Different Solid Forms of Vitamin K₃ and Their Effect on the Chemical Stability

Abstract

MSB, the commercially available form of vitamin K 3 , has been widely applied in medicine, the nutrition industry, and livestock feed for decades. However, undesired degradation in an alkaline environment significantly decreases its efficacy and limits its application. Herein, polymorphism screening was performed on MSB to obtain solid forms with improved chemical stability. Two new solid forms were discovered, including form A and HB. Their crystal structures were elucidated by single crystal X-ray diffraction, and these forms were adequately characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and dynamic vapor sorption. The transformation relationships between these solid forms were fully discussed. Single-crystal-to-single-crystal transformation behavior was also detected by X-ray diffraction and hot-stage microscopy. The chemical stability in an alkaline environment of the newly discovered forms was investigated and compared with that of the marketed form. It was found that form A significantly alleviates the degradation of MSB. This gratifying chemical stability may be attributed to its compact packing pattern and the molecular conformation advantage.

Improving Stability of Vitamin B5 Through Double Salt Formation

“…For crystalline compound, the crystal packing stability of the starting material can increase the hydrolysis activation energy, and the limited mobility lower the probability of collisions between substrates and catalysts. Crystal density and packing coefficient can reflect the compactness of crystal packing and the stability of crystal, − and these related values of CP-PA, CP-IBA, and CP-HMB are listed in Table S2. Among the three double salts, CP-PA presents the highest crystal density (1.445 g/cm 3 ) and a bigger packing coefficient (71%), and CP-HMB presents the lowest crystal density (1.378 g/cm 3 ) and the smallest packing coefficient (67.8%).…”

Two anhydrous forms and one monohydrate of a cocrystal of axitinib and glutaric acid: characterization, property evaluation and phase transition study

“…1–3 Pharmaceutical cocrystals exhibit great potential in modulating the physicochemical properties, including solubility, permeability, stability, mechanical properties and so on, without compromising the chemical structures and pharmacological activity of drug substances. 4–9 Therefore, they have attracted extensive attention from both the academic and industry fields in recent years, and systematic cocrystal research has gradually become an indispensable link during the preformulation stage of drug development. 10…”

Anharmonicity and Spectra–Structure Correlations in MIR and NIR Spectra of Crystalline Menadione (Vitamin K3)

“…However, equally important are studies on the physical and chemical properties of vitamins. Different experimental methods were used to examine the correlation between the properties and the biochemical functions of vitamins, e.g., interactions of vitamins with the chemical environment and solubility in various solvents [5,6] their antioxidant potentials [7] photosensitivity and photostability [8] and the relationships between their molecular structure and chemical stability [9].…”