Polymorphic and pseudomorphic transformation behavior of acyclovir based on thermodynamics and crystallography

Acyclovir (ACV) has two polymorphs, anhydrate 1 and anhydrate 2, and two hydrates, 2/3 hydrate and dihydrate. The effect of polymorphic transformation of ACV on the temperature and humidity was evaluated by simultaneous XRD-DSC and vapor sorption analysis. Each crystal structure of ACV was analyzed by single crystal analysis and powder X-ray diffraction analysis. On the polymorphic and pseudomorphic transformation, anhydrate 1 did not directly transform to anhydrate 2, but transform through 2/3 hydrate and dihydrate due to relative humidity and temperature. According to the molecular packing for four crystals, there are two packing manners for purine moiety. Anhydrate 1, anhydrate 2, 2/3 hydrate and dihydrate were packed in parallel, anti parallel, mixture of parallel–anti parallel and parallel manners, respectively. Base on the packing manner of ACV, it can be seen why the phase transformation occurs with readily or with difficulty. The thermodynamic relation of anhydrate form 1 and form 2 was evaluated by DSC and microcalorimetry. It was found that these two forms are monotropic forms, with anhydrate form I is stable form and it transform to a new form 3 at 443.2 K.