Preparation and evaluation of a multimodal minoxidil microemulsion versus minoxidil alone in the treatment of androgenic alopecia of mixed etiology: a pilot study.

BACKGROUND: The variable success of topical minoxidil in the treatment of androgenic alopecia has led to the hypothesis that other pathways could mediate this form of hair loss, including infection and/or microinflammation of the hair follicles. In this study, we prepared a multimodal microemulsion comprising minoxidil (a dihydrotestosterone antagonist), diclofenac (a nonsteroidal anti-inflammatory agent), and tea tree oil (an anti-infective agent). We investigated the stability and physicochemical properties of this formulation, and its therapeutic efficacy compared with a formulation containing minoxidil alone in the treatment of androgenic alopecia. METHODS: We developed a multimodal oil/water (o/w) microemulsion, a formulation containing minoxidil alone, and another containing vehicle. A three-phase diagram was constructed to obtain the optimal concentrations of the selected oil, surfactant, and cosurfactant. Thirty-two men aged 18-30 years were randomized to apply 1 mL of microemulsion containing the multimodal formulation (formulation A, n = 11), minoxidil alone (formulation B, n = 11) or placebo (formulation C, n = 10) twice daily to the affected area for 32 weeks. Efficacy was evaluated by mean hair count, thickness, and weight on the targeted area of the scalp. Global photographs were taken, changes in the area of scalp coverage were assessed by patients and external investigators, and the benefits and safety of the study medications were evaluated. The physical stability of formula A was examined after a shelf storage period of 24 months. RESULTS: Formulation A achieved a significantly superior response than formulations B and C in terms of mean hair count (P < 0.001), mean hair weight (P < 0.001), and mean hair thickness (P < 0.05). A patient self-assessment questionnaire demonstrated that the multimodal minoxidil formulation significantly (P < 0.001) slowed hair loss, increased hair growth, and improved appearance, and showed no appreciable side effects, such as itching and/or inflammation of the scalp compared with the minoxidil alone and placebo formulations. These improvements were in agreement with the photographic assessments made by the investigators. Formula A was shown to be an o/w formulation with consistent pH, viscosity, specific gravity, and homogeneity, and was physically stable after 24 months of normal storage. CONCLUSION: A multimodal microemulsion comprising minoxidil, diclofenac, and tea tree oil was significantly superior to minoxidil alone and placebo in terms of stability, safety, and efficacy, and achieved an earlier response in the treatment of androgenic alopecia compared with minoxidil alone in this 32-week pilot study.