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Published on: April 6, 2016
Microfluidic ocular formulation of voriconazole designed for hospital production
Louise Stinat1,2, Marie Bonnin1,3, Jean-Christophe Gimel1,3
1Université d'Angers, CHU Angers, INSERM, CNRS, MINT, SFR, ICAT, F-49000, Angers, France.
Abstract:
Fungal keratitis is a serious corneal infection with a limited therapeutic panel. Voriconazole, an azole antifungal, has been shown to be effective against many of the fungal strains involved in this type of infection. The absence of an ocular dedicated formulation on the market has led to the use of the sterile commercial cyclodextrin based formulation as a hospital preparation with some drawbacks. The aim of this study was to design a dedicated formulation for ocular delivery using oil-in-water nanoemulsion. A 0.4% voriconazole nanoemulsion was formulated with an oil and two surfactants, complying with the standards set by the authorities and literature. The nanoemulsion was produced using the phase inversion composition method. It was also formulated using microfluidic technology, suitable for hospital transposition. The mean droplets size was around 100 nm and zeta potential was negative. The pH and osmolality have been adjusted without destabilizing the nanoemulsion. Additionally, it was demonstrated that the formulation consists of two compartments: oil nanodroplets and residual micelles. Voriconazole was preferentially found in the micellar compartment. Finally, in vitro determination of minimal-inhibition-concentration tests were carried out on Aspergillus and Fusarium fungal species and compared to the 1% current hospital preparation. These tests showed that our formulation was no less effective than the hospital preparation.
Insights
A new oil-in-water nanoemulsion formulation for voriconazole offers an effective alternative for fungal keratitis treatment. This ocular delivery system demonstrates comparable efficacy to existing hospital preparations.
Area of Science:
- Ophthalmology
- Pharmaceutics
- Mycology
Background:
- Fungal keratitis is a severe corneal infection with limited treatment options.
- Current voriconazole formulations for ocular use are hospital preparations with drawbacks.
- There is a need for a dedicated, effective ocular formulation for voriconazole.
Purpose of the Study:
- To design and characterize a novel oil-in-water nanoemulsion for ocular delivery of voriconazole.
- To evaluate the efficacy of the developed nanoemulsion against key fungal species causing keratitis.
Main Methods:
- Formulation of a 0.4% voriconazole nanoemulsion using the phase inversion composition method and microfluidic technology.
- Characterization of nanoemulsion properties including droplet size, zeta potential, pH, and osmolality.
- In vitro minimal inhibitory concentration (MIC) testing against Aspergillus and Fusarium species.
Main Results:
- A stable voriconazole nanoemulsion with a mean droplet size of approximately 100 nm and negative zeta potential was successfully prepared.
- The formulation demonstrated stability after pH and osmolality adjustments.
- Voriconazole was found to preferentially partition into the micellar compartment of the nanoemulsion.
- In vitro MIC tests showed the nanoemulsion was as effective as the current 1% hospital preparation against tested fungal strains.
Conclusions:
- A novel voriconazole oil-in-water nanoemulsion is a viable and effective formulation for ocular delivery.
- This formulation addresses the limitations of current hospital preparations for fungal keratitis.
- The microfluidic preparation method is suitable for hospital transposition, offering a promising therapeutic option.
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