A Facile Strategy to Generate High Drug Payload Celecoxib Micelles for Enhanced Corneal Permeability.

Abstract

Topical ocular drug administration aimed at providing a high drug concentration at the precorneal site accompanied with enhanced corneal permeability to avoid systemic side effects is a very important therapeutic goal in ocular disorder therapy. In the present study, the solubility of the poorly soluble drug celecoxib (CXB) was significantly improved using a facile strategy to generate a high drug payload micellar formulation. By varying the drug/polymer feed ratios, the mean diameter of the formed CXB micelles ranged from 21.34 ± 0.23 to 28.53 ± 0.11 nm, and the drug loading capacity ranged from 4.31 to 15.87%. Transmission electron microscopy (TEM) showed that the formed CXB micelles had a uniform spherical morphology. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the physicochemical properties of lyophilized CXB micelles. The obtained CXB micelles retained their properties through freeze-drying and rehydration, thereby providing long-term physicochemical stability over 3 months of storage at -20 °C. An in vitro release study showed that the CXB micelles released CXB in a sustained release manner without any apparent burst release over 72 h by the Higuchi non-Fickian diffusion mechanism. Notably, using corneas excised from rabbits, the in vitro corneal permeability of CXB from the micellar formulation was observed to be significantly greater than that of the microparticle formulation. Overall, the proposed micelles might be a promising vehicle for ophthalmic delivery of CXB with the significant enhancement of water solubility and corneal permeability.