Cocrystallization-Mediated Property Enhancement of Hinokitiol

Hinokitiol (Hin) is a natural essential oil with broad-spectrum antimicrobial activity and low toxicity. It has been widely used in daily life, including as a food additive, an oral care ingredient, and a cosmetic component. However, its widespread use is significantly constrained by inherent limitations including photodegradation, a low melting point, and high volatility. In this study, a solvent-assisted grinding method was applied to cocrystal synthesis. Five novel solid forms of hinokitiol were successfully prepared. The melting points of the obtained cocrystals were increased by up to 40 °C compared to pure hinokitiol. In the photostability assessment, the hinokitiol-tert-butylhydroquinone (Hin-TBHQ) cocrystal exhibited exceptional stability. It remained >99% of hinokitiol content even after 30 days of continuous illumination. Furthermore, the volatilization rate of the Hin-TBHQ cocrystal was reduced by 1 order of magnitude (10-fold) compared to pure hinokitiol. Additional evaluations, including thermal stability study and long-term stability study, were also conducted. All results indicate that the Hin-TBHQ cocrystal is a promising solid form of hinokitiol, which is expected to facilitate the expansion of its application scope in various industrial scenarios.