Four Novel Pharmaceutical Cocrystals of Oxyresveratrol, Including a 2 : 3 Cocrystal with Betaine

Abstract

Cocrystal engineering can alter the physicochemical properties of a drug and generate a superior drug candidate for formulation design. Oxyresveratrol (ORV) exhibits a poor solubility in aqueous environments, thereby resulting in a poor bioavailability. Extensive cocrystal screening of ORV with 67 cocrystal formers (coformers) bearing various functional groups was therefore conducted using grinding, liquid-assisted grinding, solvent evaporation, and slurry methods. Six cocrystals (ORV with betaine (BTN), L-proline (PRL), isonicotinamide, nicotinamide, urea, and ethyl maltol) were found, including four novel cocrystals. Powder X-ray diffraction, low frequency Raman spectroscopy, and thermal analysis revealed unique crystal forms in all obtained samples. Conventional Raman and infrared data differentiated the cocrystals by the presence or absence of a hydrogen bond interacting with the aromatic ring of ORV. The crystal structures were then elucidated by single-crystal X-ray diffraction. Two new cocrystals consisting of ORV : BTN (2 : 3) and ORV : PRL : H 2 O (1 : 2 : 1) were identified, and their crystal structures were solved. We report novel cocrystalline solids of ORV with improved aqueous solubilities and the unique cage-like crystal structures.

Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying

“…The use of an amorphous form, changing the active pharmaceutical ingredient (API) to a salt, or inducing co-crystallization, are all useful approaches to improve drug solubility. 1,[12][13][14][15][16] Amorphous forms of drugs have high potential energy, which indicates high solubility. However, amorphous forms crystallize easily due to their instability, and the solubility decreases with crystallization.…”

Characterization of Ambroxol and Its Hydrochloride Salt Crystals by Bromine K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy and X-Ray Crystal Structure Analysis

“…[1][2][3] Therefore, investigating API crystal polymorphism is an essential aspect of pre-formulation and manufacturing quality control. Various analytical methods have been used to characterize API crystal polymorphs, including powder X-ray diffraction (PXRD), 4) thermal analysis, single-crystal X-ray diffraction (SCXRD), 5) Raman spectroscopy, 6) and solid-state NMR. 7) We have characterized API crystal forms by X-ray absorption fine structure (XAFS) spectroscopy, where electrons are excited when the X-ray energy exceeds the orbital energy and a sharp rise in the absorbance spectrum is observed at that energy.…”

Novel Pharmaceutical Cocrystals and Solvate Crystals of Nobiletin, a Citrus Flavonoid with Potent Pharmacological Activity

“…The cocrystal is formed via noncovalent interactions such as hydrogen bonding or hydrophobic stacking interactions. [15][16][17][18][19][20][21] Consequently, cocrystallization has been extensively studied in recent years as a method to improve physical properties without salt formation because the dissociating groups of drugs are unnecessary. 22) Moreover, there have been reports on improvements in the solubility, hygroscopicity and physical stability of the compounds.…”