A study of the heat-mediated phase transformations of praziquantel hydrates. Evaluation of their impact on the dissolution rate
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Elsevier
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Comprehensive knowledge of the critical properties of the active pharmaceutical ingredients is a requirement
within the modern concept of quality. Praziquantel hemihydrate (HH) and monohydrate (MH) are new solid
forms of this antihelmintic agent, which have better solubility properties than the commercial anhydrous solid
form (polymorph A). The thermal stability of the hydrates was evaluated, aiming to understand any possible
transformation (amorphization, change to a less soluble form).
Therefore, HH and MH were prepared along with the related anhydrous solid forms A and B, and characterized
employing solid-state nuclear magnetic resonance, powder X-ray diffraction, mid and near infrared spectroscopy,
thermal methods and the intrinsic dissolution rate.
The transformations of HH and MH under thermal stress conditions were monitored through a variable temperature infrared spectroscopy approach, assisted by multivariate curve resolution with alternating least squares
(MCR-ALS), finding that HH undergoes a two-step transformation (HH→B→A) to form A, whereas MH dehydrates
directly into form A. This was further confirmed by conventional calorimetric methods (differential scanning
calorimetry and thermogravimetry) and powder X-ray diffractometry.
The impact of changes in the stressed solid forms and their dissolution rates was also assessed. Significant
differences in dissolution performance were found regarding the solid forms produced as a consequence of
thermally-induced dehydration.
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