Solubility Preformulation Screening of Minoxidil in Different Natural Oils Using Experimental and Computational Approaches

Lipid nanocarriers present an opportunity to improve conventional drug delivery. In addition, the concomitant use of naturally occurring products with conventional medicines is garnering traction in therapeutic and cosmetic applications. Despite these advances, the rational design of lipid nanoparticles, including lipid selection, remains a challenge. We previously validated the use of Hansen solubility parameter (HSP) predictions for selecting synthetic lipids for utilization in lipid nanocarrier manufacture. Herein, we aimed to validate the use of HSP data to predict minoxidil solubility in natural and/or essential oils with known hair growth activity. We employed a dual-tiered screening strategy that integrated HSP predictions and experimental validation. Experimentally, minoxidil showed the highest solubility in shea butter, stearic acid, and rosemary oil. Further, the latter two lipids exhibited the lowest drug-lipid solubility parameter differences (ΔδT = 6.8 and 6.1 MPa^1/2, respectively) and Relative Energy Difference values (1.28 and 1.61, respectively), aligning with the abovementioned laboratory experimental determinations. These findings provide a platform for the streamlined selection of natural oils which can enhance the solubility of minoxidil, in turn having implications for drug loading and/or encapsulation efficiency in formulation of lipidic carriers with potential synergistic hair growth potential. Moreover, this work adds to our understanding of reduced empirical excipient selection for potential decreased associated material costs during formulation development of lipid nanocarriers.