Quantification of gabapentin polymorphs in gabapentin/excipient mixtures using solid state 13 C NMR spectroscopy and X-ray powder diffraction
| Autor: | Kenneth R. Morris, Lee E. Kirsch, Radaduen Tinmanee, Sarah C. Larsen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Dibasic acid
Chemistry Starch Clinical Biochemistry Analytical chemistry X-ray Pharmaceutical Science Excipient 02 engineering and technology 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine 13c nmr spectroscopy Polymorphism (materials science) Drug Discovery medicine Cellulose 0210 nano-technology Spectroscopy Powder diffraction medicine.drug |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 146:29-36 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2017.07.048 |
| Popis: | Gabapentin was used as a model pharmaceutical compound with susceptibility to polymorphic transformation as a function of environmental and mechanical stress. The utility of 13 C CP/MAS NMR and XRPD as stability-indicating methods to quantify polymorphic transformation kinetics was investigated. Polymorphic Form II and III were distinguishable based on their chemical shift and distinct diffraction peak differences. Reproducible and accurate quantification of polymorphic composition in the presence of selected excipients was demonstrated using both signals from 13 C CP/MAS NMR spectra and XRPD patterns. The effect of excipients on polymorphic transformations (Form II → III) was determined by measuring the transformation after co-milling. Both 13 C CP/MAS NMR and XRPD were capable of measuring polymorphic composition in co-milled excipient mixtures without excipient peak interference. The amounts of Form III present in co-milled mixtures containing colloidal silicon dioxide, starch, hydroxy propyl cellulose and dibasic calcium phosphate were 8.7, 21, 33, and 39 mol%, respectively. A quenching procedure for obtaining 13 C CP/MAS NMR spectra and environmentally-controlled XRPD were devised to determine polymorphic transformation kinetics of co-milled excipient mixtures during storage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect