Abstract

Pharmaceutical compounds having the ability to form different solid forms can influence the physical, chemical and mechanical properties of a drug. It is important to have sufficient knowledge regarding the thermodynamic landscape of these solid forms and their transformation mechanisms in different conditions, because uncontrolled solid form transformations have been shown to be a root-cause of many product withdrawals. The aim of this study was to obtain molecular level insight into the phase transformation of nitrofurantoin monohydrate (NF MH II) to the stable anhydrous form using a Polytec® vibrometer. Method: Single crystals of nitrofurantoin monohydrate (NF MH II) were used as a model particles. The MH form of NF was identified using DSC, TGA, XRPD, and compared to the Cambridge Structural Database (CSD). Single crystal dehydration of NF MH II was monitored using a Linkam hotstage (2°C/minute) and a Polytec® vibrometer. Results: All solid-state analytical methods used confirmed the solid state form of NF to be NF MH II (CSD ref code: HAXBUD). The first two modes of vibration from NF MH II were detected at 35.16 kHz and 83.91 kHz. The Polytec® vibrometer could detect the phase transition at around 120°C for NF MH II. It was sensitive enough to detect nucleation on particular sites of the single crystal (NF MH II) and potentially track the metastable anhydrous (alpha) form of nitrofurnatoin. Conclusion: The thermomechanical data was in agreement with the literature and show the potential to obtain a more detailed understanding about hydrate-anhydrate phase transformations.