Mechanosynthesis of magnolol multicomponent crystalline solids for improved natural antibiotics and customizable release profiles.

[Display omitted] • Mechanochemical synthesis of multi-component crystals of the natural antibiotic magnolol. • Enhanced dissolution properties lead to increased antibacterial activity. • Construct of structure–activity relationship and managing of multi-component crystal on physicochemical properties. • Design of isostructural cocrystal and evaluation of pharmaceutical properties. Antibiotic is one of the most important discoveries in human and animal medicine. However, the inefficient use of antibiotics has caused widespread and persistent contamination of ecosystems, setting off microbial resistance storms. Magnolol is a botanical antibiotic, but poor physicochemical properties result in low bioavailability. Increasing solubility of magnolol can help to reduce the doses of medications to patients, minimize bothersome side effects. In this work, three novel multicomponent crystalline solids were synthesized from magnolol and isomeric coformers by mechanochemistry. It was found that the multicomponent crystalline solids achieved the customizable release profile of magnolol by manipulating the substituent positions of the isomers and complexation. Antibacterial activity test showed that bioactivity on two bacteria was considerably improved by designed MGN multicomponent crystals. In addition, the coformers controlled the dissolution behavior and further stabilized the improvement according to the variable statistical analysis. In conclusion, the properties of antibiotic multicomponent solids can be manipulated through the coformers. This provides an effective strategy for managing the release of drugs to meet individual biological differences and diverse therapeutic needs. [ABSTRACT FROM AUTHOR]