Freeze drying optimization of polymeric nanoparticles for ocular Flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability.

Freeze drying optimization of polymeric nanoparticles for ocular Flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability.

Drug Dev Ind Pharm. 2017 Jan 03;:1-36

Authors: Ramos Yacasi GR, Calpena-Campmany AC, Egea Gras MA, Espina García M, García López ML

Abstract
CONTEXT: The stabilization of flurbiprofen loaded poly-Ɛ-caprolactone nanoparticles (FB-PƐCL-NPs) for ocular delivery under accurate freeze-drying (FD) process provide the basis for a large-scale production and its commercial development.
OBJECTIVE: Optimization of the FD to improve long term stability of ocular administration's FB-PƐCL-NPs Methods: FB-PƐCL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary dying (PD) were studied and optimized through freeze-thawing test and freeze-drying microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) was used to study interactions components.
RESULTS: Optimized FB-PƐCL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted at precooling at +10°C for 1 h, freezing at -50°C for 4 h, PD at +5°C and 0.140 mbar for 24 h and a SD at 45°C during 10 h. These conditions showed 188.4±1.3 nm, 0.087±0.014, 85.5±1.4%, 0.61±0.12%, -16.4±0.1 mV and 325±7 mOsmol/Kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability > 12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after freeze-drying.
CONCLUSIONS: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the freeze-drying process.

PMID: 28044462 [PubMed - as supplied by publisher]

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