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.
A continuous Couette-Taylor (CT) crystallizer exploiting a Taylor vortex was developed to promote the phase transformation of guanosine 5-monophosphate (GMP). In drowning-out crystallization, amorphous GMP is initially generated and then transformed into hydrate GMP crystals via the consecutive dissolution of the amorphous GMP and nucleation and growth of hydrate GMP crystals. Because of the intensive mixing of the Taylor vortex, the dissolution of the amorphous GMP and growth of the hydrate GMP crystals were both markedly promoted, allowing the phase transformation to be completed within a mean residence time of 5 min, even with a high GMP feed concentration of 150 g/L and moderate rotation speed of 300 rpm This result was at least 5 times faster than the phase transformation in a mixed suspension, mixed product removal (MSMPR) crystallizer under the same crystallization conditions. The phase transformation efficiency of the Taylor vortex over the turbulent eddy in the MSMPR crystallizer was explained in terms of the effectiveness of the turbulence for the mass transfer at the solid-liquid interface.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.