Lipid Nanoemulgel Therapy for the Treatment of Keratoconjunctivitis Sicca: Cyclosporine Formulation Characterization and In-vitro Evaluation

Abstract

Nanoparticulate carrier systems play a significant part in enhancing ocular bioavailability. Emulgels are a potential new delivery method for the administration of lipophilic drugs like cyclosporine A (CsA). In the present research work, CsA, the immunomodulatory drug with a wide safety profile, has been formulated into nanoemulgel for treating vision-threatening ocular surface disorder viz. Keratoconjunctivitis sicca. The objective of this study was to prepare lipid-based nanoemulsion gel of CsA aiming to prolong corneal residence time and increase ocular bioavailability. Ophthalmic nanoemulgel was prepared using suitable vehicles, preservatives, hydrophilic and lipophilic emulsifiers viz croduret 40, poloxamers, spans, polyethylene glycol, polyoxyethylene 40 stearate, etc., by probe sonication method. It was evaluated for physical appearance, particle size, pH, viscosity, drug release, assay, and stability, etc. using appropriate methods. The pH and osmolarity of transparent ocular liquigel were 7.2 and 155 mOsm/L respectively. The particle size analysis and cryo scanning electron microscopic images of ocular nanoemulgel showed a monodisperse system containing a globule mean size of 190.2 ± 8.93 nm. The drug content was 99.5% w/w and the in-vitro diffusion studies showed that the medication was released for 6 hours; followed first-order kinetics with a high regression coefficient (r2) of 0.982. The lipid carrier-based topical cyclosporine ophthalmic liquigel was developed and evaluated. The in-vitro study has shown uniform, smooth-surfaced globules of size < 200 nm and prolonged drug release up to 6 hours; thus indicating increased corneal residence by nanocarrier-based gel system.