Co-crystallization of quercetin and isonicotinamide using solvent evaporation method

Budipratiwi Wisudyaningsih,Siswandono Siswandono,Dwi Setyawan

doi:10.4314/tjpr.v18i4.3

Budipratiwi Wisudyaningsih, Siswandono Siswandono + Show 1 more

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https://doi.org/10.4314/tjpr.v18i4.3

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Abstract

Purpose: To obtain quercetin-isonicotinamide co-crystal (CQINA) with improved physicochemical and in-vitro dissolution characteristics. Methods: Co-crystallization of quercetin (Q) and isonicotinamide (INA) in molar ratio of 1:1 was performed using solvent evaporation method with the addition of 50 mL of ethanol (99.9%, v/v). The resultant solution was thoroughly mixed and stirred at room temperature for 48 h to slowly evaporate the solvent until CQINA was obtained. The co-crystal phase was characterized using differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), scanning electron microscopy (SEM), and fourier transform infrared (FTIR) spectroscopy. In-vitro dissolution was performed by USP method II in 900 mL citrate buffer (pH 5.0 ± 0.05), with stirring at 100 rpm and at 37 ± 0.5 °C. Results: Computational approach predicted the formation of hydrogen bonds between Q and coformers used, and the interaction involved minimum energy. In CQINA thermogram, a new endothermic peak was formed with a melting point of 255.26 °C, while Q (314.85 °C) and INA (156.62 °C). Images from DSC, PXRD, SEM and FTIR showed that the crystal habits and morphologies of the CQINA differed from those of the original components. There was an improvement in the dissolution profile of CQINA, when compared with those of the original components. Conclusion: Q and INA subjected to solvent evaporation result in the formation of a CQINA with different crystal habit, which possess physicochemical characteristics different from those of its constituents. Modification of Q crystals in CQINA increases its in vitro dissolution, making it a potential pharmaceutical agent.

Highlights

Quercetin is a flavonoid possesses antioxidant, anti-cancer, anti-viral, anti-obesity, anti-bacterial and anti-inflammatory properties [1,2,3,4,5]
Binary phase diagram was drawn to confirm the existence of physical interactions between quercetin and INA, forming co-crystal
Computational approach predicted the formation of hydrogen bonds between quercetin and coformers used, and interaction involved minimum energy: tartaric acid (66.3288 kcal/mol), maleic acid (35.6241 kcal / mol), mannitol (1052.85 kcal/mol), lysine (53.6929 kcal/mol), arginine (85.3495 kcal/mol), saccharin (44.1072 kcal/mol), nicotinamide (41.5672 kcal/mol), and isonicotinamide (20.0104 kcal/mol)

Summary

Introduction

Quercetin is a flavonoid possesses antioxidant, anti-cancer, anti-viral, anti-obesity, anti-bacterial and anti-inflammatory properties [1,2,3,4,5]. It is classified as a class II compound according to Biopharmaceutics Classification System (BCS). Quercetin is highly soluble in ethanol, and dimethyl sulfoxide (DMSO) and sparingly soluble in water [8,9]. Co-crystals are solid that are crystalline, single phase materials composed of two or more different molecular or ionic compounds generally in stoichiometric ratios which are neither solvates nor simple salts [11]. Interactions involved in co-crystal formation are hydrogen bonds, Van der Waals forces, and π-π* interactions [12]

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