Olive Oil-Based Reverse Microemulsion for Stability and Topical Delivery of Methotrexate: In Vitro.

Hydrolysis of pharmaceutically active molecules can be in control under a confined environment of water-in-oil microemulsion. Stability of model drug methotrexate (MTX) in a sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and olive oil microemulsion system has been evaluated. The physicochemical properties of AOT-MTX-water-olive oil reverse microemulsion (MTX-RM) were examined by UV-vis, Fourier transform infrared, and X-ray diffraction techniques, and the hydrodynamic size was determined by dynamic light scattering techniques and morphologies were characterized by a transmission electron microscope and atomic force microscope. In vitro permeation of MTX-RM through treated skin and its mechanism are evaluated by a UV-visible spectrophotometer, confocal laser scanning microscope, differential scanning calorimeter, and attenuated total reflecting infrared spectroscopy (ATR). The interaction of MTX with the AOT headgroup in confined environment RM enhanced the stability of MTX without affecting the molecular integrity at room temperature. Chemical stability of MTX in MTX-RM ( W 0 = 5) is significantly higher (∼97%) at room temperature for the study period of 1 year than in MTX-RM ( W 0 = 15) (∼72%). Interaction of MTX with the AOT headgroup is also visualized by a high-resolution transmission electron microscope and is in correlation with FT-IR data of MTX-RM. The skin fluxes of MTX are 15.1, 19.75, and 22.75 times higher at water content ( W 0 ) of 5, 10, and 15, respectively, in MTX-RM in comparison to aqueous solution of MTX. The enhanced amounts of the MTX were detected using CLSM in hair follicles, sweat glands, and epidermis layer of the skin. Merging of T 2 , T 3 , and T 4 thermal peaks in one broad peak in treated skin endothermograph shows that carrier MTX-RM affects the lipid as well protein structure of the treated skin. ATR data of treated skin showed an increase in the intensity of the carbonyl peak at 1750 cm -1 (lipid), shifting of the amide II peaks, and separation of peaks in the range of 1060 to 1000 cm -1 (vibration mode of -CH 2 OH, C-O stretching, and C-OH bending peak of the carbohydrate) in comparison to control skin, which indicates that MTX-RM interacts with glycolipid and glycoprotein through carbohydrate hydroxy groups.