Application of Ionic Liquid to Polymorphic Design of Pharmaceutical Ingredients

This study investigated the use of an ionic liquid for designing polymorphs of the active pharmaceutical ingredient adefovir dipivoxil (AD) in drowning-out crystallization. Because of the influence of 1-ally-3-ethylimidazolium tetrafluoroborate (AEImBF4) on the formation of the intermolecular interaction of AD in the solution, new anhydrous (N-II) and hemihydrate (N-I) crystals of AD were produced when varying the ionic liquid fraction and crystallization temperature. The polymorphic structure and number of hydrate crystals were determined using X-ray diffraction and thermogravimetric analysis, respectively. Also, AEImBF4 had a significant influence on the thermal stability of the AD molecules in the AEImBF4−water mixture, as there was no hydrolysis of the AD molecules up to a temperature of 90 °C. According to a differential scanning calorimetry thermal scan, the N-I and N-II crystals were uniquely transformed into other crystal phases in a solid state. That is, the N-I crystals underwent three polymorphic changes: N-I → amorphous → form-V → liquid, while the N-II crystals underwent two polymorphic changes: N-II → form-V → liquid.