Quantification of gabapentin polymorphs in gabapentin/excipient mixtures using solid state 13C NMR spectroscopy and X-ray powder diffraction

Gabapentin was used as a model pharmaceutical compound with susceptibility to polymorphic transformation as a function of environmental and mechanical stress. The utility of C-13 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 C-13 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 C-13 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 C-13 CP/MAS NMR spectra and environmentally-controlled XRPD were devised to determine polymorphic transformation kinetics of co-milled excipient mixtures during storage. (C) 2017 Elsevier B.V. All rights reserved.