Compendium of the most significant studies with reference to properties, intake, effects.

Barbareschi M. The use of minoxidil in the treatment of male and female androgenetic alopecia: a story of more than 30 years. G Ital Dermatol Venereol. 2018 Feb;153(1):102-106. doi: 10.23736/S0392-0488.17.05781-9. 

Abstract. Even if minoxidil has been known for over 30 years as "hair growth stimulator" the precise mechanism of its action is not completely elucitated. Minoxidil shortens telogen, accelerates telogen-exogen phase and causes the premature entry of resting hair follicles into anagen phase. Moreover, minoxidil increases hair follicle size. A large part of hair treatment scientific literature confirms the efficacy of topically applied minoxidil in humans. In particular, patients treated with minoxidil showed a significant increase in "non vellus" hair count starting from baseline. Preparation of minoxidil requires molecule stability and solubility. Today are available on the market minoxidil-based formulations having low-concentration of propylene glycol to obtain preparations with a better cosmetical acceptance and dermatological safety. The body of evidences indicates that minoxidil still represent a milestone in the treatment of androgenetic alopecia and that its story is going on.

Tata S, Weiner N, Flynn G. Relative influence of ethanol and propylene glycol cosolvents on deposition of minoxidil into the skin. J Pharm Sci. 1994 Oct;83(10):1508-10. doi: 10.1002/jps.2600831026.

Abstract. Minoxidil, a potent antihypertensive, is moderately effective in the treatment of hair loss when it is applied to the scalp as a 2% solution in 60% ethanol, 20% propylene glycol and 20% water. Important questions remain concerning both the mechanism of delivery and the pathway of penetration of this drug from its ternary solvent system. Since preliminary studies in our laboratory indicated that water in the formulation influenced permeation far less than the other two solvents, we examined the relative deposition and penetration influences of binary combinations of ethanol and propylene glycol. When 50 microL/cm2 of the formulations was spread over hairless mouse skin sections mounted in Franz diffusion cells, only small amounts of minoxidil were actually recovered from the receiver compartments. Nevertheless, more minoxidil penetrated the skin as the proportion of ethanol in the mixtures was increased. To determine if these in vitro results formed a representative picture of the in vivo behaviors of these vehicles, selected deposition experiments were performed on live, anesthetized mice under experimental conditions similar to those used in the diffusion cell work. The good agreement between in vivo and in vitro studies may be a result of the relatively fast partitioning of the drug into the skin as compared to its diffusion through the skin.

Lee SW, Juhasz M, Mobasher P, Ekelem C, Mesinkovska NA. A Systematic Review of Topical Finasteride in the Treatment of Androgenetic Alopecia in Men and Women. J Drugs Dermatol. 2018 Apr 1;17(4):457-463.

Abstract. Currently, only topical minoxidil (MNX) and oral finasteride (FNS) are approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of androgenetic alopecia. Although FNS is efficacious for hair regrowth, its systemic use is associated with side effects limiting long-term utilization. Exploring topical FNS as an alternative treatment regimen may prove promising.

Suchonwanit P, Thammarucha S, Leerunyakul K. Minoxidil and its use in hair disorders: a review. Drug Des Devel Ther. 2019 Aug 9;13:2777-2786. doi: 10.2147/DDDT.S214907. 

Abstract. ...Despite its widespread application, the exact mechanism of action of minoxidil is still not fully understood. In this article, we aim to review and update current information on the pharmacology, mechanism of action, clinical efficacy, and adverse events of topical minoxidil.

Markovic M, Zur M, Garsiani S, Porat D, Cvijić S, Amidon GL, Dahan A. The Role of Paracellular Transport in the Intestinal Absorption and Biopharmaceutical Characterization of Minoxidil. Pharmaceutics. 2022 Jun 27;14(7):1360. doi: 10.3390/pharmaceutics14071360. 

Abstract. The purpose of this study was to evaluate mechanisms behind the intestinal permeability of minoxidil, with special emphasis on paracellular transport, and elucidate the suitability of minoxidil to be a reference drug for Biopharmaceutics Classification System (BCS). 

Qiu S, Fraser SP, Pires W, Djamgoz MBA. Anti-invasive effects of minoxidil on human breast cancer cells: combination with ranolazine. Clin Exp Metastasis. 2022 Aug;39(4):679-689. doi: 10.1007/s10585-022-10166-7.

Abstract. A plethora of ion channels have been shown to be involved systemically in the pathophysiology of cancer and ion channel blockers can produce anti-metastatic effects. However, although ion channels are known to frequently function in concerted action, little is known about possible combined effects of ion channel modulators on metastatic cell behaviour. Here, we investigated functional consequences of pharmacologically modulating ATP-gated potassium (KATP) channel and voltage-gated sodium channel (VGSC) activities individually and in combination....

Randolph M, Tosti A. Oral minoxidil treatment for hair loss: A review of efficacy and safety. J Am Acad Dermatol. 2021 Mar;84(3):737-746. doi: 10.1016/j.jaad.2020.06.1009. 

Abstract. Although topical minoxidil is an effective treatment option for hair loss, many patients are poorly compliant because of the necessity to apply the medication twice a day, undesirable hair texture, and scalp irritation.

Gupta AK, Foley KA. 5% Minoxidil: treatment for female pattern hair loss. Skin Therapy Lett. 2014 Nov-Dec;19(6):5-7. 

Abstract. Minoxidil is a Health Canada and US FDA-approved medication for hair loss in men and women. While 5% minoxidil foam has been approved for men since 2006, Health Canada and the FDA only approved 5% minoxidil foam for female pattern hair loss (FPHL) in 2014. Recent Phase III clinical trials demonstrated the efficacy of once daily 5% minoxidil foam for treatment of FPHL, where a significant change from baseline in the target area hair count was observed compared to placebo. Similar changes in hair count for 5% foam and twice daily 2% minoxidil solution established noninferiority of the 5% foam formulation. Five percent minoxidil foam provides an additional option for women with FPHL and will soon be available in Canada.

Sanabria BD, Palmegiani E, Seron AF, Perdomo YC, Miot HA, Müller Ramos P. Prospective cardiovascular evaluation with 24-hour Holter and 24-hour ambulatory blood pressure monitoring in men using 5-mg oral minoxidil for androgenetic alopecia. J Am Acad Dermatol. 2022 May 18:S0190-9622(22)00821-0. doi: 10.1016/j.jaad.2022.05.026.

Abstract. Low-dose oral minoxidil (LDOM; 0.25-5 mg/d) is an effective treatment for androgenetic alopecia. However, even at low doses, minoxidil has been associated with electrocardiogram alterations (premature ventricular contractions and T-wave inversion) and palpitations. 

Torrado-Salmeron C, Laguna A, Guillén A, Saro MG, Matji A, Torrado JJ, Serrano DR. Tailoring Rational Manufacturing of Extemporaneous Compounding Oral Dosage Formulations with a Low Dose of Minoxidil. Pharmaceutics. 2022 Mar 17;14(3):658. doi: 10.3390/pharmaceutics14030658. 

Abstract. Low amounts of minoxidil in oral dosage forms are commonly prescribed as anti-alopecic pharmacological treatments. Side effects are usually related to individual susceptibility. However, poor drug content and mass uniformity can lead to a potential risk of overdosing, and higher chances to experience side effects. The impacts of four formulation variables on drug content and mass pharmaceutical quality attributes were studied with an experimental design at two levels. The first variable (A) was the particle size of the direct compression microcrystalline cellulose (MCC) used as a diluent (Avicel® PH 101 vs. LP 200). The second variable (B) was the type of production process (direct filling vs. wet granulation). The third variable (C) was the particle size of riboflavin added as a color mixture indicator agent (granular vs. milled). The fourth variable (D) was the type of oral solid dosage form (capsule vs. tablet). In half of the formulations, the mean minoxidil content and minoxidil uniformity were out of the specification limits of the Pharmacopoeia, demonstrating the importance of carefully selecting the excipients as well as the utilized process when manufacturing low oral dosage minoxidil formulations. The best minoxidil content uniformity was achieved when using MCC LP 200, wet granulation, granular riboflavin, and capsules. However, tablets are the recommended dosage form when utilizing Avicel® PH 101 or direct filling. Meeting these criteria, the content and mass uniformity are more likely to meet the specification limits of the Pharmacopeia. Techniques such as NIR spectroscopy should be implemented to control the quality of extemporaneous compounding formulations with a low dose of active ingredient.