Background:
Topical therapy is preferred for the management of ocular fungal infections due to its
superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the
site of disease. However, the optimization 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. Micellar carriers have the potential to improve the solubility of lipophilic drugs
and, overcome ocular barriers.
Objective:
In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve
aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical
stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH)
conditions.
Method:
Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed
to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle
size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS.
The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was
depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution,
zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion
cells.
Results:
Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a
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, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole
from the micelles was higher than that of suspension.
Conclusion:
The results revealed that the optimized micellar formulation of posaconazole offers a potential approach
for topical ocular administration.
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