Development and characterization of Novel topical oil/PEG creams of voriconazole for the treatment of fungal infections

Voriconazole (VRC), a second generation triazole derivative emerged as a promising candidate for the treatment of fungal infections. Voriconazole is commercially available as oral and intravenous formulations, however administration through these routes is associated with several side effects like hepatotoxicity, photopsia and abdominal pain. Hence, percutaneous delivery of voriconazole through creams or hydrogels would be beneficial for preventing side effects due to other routes of administration.

Highlights

Oil/PEG cream was prepared to prevent hydrolytic degradation of voriconazole.

Oil/PEG vorcionazole cream composition was optimized to prepare a stable cream.

Melt extrusion process was used as a continuous manufacturing technique.

Transcutol® P increased the permeation of voriconazole across human cadaver skin.

Oil/PEG cream can be used to incorporate moisture sensitive drugs.

Voriconazole may potentially undergo degradation in formulations containing water. The objective of the study was to prepare a stable biphasic semisolid formulation using oil and PEG. The melt extrusion process was used as a continuous manufacturing technique for preparation of oil/PEG cream. Formulation composition and processing conditions were optimized based on the compatibility and pre-formulation studies. The developed creams were characterized for content uniformity, viscosity and in vitro drug release. The effect of Transcutol® P and camphor: menthol (1:1) on the permeation of voriconazole was evaluated by ex vivo permeation studies.

The voriconazole in oil/PEG formulation (93.44 ± 1.59%) were stable for 3 months compared to control voriconazole hydrogel formulation (10.67 ± 0.03%) at 25 °C (60% RH). The formulation with Transcutol® P used as a permeation enhancer increased voriconazole permeation 9 folds compared to formulation without permeation enhancer. In conclusion, a stable oil/PEG voriconazole cream was successfully developed using continuous manufacturing process and can be used as alternate for intravenous/oral voriconazole for treatment of fungal skin infections.

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Article information: Abhishek Shettar, Vijay Kumar Shankar, Srinivas Ajjarapu, Vijay I. Kulkarni, Micheal A. Repka, S. Narasimha Murthy, Development and characterization of Novel topical oil/PEG creams of voriconazole for the treatment of fungal infections, Journal of Drug Delivery Science and Technology, 2021. https://doi.org/10.1016/j.jddst.2021.102928.