Doxycycline monohydrate and azelaic acid Co-loaded nanoemulgel for the treatment of facial rosacea: In vitro and In vivo evaluation

Nanoemulgel have gained importance as topical delivery systems because of their potential to incorporate hydrophilic and lipophilic drugs simultaneously like emulsions and improved stability and spreadability like gels. Therefore, the current research was aimed to prepare, optimize, and evaluate the combined therapeutic efficacy of doxycycline monohydrate (DOX.H2O) and azelaic acid (AZL) loaded into a nanoemulgel (NE) against facial rosacea. The nanoemulsion was prepared via phase inversion low energy emulsification method by solubilizing DOX.H2O in peppermint oil and AZL in deionized water. The formulation was optimized using Design Expert 13. The optimized nanoemulsion has a particle size of 210.6 nm, a PDI of 0.234 and a zeta potential of −15.1 mV. SEM observations revealed the spherical morphology of oil globules, whereas FTIR results confirmed that no chemical interaction among the ingredients took place. The in vitro release study showed the burst release of 82.1 % AZL and 48.1 % release of DOX.H2O from the optimized DOX-AZL co-loaded NE in 6 h. The ex vivo permeation profile showed a minimum permeation of DOX.H2O and AZL across rat skin. Croton oil induced inflammation in mice ear confirmed the therapeutic efficacy of the prepared NE against facial rosacea. Considering the results obtained herein, the developed NE could enhance the safety and efficacy of the combination therapy against facial rosacea.