Modifications evaluation of ethyl para methoxycinnamate crystal with enhanced solubility properties by solvent-mediated polymorphism and multicomponent interactions

Ethyl p-methoxycinnamate (EPMC) is the primary chemical extracted from the rhizome of aromatic ginger (Kaempferia galanga L.) that has been shown to have various beneficial pharmacological actions for the body; nevertheless, when used as an oral preparation, it has limited water solubility. As a pharmaceutical raw material, it is vital to investigate which form has the most potential as the best ingredient in pharmaceutical dosage forms. In this work, the crystal habit of EPMC was created by solvent-mediated polymorphism and coformer alteration with various pKa variations. Their interaction was modeled using an in silico test.  Through these two approaches, the EPMC solubility was increased to a higher level. The results show that increasing solubility may be accomplished optimally by polymorphism modification with non-polar solvent such as n-hexane (0.202 mg/mL) and co-crystal formation with succinic acid as coformer (0.217 mg/mL). All characterized crystal habits determined by polarization microscopy, Fourier Transform IR, Differential Scanning Calorimetry, and pKa calculations revealed that all crystal modifications have different properties, with cocrystal formation using succinic acid as a coformer providing the greatest solubility. The best solubility results from both techniques were obtained in the form of the co-crystalline form of EPMC-succinic acid with 36.5% improve over the initial solubility.