Effects of Solvents on Spherical Crystals of Minoxidil

Minoxidil, a topical vasodilator primarily used to treat androgenetic alopecia, has a huge market but remains underexplored in the control of its spherical crystals. Spherical crystal structure is a vital morphology due to its superior powder characteristics in pharmaceutical manufacturing. Even though solvent-induced single crystals have been well studied, there have been few studies on the solvent-mediated morphology of spherical aggregates. In this paper, several kinds of spherical crystals, such as plate crystal aggregates, nanocrystal aggregates, and core–shell aggregates, are prepared in alcoholic solvents with different carbon chain lengths. Particularly, spherulite aggregates (SLA), which are observed for the first time, are produced in a n-butanol–ethyl acetate mixture. Also, the growth mechanism of SLA is analyzed in detail, and it is found that the addition of ethyl acetate could change the morphology of spherulites and promote agglomeration between them compared to pure solvent systems without ethyl acetate. In addition, the method of generating supersaturation is significant by specifying the morphology of the spherulite. The flowability and other powder properties of SLA are also investigated, with a 15.8% reduction in the repose angle and 24.7% of the Hausner ratio. Furthermore, this paper reports a unique butterfly-shaped crystal of minoxidil, which undergoes a spontaneous growth in a homogeneous solution, not from agglomeration.