Minoxidil as a Prodrug: Review of Chemical, Pharmacological, and Technological Aspects in Alopecia Therapeutics.

Alopecia is a prevalent condition that affects both sexes, characterised by miniaturisation of hair follicles and changes in the dynamics of the hair cycle, such as androgenetic alopecia associated with various systemic factors, including the COVID-19 pandemic. Minoxidil (base), initially developed as an oral antihypertensive, is currently used in the treatment of alopecia, acting as a prodrug that requires hepatic sulphation to generate its active metabolite, minoxidil sulphate. Topical formulations use minoxidil sulphate, the active pharmaceutical ingredient, directly on the hair follicles. Pharmacogenomic studies highlight the critical role of SULT1A1 enzyme variability in modulating treatment response, supporting personalised therapeutic strategies. Despite challenges related to low water solubility, high permeability, and narrow therapeutic index, emerging pharmaceutical technologies, including minitablets, orodispersible forms, sublingual preparations, and modified release systems, offer the potential to optimise absorption, increase dosing accuracy, and reduce adverse effects. This review consolidates current knowledge on the chemistry, pharmacology, pharmacogenomics, and technological aspects of minoxidil (base) for systemic use, emphasising translational developments that may redefine its clinical applications and contribute to safer and more standardised therapies. The integration of medicinal chemistry, pharmaceutical technology, clinical pharmacology, and regulatory guidance is expected to promote oral minoxidil as a reliable, effective, and patient-centred therapeutic option for alopecia.