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

Area of Science:

• Ophthalmic drug delivery
• Nanoparticle formulation
• Polymer science

Background:

• Poly(epsilon-caprolactone) nanoparticles enhance ophthalmic drug bioavailability.
• Ophthalmic formulations require sterility and isotonicity.
• Various surfactants were evaluated for nanosphere formulation.

Purpose of the Study:

• To formulate poly(epsilon-caprolactone) nanospheres with different surfactants.
• To evaluate the impact of sterilization methods on nanosphere integrity.
• To determine the most suitable sterilization technique for ophthalmic nanocarriers.

Main Methods:

• Formulation of poly(epsilon-caprolactone) nanospheres with Synperonic PE/F68, Synperonic PE/F127, or Cremophor RH40.
• Addition of tonicity agents, preservatives, and viscosifiers.
• Evaluation of autoclaving, gamma radiation, and sterile filtration sterilization methods.
• Analysis of physicochemical characteristics including molecular weight, particle size, and excipient stability.

Main Results:

• Autoclaving caused reactions with surfactants and tonicity agents but preserved polymer molecular weight and nanosphere diameter.
• Gamma radiation led to preservative degradation, viscosifiant depolymerization, and poly(epsilon-caprolactone) cross-linking.
• Sterile filtration was the only method that maintained the physicochemical integrity of the nanospheres.
• Sterile filtration was effective for non-viscosified vectors with small diameters.

Conclusions:

• Sterile filtration is the preferred sterilization method for poly(epsilon-caprolactone) nanospheres intended for ophthalmic use.
• Careful selection of excipients is necessary when considering autoclaving.
• Gamma radiation is unsuitable due to significant degradation of formulation components and polymer modification.