Co-crystalization of quercetin and malonic acid using solvent-drop grinding method
Purpose: To determine the physicochemical properties and in vitro dissolution profile of quercetinmalonic acid co-crystals prepared using solvent-drop grinding method.
Methods: Co-crystallization of quercetin (Q) and malonic acid (MA) in molar ratios of 1:1 (CC1) and 1:2 (CC2) was performed by solvent-drop grinding method with addition of 20 % (w/v) ethanol in a shaker mill run for 30 min. The co-crystal phase was characterized by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), scanning electron microscopy (SEM), and fourier transform infrared (FT-IR) spectroscopy. In vitro dissolution was performed using the paddle method at 100 rpm in the medium of citrate buffer (pH 5.0 ± 0.05) containing 2.0 % (w/v) sodium lauryl sulfate at 37 ± 0.5 °C.
Results: Thermograms from DSC showed that CC1 and CC2 co-crystals had endothermic peaks at 283.02 and 266.61 °C, respectively. These peaks were in-between the melting points of Ma and Q. The powder diffractogram of CC1 showed new diffraction peaks at 16.21, 19.87, and 28.88 °, while CC2 showed new ones at 16.18, 19.86, and 28.83 °. There were OH- band shifts in IR spectra from 3411 to 3427 cm-1 for CC1, and from 3411 to 3466 cm-1 for CC2. Images from SEM indicate that the crystal habits and morphologies of the co-crystals differed from those of the original components. The dissolution efficiency of CC2 increased 1.056 times relative to pure Q.
Conclusion: Co-crystal phase of Q and MA prepared using solvent-drop grinding (CC1 and CC2) displays physicochemical characteristics different from those of the physical mixtures and their pure components. There is an increase in vitro dissolution as a result of co-crystal formation.
Keywords: Co-crystal, Dissolution, Malonic acid, Quercetin, Solvent-drop grinding