Integrated approach to study the dehydration kinetics of nitrofurantoin monohydrate.

Abstract

There is a need for thorough knowledge of solid-state transformations in order to implement quality by design (QbD) methodology in drug development. The present study was aimed at gaining a mechanistic understanding of the dehydration of nitrofurantoin monohydrate II (NF-MH). The dehydration was studied using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), and variable temperature X-ray powder diffraction (VT-XRPD). Isothermal TGA data were used to study dehydration kinetics using model-fitting and model-free approaches. Model-fitting analysis indicated a good fit for several models derived from nucleation-growth and/or geometric contraction mechanisms. However, based on visual observations during HSM, Avrami-Erofeyev equations A3 and A4, indicating nucleation-growth phenomenon, were found to be the most suitable kinetic models. HSM showed initiation of dehydration with random nucleation, and nuclei coalesced with the progress of dehydration reaction. VT-XRPD revealed formation of anhydrate beta form on dehydration of NF-MH. The phenomenon of random nucleation is justified based on the crystal structure of NF-MH, which showed presence of water molecules in an isolated manner, prohibiting directional dehydration. It was found that supplementary information from HSM and VT-XRPD can be valuable to gain a better understanding of dehydration from formal solid-state kinetics analysis.

• Authors: Vishal Koradia, Heidi Lopez de Diego, Michiel Ringkjøbing Elema, Jukka Rantanen
• Journal: Journal of pharmaceutical sciences (J Pharm Sci) Vol. 99 Issue 9 Pg. 3966-76 (Sep 2010) ISSN: 1520-6017 [Electronic] United States
• PMID: 20575054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents, Urinary
• Water
• Nitrofurantoin

Topics

• Anti-Infective Agents, Urinary (chemistry)
• Desiccation
• Kinetics
• Nitrofurantoin (chemistry)
• Powder Diffraction
• Thermogravimetry
• Water (chemistry)
• X-Ray Diffraction