Novel stable micellar formulation for ocular delivery of nepafenac: optimization, characterization and in-vitro evaluation.

OBJECTIVE

The objective of this study was to develop a stable clear ophthalmic nano-micellar formulation of Nepafenac.

SIGNIFICANCE: The current marketed suspension formulation of nepafenac indicated for post-surgical uveitis is associated with higher manufacturing complexity and cost due to the need for sterile drug substance and specialized aseptic processing inherent to suspension-based ophthalmic products. It also exhibits limitations in patient compliance due to relatively high viscosity, lacrimation, and foreign body sensation following instillation.

METHODS

Pre-formulation study was done to identify the excipients required. Systematic changes in the concentration of surfactant and crystal inhibitor along with other excipients led to the development of stable nano-micellar formulation. Box-behnken method was used for the optimization. The optimized micellar composition was evaluated for physicochemical tests particle size, zeta potential, cloud point, osmolality pH, assay of drug, entrapment efficiency and dynamic viscosity. Further in-vitro cell viability, in-vitro release, ocular tolerance test and stability evaluation were also performed.

RESULTS

Average particle size of the micelle ranged from 10 to 20 nm, 43.5 mPas dynamic viscosity, osmolality of 319 mOsm/Kg, pH 7.4 and cloud point of 59.7 °C. The optimized formulation demonstrated in-vitro safety as confirmed by MTT cell viability and HET-CAM ocular irritation assays, and exhibited physicochemical stability for up to 6 months under real-time storage conditions.

CONCLUSION

The optimized micelle formulation can serve as a better alternative for ophthalmic delivery of nepafenac.