Liquid form versus Foam form of Minoxidil

Which is most effective?

Various treatment modalities for androgenetic alopecia have been developed in recent years. Currently, there are several effective medications to treat androgenetic alopecia, including minoxidil and finasteride.

Minoxidil was first used as a anti hypertensive agent for refractory hypertension. It acts selectively on potassium channels and creates a vasodilatator effect on arterioles. The mechanism of action of this drug on hair growth is still unknown. Topical minoxidil shortens the telogen phase and causes premature entry of resting hair follicles into anagen; this effect may be valid for human hair follicles. (reference: Messenger AG, Rundegren J. Minoxidil: Mechanisms of action on hair growth. Br J Dermatol. 2004; 150:186–94).

Since unexpected hair growth was noted as an adverse reaction during its oral ingestion for hypertension, meticulous efforts to obtain a local effect on scalp began in the early 1980s. Topical form of minoxidil has been used since 1984 for androgenetic alopecia. Minoxidil sulfate is metabolized by sulfotransferase present in the scalp and is the active form of minoxidil molecule. (reference: Baker CA, Uno H, Johnson GA. Minoxidil sulfation in the hair follicle. Skin Pharmacol. 1994;7:335–9).

Although the exact mechanism remains poorly understood, several theories have been proposed. The most accepted mechanism is related to the vasodilatator effect of the molecule. Increased blood flow to the scalp may stimulate hair growth. Other mechanisms are focused on hair follicle proliferation, which is boosted by minoxidil. (reference: Wester RC, Maibach HI, Guy RH, Novak E. Minoxidil stimulates cutaneous blood flow in human balding scalps: Pharmacodynamics measured by laser Doppler velocimetry and photopulse plethysmography. J Invest Dermatol. 1984;82:515–7).

In this concept, minoxidil might be thought to be similar to epidermal growth factor.(reference: Rogers NE, Avram MR. Medical treatments for male and female pattern hair loss. J Am Acad Dermatol. 2008;59:547–66. quiz 567-8).

There are two main forms of topical minoxidil molecule. One is the liquid formulation and the other is the foam formulation. Both formulations are subcategorized on the basis of their minoxidil content, such as 2% minoxidil (Minoxidil regular strength form) or 5% minoxidil (Minoxidil extra strength form). It has been proved that 2% minoxidil was less effective than 5% minoxidil in producing the desired result. (reference: Olsen EA, Dunlap FE, Funicella T, Koperski JA, Swinehart JM, Tschen EH, et al. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2002;47:377–85).

The liquid formulation contains propylene glycol, water, and alcohol. Propylene glycol is needed as a vehicle to solve minoxidil. However, most of the adverse reactions are related to hypersensitivity of propylene glycol. Itching, contact dermatitis and squamation of the scalp are attributed to propylene glycol content of topical minoxidil solution. (reference: Friedman ES, Friedman PM, Cohen DE, Washenik K. Allergic contact dermatitis to topical minoxidil solution: Etiology and treatment. J Am Acad Dermatol. 2002;46:309–12).

With these aesthetic concerns, the topical foam of minoxidil was developed, which is propylene glycol-free. In the literature, there is no comparative study between the two formulations in humans.

In an animal study, the foam formulation was found as effective as the liquid formulation.(reference: Huang T, Garceau ME, Ramstad T, Stehle RG. Rapid determination of trace amounts of minoxidil in hamster skin follicles with various formulations using narrow-bore LC/EC. J Pharm Biomed Anal. 2005;38:532–6).

It is a fact that the stratum corneum functions as a barrier for skin absorption and abraded or eczematized skin is a weak skin barrier, which leads to enhanced absorption of topical medications. In a study conducted by Wester et al., 5% topical liquid form of minoxidil was observed to cause the greatest increase in the cutaneous blood flow by using Doppler velocimetry and photopulse plethysmography comparing to 1% and 3% topical liquid form of minoxidil. This finding suggested that increasing minoxidil concentration correlates with increasing hair growth. (reference: Wester RC, Maibach HI, Guy RH, Novak E. Minoxidil stimulates cutaneous blood flow in human balding scalps: Pharmacodynamics measured by laser Doppler velocimetry and photopulse plethysmography. J Invest Dermatol. 1984;82:515–7).

In conclusion, the new alternative for topical minoxidil in the form of foam is effective from cosmetic point of view. Although contact dermatitis side effect of topical minoxidil liquid form is disturbing for many patients cosmetically, it is possible that the liquid form has a better absorption because of the epidermal disturbance due to contact dermatitis. However, this question remains unresolved until further human studies are initiated.