Novel Cocrystal of Quercetagetin: In vitro and in vivo Insights into Biopharmaceutical Performance

Purpose: Quercetagetin (QTGN) is a naturally occurring flavonol predominantly sourced from marigold flowers and possesses notable therapeutic potential, including antidiabetic, Anticancer, antioxidant, anti-inflammatory, and Antiviral properties. However, poor aqueous solubility and in turn bioavailability restrict therapeutic utility of QTGN. Crystal engineering is one of the approaches proven to be fruitful in resolving the solubility issues of many active pharmaceutical ingredients (APIs).

Method: In the present work, a cocrystal of QTGN using betaine (BET) as coformer viz. Quercetagetin⋅betaine⋅ethanol (QTGN⋅BET⋅EtOH) was synthesized using the solvent evaporation method. It was further characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TGA), Powder X-ray diffraction (PXRD), and single crystal XRD (SCXRD).

Result: FTIR studies confirmed hydrogen bonding between QTGN and BET. PXRD studies showed formation of new crystalline phase. The prepared cocrystal had stoichiometric ratio of 1:1:1 between QTGN, BET, and ethanol forming cocrystal ethanolate and shared robust hydroxyl⋯carboxylate supramolecular synthon as confirmed by TGA and SCXRD, respectively. Equilibrium solubility study and in vitro dissolution study showed a significant improvement (p < 0.0001) in aqueous solubility of QTGN upon its cocrystallization with BET. Furthermore, in vivo pharmacokinetic study revealed a 1.28-fold increase in bioavailability of QTGN when formulated as cocrystal solvate. The prepared cocrystal was found to be stable over a period of six months at 40°C and 75% RH when analyzed using PXRD studies.

Conclusion: The current work represents a frontier in pharmaceutical formulation, providing a means to fully harness the therapeutic potential of QTGN using cocrystal approach.

USP apparatus IV; betaine; bioavailability; cocrystal; quercetagetin.