Investigating Gabapentin Polymorphism Using Solid-State NMR Spectroscopy
| Autor: | Zhixin Zong, Lee E. Kirsch, Salil D. Desai, Aditya Mohan Kaushal, Eric J. Munson, Raj Suryanarayanan, Dewey H. Barich, Kassibla Elodie Dempah |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Magnetic Resonance Spectroscopy
Cyclohexanecarboxylic Acids Analytical chemistry Pharmaceutical Science Aquatic Science Spectrophotometry Drug Discovery medicine Dehydration Amines Cellulose Chromatography High Pressure Liquid gamma-Aminobutyric Acid Ecology Evolution Behavior and Systematics Polymorphism Genetic Ecology medicine.diagnostic_test Chemistry Recrystallization (metallurgy) General Medicine Nuclear magnetic resonance spectroscopy medicine.disease Polymorphism (materials science) Solid-state nuclear magnetic resonance Spray drying Spectrophotometry Ultraviolet Gabapentin Agronomy and Crop Science Powder Diffraction Powder diffraction Research Article |
| Zdroj: | AAPS PharmSciTech. 14:19-28 |
| ISSN: | 1530-9932 |
| DOI: | 10.1208/s12249-012-9879-z |
| Popis: | 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 T1 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 T1 values were substantially more stable than samples that had shorter T1 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink