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