Solid-State Synthesis Based on Natural Leucomisine

Schrenk, a sesquiterpene γ-lactone exhibiting antioxidant, hypoglycemic, antiparasitic, and hepatoprotective activities. However, the use of leucomisine in pharmaceuticals is limited by its insufficient bioavailability associated with low aqueous solubility. Therefore, the effect of solid-state synthesis based on leucomisine using the methods of "solvent removal", "simple mixing", and "mixture heating", with disodium glycyrrhizinate as a carrier, on the aqueous solubility of leucomisine was investigated. It was established that the synthesized solid dispersions exhibit increased solubility (7-19-fold) and dissolution rate (36-100-fold) of leucomisine released from the carrier. The most pronounced stimulation of the dissolution process was observed for samples obtained using the "simple mixing" method. Based on physicochemical studies (visible-range spectrophotometry, microcrystalloscopy, investigation of optical properties of solutions, and X-Ray phase analysis), it was determined that the enhancement of solubility is attributed to the loss of crystalline state, micronization, and the solubilization process of leucomisine by the carrier, as well as to the formation of a colloidal solution of leucomisine stabilized by disodium glycyrrhizinate.