Varma Abhishek, Laxmi Prasanna, Pai Aravind, Pai Girish, Sg Vasantharaju, Badamane Sathyanarayana Muddukrishna
Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences (MCOPS).
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences (MCOPS).
Chem Pharm Bull (Tokyo). 2019;67(8):816-823. doi: 10.1248/cpb.c19-00202.
In this present study a new co-crystals of zoledronic acid with DL-tartaric acid and nicotinamide has been developed with improved solubility. Zoledronic acid is a class III drug with poor oral bioavailability due to its poor permeability and low aqueous solubility; hence an attempt has been made to improve its solubility by co-crystallization technology. Pharmaceutical cocrystals are multi-component crystals with a stoichiometric ratio of active pharmaceutical ingredients (APIs) and cocrystal coformers (CCFs) that are assembled by noncovalent interactions such as hydrogen bonds, π-π packing, and Vander Waals forces. In this study the coformers selected were DL-tartaric acid and nicotinamide based on ease of hydrogen bond formation. The co-crystal of zoledronic acid with DL-tartaric acid were prepared in three ratios (1 : 1, 1 : 2 and 2 : 1) by slow solvent evaporation method and with nicotinamide in 1 : 1 ratio by dry grinding method. The formation of co-crystal was confirmed by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier transform (FT)IR. The dynamic solubility of co-crystals with DL-tartaric acid in the ratios 1 : 1, 1 : 2 and 2 : 1 increased by fold as compared to pure drug.
在本研究中，已开发出唑来膦酸与DL-酒石酸和烟酰胺的新型共晶体，其溶解度有所提高。唑来膦酸是一种III类药物，由于其渗透性差和水溶性低，口服生物利用度不佳；因此，已尝试通过共结晶技术提高其溶解度。药物共晶体是由活性药物成分（API）和共晶体共形成剂（CCF）按化学计量比组成的多组分晶体，它们通过氢键、π-π堆积和范德华力等非共价相互作用组装而成。在本研究中，基于易于形成氢键的原因，选择的共形成剂为DL-酒石酸和烟酰胺。唑来膦酸与DL-酒石酸的共晶体通过缓慢溶剂蒸发法以三种比例（1∶1、1∶2和2∶1）制备，与烟酰胺的共晶体通过干磨法以1∶1的比例制备。通过粉末X射线衍射（PXRD）、差示扫描量热法（DSC）和傅里叶变换红外光谱（FT）IR确认了共晶体的形成。与纯药物相比，唑来膦酸与DL-酒石酸比例为1∶1、1∶2和2∶1的共晶体的动态溶解度成倍增加。
