured the conservation of physicochemical integrity of nanospheres. This process was successf ully applied on non-viscosified vectors with a sufficiently small diam eter. (C) 1997 Elsevier Science Limited. All rights reserved.