The Enhanced Skin Permeation of Flavonoids Via the Application of a Coamorphous in a Microemulsion Formulation

Abstract

Improving the permeability and solubility of poorly water-soluble compounds is a major difficulty in skin permeation. In this study, we investigated whether using a pharmaceutical technique such as applying coamorphous to a microemulsion enhances the skin permeation of polyphenolic compounds. The melt-quenching technique created the coamorphous system between naringenin (NRG) and hesperetin (HPT), two polyphenolic compounds with poor water solubility. By creating a supersaturated state, the aqueous solution of coamorphous NRG/HPT demonstrated improved NRG and HPT skin permeation. However, as both compounds precipitated, the supersaturation ratio decreased. In contrast to crystal compounds, incorporating coamorphous material into microemulsions enabled the preparation of microemulsions in a wider formulation range. Additionally, compared to microemulsions with crystal compounds and an aqueous suspension of coamorphous, microemulsions with coamorphous NRG/HPT increased skin permeation of both compounds by more than four times. These results suggested that interactions between NRG and HPT are maintained in the microemulsion and enhance both compounds' skin permeation. An approach for improving the skin permeation of poorly water-soluble chemicals would be to apply a coamorphous system to a microemulsion.

Keywords: Coamorphous; Hesperidin; Microemulsio; Naringenin; Skin permeability.