Metronidazole thermogel improves retention and decreases permeation through the skin

Abstract

Metronidazole (MTZ) is widely used as the standard antibiotic for the treatment of rosacea and, more recently, is being used off label in Brazilian hospitals for the treatment of wounds. Following oral administration, minimal amounts of active agent reaches the skin and side effects are strongly induced. Consequently, MTZ is currently being applied topically in order to improve the therapeutic efficacy with reduced side effects, with Rozex ® (RZ) (an MTZ gelled formulation) being the only marketed product. This study examined whether the use of MTZ 0.75% from thermogel formulations could improve drug retention and reduce dermal exposure compared to that by Rozex ® . Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex ® , but similar to all formulations regardless of the skin condition. On the other hand, the amount retained in the epidermis/dermis was larger for thermogel formulations; at least 4 fold that of Rozex ® , when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex ® for the topical application of MTZ with improved efficacy and reduced side effects.Uniterms: Metronidazole/evaluation. Metronidazole/drug retention. Poloxamer 407. Rosacea/treatment. Dermatopharmacokinetic.

Fast Screening Methods for the Analysis of Topical Drug Products

“…Ethanol was herein selected due to its prevalence in the literature, while the selection of propylene glycol was mainly related to the presence of this component in the qualitative formulation of some products. In fact, among the polyvalent alcohols, propylene glycol is the most frequently used co-solvent in topical products [11,38]. Nevertheless, for all drugs, ethanol demonstrated a higher solubility.…”