Improving the Solubility of Fenofibric Acid via Multicomponent Crystal Formation with Theobromine Coformer

Abstract

Fenofibric acid (FA) is a class II biopharmaceutical system drug, a potential drug for antihyperlipidemic. FA lowers low-density lipoprotein (LDL) and triglyceride levels and increases high-density lipoprotein (HDL). Due to its low solubility, the bioavailability of FA is also low. To overcome the undesirable effects of these biopharmaceutical properties, this study focused on improving the solubility of FA in the form of FA multicomponent crystals with theobromine (TH) coformer using solvent drop grinding as the crystallisation method. Multicomponent crystals of FA with TH coformer named FA-TH were successfully prepared. Detailed structural studies of this new solid form were carried out using powder X-ray diffraction (PXRD), Fourier Transform Infrared (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM), and hot-stage microscopy. The thermogram of the DSC test showed that the melting point of FA-TH multicomponent crystals was lower than the melting point of the forming compound. The X-ray diffraction exhibits diffraction peaks of FA-TH multicomponent crystal and superimposition between the diffraction peaks of FA and TH. Solubility of FA-TH multicomponent crystals showed improvement up 4.4-fold compared to pure FA. These results demonstrate the potential of this new solid form to improve the solubility of FA.