Emulgel Containing Metronidazole and Clindamycin for the Treatment of Rosacea

Rosacea is a common skin condition with quite a relevance. It currently affects at least 10% of the European population at some point after the age of 30. It is a chronic disorder that mainly affects the skin on the face and is characterized by outbreaks and remissions. Under normal circumstances, the skin face presents a wide range of commensal organisms, such as Staphylococcus epidermidis or Demodex folliculorum, but dysbiosis of the skin flora plays a relevant role in inflammatory processes and the development of the disease. Metronidazole (MD) is one of the main treatments indicated to reduce redness on the cheeks, nose, chin, or forehead and also to treat flushing, erythema, pimples, and other symptoms due in part to its anti-inflammatory action. On the other hand, clindamycin (CM) is another antibiotic used for rosacea, especially for its action against anaerobic and Gram-positive bacteria. Background/Objectives: This study aimed to develop an emulgel formulation that includes MD and CM, using excipients with non-comedogenic and non-irritating properties. Methods: The formulation was characterised physiochemically, rheological measurements were made, and short-term stability studies were carried out. In vitro release, permeation studies, toxicity an in vitro inflammation model were evaluated in a HaCaT cell model. To determine the interaction between the antibiotics, the minimum inhibitory concentration was determined separately and together using the broth microdilution method. To determine the formulation's antimicrobial activity, an agar diffusion method was used. Results: The MD-CM-gel droplet size was measured by laser diffraction and the diameter obtained was less than 2.68 ± 0.18 µm in 50% of the particles. Suitable results was observed for the short-term stability. Release and permeation data revealed sustained drug release and adequate permeation through human skin. Non-toxicity was detected and the MD showed an anti-inflammatory effect with non-interference of CM. Also, there is no antagonism between the two antibiotics and the MD-CM-gel shows better results when compared to the formulations with the antibiotics separately and to commercial formulations. Conclusions: It is suggested that, following detailed preclinical and clinical studies, MD-CM-gel could be considered as an alternative for treating rosacea.