Solubility Measurement of Crystal Form II and Form V Ticagrelor in Several Pure Organic Solvents

Ticagrelor (TCG) is a P2Y12 platelet inhibitor and has several crystal forms including Form II and Form V. In this work, it has been confirmed that Form II TCG would gradually transform to Form V in selected solvents. According to the crystal form stability, a dynamic method was adopted to measure the solubility of Form II TCG in six pure solvents (n-propanol, isopropanol, n-butanol, 2-butanol, ethyl acetate, and isopropyl acetate). The solubility of Form V TCG in 12 pure solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, 2-butanol, methyl acetate, ethyl acetate, isopropyl acetate, acetone, 2-butanone, and cyclohexanone) was measured by a static method. The solubility measurement temperature range was from 273.15 to 313.15 K. The experimental solubility data were correlated by the modified Apelblat model and the λh model. It was shown that the calculated solubility was consistent with the experimental data.