Cocrystallization is one of the potent methods used to modify the physicochemical properties of drugs. Cocrystal of nicotinamide (NIC):p-coumaric acid (COU) was synthesized by a slow evaporation method using acetonitrile. The cocrystals with different feed molar ratios (NIC:COU : 1:1, 1:2, and 2:1) were characterized using DSC, PXRD, and FTIR, which revealed the formation of different polymorphs for each feed molar ratio. A single crystal of the NIC:COU (1:1) cocrystal was analyzed using single crystal X-ray diffraction (SCD), and 1H-NMR revealed a greater cocrystal structure stability compared to the previously published cocrystal. The intermolecular hydrogen bonds, N-H···O, and O-H···O interactions played a major role in stabilizing the cocrystal structure. A molecular modeling technique was used for prediction and surface chemistry assessment of the morphology showed an elongated (along y-axis) octagonal crystal shape which was in a reasonable agreement with the experimental crystal morphology. The reduction in values of the cocrystal solubility in ethanol was supported by the DSC data and simulation of crystal facets where most the crystal facets exposed to polar functional groups. At the concentration of 31.3 µM, NIC:COU (1:1) cocrystal showed more effective DPPH scavenging with 77.06% increased activity compared to NIC at the same concentration.
Cocrystal plays an important role in the pharmaceutical industry to improve the low solubility and bioavailability of drugs. In this study, the cocrystal formation screening was carried out for nicotinamide(NIC) as the API (Active Pharmaceutical Ingredient) with two coformers; cinnamic acid (CIN), and p-coumaric acid (COU) using recrystallization method with different solvents (methanol, ethanol, and acetonitrile) and molar ratios of NIC:CIN and NIC:COU of 1:1, 1:2 and 2:1. The NIC:CIN and NIC:COU mixtures were characterized using Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier Transform Infrared (FTIR) to assess the formation of cocrystal. All characterization data for NIC:CIN mixtures showed that the use of different types of solvents and molar ratios have no significant effect on the formation of the cocrystal. The characterization data showed the formation of similar NIC:CIN cocrystal with no polymorphism with a melting temperature of 96–98 oC for all mixtures. The diffraction pattern of all NIC:CIN also showed similar new peaks at 2θ of 6.7°, 17.7°, 20.6°, 22.4°, and 25.1°. The DSC and PXRD data of NIC:CIN were supported by FTIR which revealed similar hydrogen bonding interaction for all NIC:CIN mixtures. The characterization of NIC:COU mixture revealed four different cocrystal forms with melting points of 118 °C, 152 °C, 160 °C, and 169 °C. The PXRD data of NIC:COU mixture also showed different diffraction patterns signifying distinct crystalline identities which supported with different FTIR spectrum validating the difference in hydrogen bonding interaction. It was observed that the use of different types of solvents did not give significant effects on the formation of NIC:CIN and NIC:COU cocrystals. Keywords: Nicotinamide, Cocrystal Pre-Characterization, DSC, PXRD, FTIR
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