Puerarin-Na Chelate Hydrate Simultaneously Improves Dissolution and Mechanical Behavior

Abstract

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 P2 1 , 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 b-axis. Observing along the b-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.

Structural Self-Destruction of Deep Eutectic Solvents Induced the Formation of Unusual Diamond-Shaped Crystals of Honokiol and Its Mechanistic Study

“…For tablet manufacturing in the pharmaceutical industry, powder flowability is a crucial attribute affecting many downstream processes including blending, die filling, and tableting. Numerous studies have revealed that crystal habit is one of the vital physical properties affecting powder flowability. − In this work, the flowability of hexagonal and diamond-shaped particles of HON was compared in two different ways: the angle of repose and CI . As shown in Table , the diamond-shaped crystal exhibited a smaller angle of repose than the hexagonal crystal (46.71 ± 4.73° vs 51.32 ± 2.31°), implying its better flowability. , Besides, the higher CI of hexagonal crystal (34.78 ± 4.05) indicated that it was easily cohesive, while the lower CI of diamond-shaped crystal (30.87 ± 3.82) suggested that it was free-flowing and had better flow properties. , Powder flow is sensitive to particle shape and surface texture.…”

“…Numerous studies have revealed that crystal habit is one of the vital physical properties affecting powder flowability. − In this work, the flowability of hexagonal and diamond-shaped particles of HON was compared in two different ways: the angle of repose and CI . As shown in Table , the diamond-shaped crystal exhibited a smaller angle of repose than the hexagonal crystal (46.71 ± 4.73° vs 51.32 ± 2.31°), implying its better flowability. , Besides, the higher CI of hexagonal crystal (34.78 ± 4.05) indicated that it was easily cohesive, while the lower CI of diamond-shaped crystal (30.87 ± 3.82) suggested that it was free-flowing and had better flow properties. , Powder flow is sensitive to particle shape and surface texture. Generally, more spherical particles flow better than elongated particles or particles with smoother surfaces. , As a result, the better flowability of the diamond-shaped crystal habit of HON could be attributed to its smaller aspect ratio compared to the hexagonal crystal habit, which is more elongated along the c -axis (Figure ).…”

“…75−77 In this work, the flowability of hexagonal and diamond-shaped particles of HON was compared in two different ways: the angle of repose and CI. 78 As shown in Table 3, the diamondshaped crystal exhibited a smaller angle of repose than the hexagonal crystal (46.71 ± 4.73°vs 51.32 ± 2.31°), implying its better flowability. 78,79 Besides, the higher CI of hexagonal crystal (34.78 ± 4.05) indicated that it was easily cohesive, while the lower CI of diamond-shaped crystal (30.87 ± 3.82) suggested that it was free-flowing and had better flow properties.…”

“…78,79 Besides, the higher CI of hexagonal crystal (34.78 ± 4.05) indicated that it was easily cohesive, while the lower CI of diamond-shaped crystal (30.87 ± 3.82) suggested that it was free-flowing and had better flow properties. 76,78 Powder flow is sensitive to particle shape and surface texture. Generally, more spherical particles flow better than elongated particles or particles with smoother surfaces.…”

Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin

“…This means that the formulation and preparation technology of the traditional gastric floating system theory are further innovative [ 159 ]. Additionally, hydroxypropyl-β-cyclodextrin (HP-β-CD), liposomes, solid lipid nanoparticles, novel porous silica carriers, succinylated commercial whey protein isolate (S-WPI) oral sustained release carriers, casein micelles, PEG-PE micelles, nanoliposomes, and PUE-Na chelating hydrates also greatly improve the solubility and oral bioavailability of the medicine [ 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 ].…”