Is alcohol-free minoxidil effective?

Alcoholic formulations in the form of 2% and 5% solution and 5% foam were approved by the FDA in 1988, 1991, and 2016 respectively for the management of male pattern baldness. These older formulations rely heavily on alcohol and propylene glycol to bring complete dissolution and prevent crystallisation of Minoxidil. In addition, they also help with the penetration of Minoxidil through the stratum corneum.

This article will focus on:

What is the role of alcohol in these formulations?
Is there scientific evidence for alcohol-free minoxidil?
What are the benefits of alcohol-free minoxidil?
Are all alcohol-free formulations the same?

Rogain, Regain, HairAgain and friends ...

Regain is a popular minoxidil product sold in Australian pharmacies. It is known by the name Rogain in the United States and other parts of the world. Since the patent for Rogain expired, other brands have marketed their own version, all with the same formulation. Why the same formulation? What role does alcohol and propylene glycol have?

Minoxidil is not soluble in water and requires the addition of propylene glycol and alcohol to bring about complete dissolution. Studies show Minoxidil is highly soluble in propylene glycol, followed by ethanol.

The maximum concentration Minoxidil can be dissolved using Propylene Glycol was found to be 7.5%, after which it becomes unstable and will crystalise. In 2024, Médicii Laboratories was been able to demonstrate that Minoxidil can be dissolved without propylene glycol and alcohol at concentrations exceeding 7.5% using Olevit™, a proprietary fatty acid distilled in glycerine.

Studies comparing different delivery solvents found that ethanol and propylene glycol also had the highest rate of drug penetration through the stratum corneum (aka top layer of the skin). Does greater penetration equal better results?

Not necessarily. Think of penetration as entering a room. Once you enter the front door, you want to be able to walk to the other side of the room freely. In science, this is described as the drug's diffusion co-efficient or diffusivity. Therefore, Minoxidil's activity also depend on its ability to leave stratum corneum.

Are alcohol-free minoxidil formulations effective?

Emerging studies show non-alcoholic Minoxidil formulations produce similar benefits compared with alcoholic formulations and with significantly less adverse effects.

A 2023 study published in the International Journal of Trichology showed that patients had improved skin hydration, reduced scalp inflammation and reduced scalp itching when they used alcohol-free Minoxidil.

In contrast, alcohol-based formulations showed an increase in scalp redness and dryness after day 15 and day 30 respectively.

Cetosomal Minoxidil have also been tested against alcoholic Minoxidil. Sattur (2023) demonstrated that 5% cetosomal minoxidil showed improved patient safety with similar efficacy when administered twice daily.

Are all alcohol-free formulations the same?

Not all alcohol-free formulations are the same.

Some bulk ingredients contain a small amount of alcohol. These formulations are formerly known as hydro-alcoholic formulations. Whilst a small amount of alcohol is not enough to provoke sensitive skin, they are not truly alcohol-free.

The ability for Minoxidil to leave the stratum corneum (diffusivity).

Other skin conditioning benefits.

Author: Daniel Atkinson (B Pharm)

References:

Udare, S et al (2023). "Low-Alcohol or Alcohol-Free Minoxidil Formulation for the Management of Androgenic Alopecia: an Indian Perspective." International Journal of Trichology. 15(1): p13-17, Jan-Feb 2023.
Yan, H et al (2011). "Solubility of Minoxidil in Methanol, Ethanol, 1-Propanol, 2-Propanol, 1-Butanol, and Water from (278.15 to 333.15) K ." J. Chem. Eng. Data 2011, 56, 5, 2720–2722
Tata, S et al (1995). Penetration of Minoxidil from Ethanol/PG: Effect of application volume and occlusion. J Pharm. Sciences. v84(6). June 1995, Pages 688-691.
Sattur, S (2023). "Comparative clinical study evaluating the efficacy and safety of topical 5% Cetosomal Minoxidil and 5% Alcohol-Based Minoxidil Solutions for the treatment of androgenic alopecia in Indian Men."Cureus 15(10): e46568. doi:10.7759/cureus.46568
American Chemical Society
Sarkar, R et al (2020). "Topical 5% Minoxidil Novel Formulation and Alcohol-based conventional solutions in treatment of androgenic alopecia in Indian men: A randomised double-blind study." J Dermatology and Therapy. v10, p469-479