Drug-Bridge-Drug Ternary Cocrystallization Strategy for Antituberculosis Drugs Combination

Abstract

Realizing combination drugs at a molecular level via drug–drug cocrystallization opens a new pathway for effective therapeutic hybrids. A “drug-bridge-drug” strategy is developed to cocrystallize two first-line antitubercular drugs isoniazid and pyrazinamide using fumaric acid as the bridge, overcoming the issue of hardly cocrystallizing two different drugs. The first example of ternary cocrystal with combination drugs exhibits optimized formulation capacity and in vitro/vivo synergistic effects, which provides a new insight into antituberculosis combination drugs.