Puerarin-Na Chelate Hydrate Simultaneously Improves Dissolution and Mechanical Behavior

Puerarin monohydrate (PUEM), as the commercial solid form of the natural anti-hypertension drug puerarin (PUE), has low solubility, poor flowability, and mechanical properties. In this study, a novel solid form as PUE-Na chelate hydrate was prepared by a reactive crystallization method. Crystal structure analysis demonstrated that PUE-Na contains PUE, Na, and water in a molar ratio of 1:1:7. It crystallizes in the monoclinic space group 2, and Na is linked with PUE and four water molecules through Na ← O coordination bonds. Another three crystal water molecules occupy channels along the crystallographic -axis. Observing along the -axis, the crystal structure features a distinct tubular helix and a DNA-like twisted helix. The complexation between Na and PUE in aqueous solution was confirmed by the Na selective electrode, indicating that PUE-Na chelate hydrate belongs to a type of chelate rather than organic metal salt. Compared with PUEM, PUE-Na exhibited a superior dissolution rate (i.e., ∼38-fold increase in water) owing to its lower solvation free energy and clear-enriched exposed polar groups. Moreover, PUE-Na enhanced the tabletability and flowability of PUEM, attributing to its better elastoplastic deformation and lower-friction crystal habit. The unique PUE-Na chelate hydrate with significantly enhanced pharmaceutical properties is a very promising candidate for future product development of PUE.