Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA, 52242, USA.
Department of Chemistry, The University of Iowa, Iowa City, IA, 52242, USA.
J Pharm Biomed Anal. 2017 Nov 30;146:29-36. doi: 10.1016/j.jpba.2017.07.048. Epub 2017 Aug 5.
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 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 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 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 39mol%, respectively. A quenching procedure for obtaining C CP/MAS NMR spectra and environmentally-controlled XRPD were devised to determine polymorphic transformation kinetics of co-milled excipient mixtures during storage.
加巴喷丁被用作模型药物化合物，其对多晶型转变的易感性是环境和机械应力的函数。研究了 C CP/MAS NMR 和 XRPD 作为稳定性指示方法来定量多晶型转变动力学的实用性。基于化学位移和不同衍射峰的差异，可以区分 II 型和 III 型多晶型。使用 C CP/MAS NMR 光谱和 XRPD 图谱中的信号，证明了在存在选定赋形剂的情况下，对多晶型组成进行可重复且准确的定量。通过共研磨后测量转化来确定赋形剂对多晶型转变（II 型→III 型）的影响。C CP/MAS NMR 和 XRPD 都能够在没有赋形剂峰干扰的情况下测量共研磨赋形剂混合物中的多晶型组成。含有胶体二氧化硅、淀粉、羟丙基纤维素和磷酸氢钙的共研磨混合物中 III 型的含量分别为 8.7、21、33 和 39mol%。设计了一种淬火程序来获得 C CP/MAS NMR 光谱和环境控制的 XRPD，以确定储存期间共研磨赋形剂混合物的多晶型转变动力学。
