Optimization and Characterization of Aqueous Micellar Formulations for Ocular Delivery of an Antifungal Drug, Posaconazole.

BACKGROUND: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic systemic side effect risk of drugs, and targeting of drugs to the site of disease. However, the optimisation of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Nanomicellar carriers have a potential to improve solubility of lipophilic drugs and, overcome ocular barriers. OBJECTIVE: In the current study, it was aimed to develop posaconazole loaded nano-micellar formulations to improve aqueous solubility of posaconazole and to characterize optimized formulations and to follow the physical stability of these formulations at room temperature (25 degrees C, 60% RH), and accelerated stability (40 degrees C, 75% RH) conditions. METHOD: Nanomicelles were prepared using thin film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Particle size, size distribution and zeta potential of the optimized nanomicellar formulations were measured by ZetaSizer Nano-ZS. Drug encapsulation efficiency of nanomicelles was quantified by HPLC. Morphology of the micelles was depicted by AFM. Stability of optimized nano-micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. RESULTS: Pre-formulation studies indicated that single D-a-tocopheryl polyethylene glycol succinate (TPGS), combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, and in a spherical shape. Additionally, the combination of TPGS and Pluronic F127 in the micelles provided a stable formulation for 90 days. CONCLUSION: The results revealed that optimized TPGS/Pluronic F127 nanomicellar formulation of posaconazole offer a potential approach for topical ocular administration.