Design, Preparation, and Ex Vivo Skin Permeation of Doxepin Microemulsion System for Topical Delivery.

BACKGROUND

Doxepin (DX) is used orally to relieve itching but can cause side effects like blurred vision, dry mouth, and drowsiness due to its antimuscarinic effect. To reduce these adverse effects and improve skin permeation, DX is being developed in topical formulations. This study aims to improve DX skin absorption by developing a microemulsion (ME) formulation (ME-DX).

METHOD AND MATERIALS: ME formulations containing 5% DX were prepared using the phase diagram method with a mixture of essential oil (oleic acid), surfactant (Tween 80 and Labrazol), and cosurfactant (propylene glycol or PG). The physicochemical properties of these formulations were assessed to improve the topical application of DX.

RESULTS

ME droplet sizes ranged from 9.8 to 61.6 nm, with viscosities between 114 and 239 cps. Studies showed a significant correlation between DX release percentages and viscosity. ME-DX-2 released 46.51% of the drug after 24 h. Selected ME-DX formulations demonstrated Weibull, Log Wagner, and zero-order release kinetics, and improved skin permeability. ME-DX-8 exhibited an eightfold increase in Jss and P parameters compared to the control group. MEs maintained 99.9% of DX after 6 months without color changes or phase separation, indicating long-term stability.

CONCLUSION

This research demonstrates that altering the content and composition of MEs can change the physicochemical properties and permeability characteristics of DX when introduced into rats. Additionally, ME formulation shows promise as an effective vehicle for topical DX delivery in atopic dermatitis treatment.