FORMULATION AND EVALUATION OF POLYMERIC MICELLES LOADED IN SITU OPHTHALMIC GEL OF CELECOXIB.

PURPOSE

Celecoxib is a promising therapeutic agent for retinal inflammatory disorders due to its anti-inflammatory, anti-VEGF, and antiproliferative activities. However, its poor aqueous solubility limits ocular bioavailability. This study aimed to develop a celecoxib-loaded polymeric micelle in situ ophthalmic gel to enhance precorneal retention and corneal permeation with prolonged ocular delivery.

METHODOLOGY

Poloxamer 188 and Poloxamer 407 were screened with different surfactants, namely Tanscutol P , Tween 80 and Span 60, either alone or in combination. Preformulation studies identified the optimum surfactant–polymer combination using the required hydrophilic–lipophilic balance (RHLB) approach. Critical micellar concentration was determined using the pyrene fluorescence probe method. Celecoxib-loaded polymeric micelles were prepared by thin-film hydration using Poloxamer 407, Span 60, and Tween 80 and evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, and in vitro drug release. The optimized formulation was selected using Pareto and desirability function analyses and incorporated into a gellan gum-based ion-activated in situ gel. The formulation was evaluated for physicochemical properties, morphology, drug release, ex vivo transcorneal permeation, histopathology, and stability.

RESULTS

At RHLB 10 (Poloxamer407: Span60: Tween 80 = 5.3:1.2:0.5 ), optimized micelles (Poloxamer407: Span60: Tween 80:Drug = 5.3:1.2:0.5:1 ) exhibited 98% ± 0.05 entrapment efficiency, 81.23 ± 0.05% drug loading, 53.3 nm particle size, low PDI, and −29.4 mV zeta potential. The in situ gel showed 99.91% ± 0.08 optical transparency and viscosities of 246 and 376 cP at room and body temperatures, respectively.Drug diffusion and permeation studies were performed using 1 mL of celecoxib in situ gel containing 0.03% w/v celecoxib. The in vitro diffusion study using a dialysis membrane demonstrated a cumulative drug diffusion of 0.065 mg/cm² at 5 h, whereas the ex vivo permeation study using goat cornea showed a cumulative drug permeation of 0.147 mg/cm² at 5 h. Histopathology indicated no significant tissue damage.

CONCLUSION

The developed formulation demonstrated stability, ocular biocompatibility, enhanced corneal permeation, and prolonged drug release, supporting its potential as a promising approach for ocular delivery of celecoxib.