Multicomponent Crystals of Piperine-Nicotinic Acid: The Physicochemical and Dissolution Rate Properties

Abstract

Piperine is included in Class II of the Biopharmaceutical Classification System. Piperine has low solubility in water, resulting in low bioavailability. To improve the physicochemical properties and increase the dissolution rate of piperine, multicomponent crystals were prepared by solvent-drop grinding, using ethanol pa with the addition of nicotinic acid as a coformer. The formation of multicomponent crystals was achieved by varying the mole ratios in the formulas (F): F1 (1:1), F2 (2:1), and F3 (1:2). The multicomponent crystals were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), solubility tests, and dissolution profiles using a type II paddle. The XRD patterns showed a decrease in the intensity of the multicomponent crystal formula compared to piperine and the physical mixture. The DSC thermograms showed a decrease in endothermic peaks and enthalpy values. The FTIR spectra confirmed that there was no chemical interaction between piperine and nicotinic acid. SEM analyses showed the formation of new crystal habits. The solubility tests and dissolution profiles showed a significant increase in the amount of solute from the crystalline multicomponent formula compared to intact piperine and the physical mixture. Therefore, the multicomponent piperine-nicotinic acid crystals can improve the physicochemical properties and increase the dissolution rate of piperine.