Investigating gabapentin polymorphism using solid-state NMR spectroscopy

Kassibla E. Dempah, Dewey H. Barich, Aditya M. Kaushal, Zhixin Zong, Salil D. Desai, Raj Suryanarayanan, Lee Kirsch, Eric J. Munson

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33 Scopus citations


Solid-state NMR spectroscopy (SSNMR), coupled with powder X-ray diffraction (PXRD), was used to identify the physical forms of gabapentin in samples prepared by recrystallization, spray drying, dehydration, and milling. Four different crystalline forms of gabapentin were observed: form I, a monohydrate, form II, the most stable at ambient conditions, form III, produced by either recrystallization or milling, and an isomorphous desolvate produced from desolvating the monohydrate. As-received gabapentin (form II) was ball-milled for 45 min in both the presence and absence of hydroxypropylcellulose (HPC). The samples were then stored for 2 days at 50 C under 0% relative humidity and analyzed by 13C SSNMR and PXRD. High-performance liquid chromatography was run on the samples to determine the amount of degradation product formed before and after storage. The 1H T 1 values measured for the sample varied from 130 s for the as-received unstressed material without HPC to 11 s for the material that had been ball-milled in the presence of HPC. Samples with longer 1H T 1 values were substantially more stable than samples that had shorter T 1 values. Samples milled with HPC had detectable form III crystals as well. These results suggest that SSNMR can be used to predict gabapentin stability in formulated products.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalAAPS PharmSciTech
Issue number1
StatePublished - 2013

Bibliographical note

Funding Information:
We are grateful to the National Institute for Pharmaceutical Technology and Education and the U.S. Food and Drug Administration (FDA) for providing funds for this research. This study was funded by the FDA-sponsored contract #HHSF223200819929C “Development of Quality by Design (QbD) Guidance Elements on Design Specifications Across Scales with Stability Considerations.” EJM is a partial owner of Kansas Analytical Services, a company that provides solid-state NMR services to the pharmaceutical industry. The results presented here are from EJM's academic work at the University of Kansas and the University of Kentucky, and no data from Kansas Analytical Services is presented here.


  • grinding
  • polymorphism
  • relaxation time
  • solid-state NMR
  • stability


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