Patel Mayank, Hirlekar Rajashree
Department of Pharmaceutics, Bharati Vidyapeeth's College of Pharmacy, Sector-8, C.B.D. Belapur, Navi Mumbai 400614, Maharashtra, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai 400019, India.
Asian J Pharm Sci. 2019 Jan;14(1):104-115. doi: 10.1016/j.ajps.2018.02.007. Epub 2018 Mar 13.
The purpose of the present study was to investigate the interaction of Cinnarizine (CIN) with Hydroxypropyl-β-Cyclodextrin (HPβCD) in the presence of Hydroxy Acids (HA). Various binary and ternary systems of CIN with HPβCD and HA were prepared by kneading and coevaporation methods. For the ternary systems, HA were tried in three different concentrations. The interaction in solution phase was studied in detail by the phase solubility method, and the solid phase interactions were characterized by Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance (H-NMR). Phase solubility revealed the positive effect of HA on the complexation of CIN with HPβCD. Solid phase characterization confirmed the formation of inclusion complex in the ternary systems. Solubility and dissolution studies illustrated that out of three different concentrations tried, HA were most effective at the 1 M concentration level. Ternary systems were very effective in improving the solubility as well as dissolution profile of CIN than the CIN-HPβCD binary systems. FTIR, H-NMR and Molecular docking studies gave some insight at molecular level that actually which part of CIN was interacting with the HPβCD. Molecular docking and free energy calculation even enlighten the role of tartaric acid in increasing solubility of CIN in the ternary system.
本研究的目的是研究在羟基酸(HA)存在下桂利嗪(CIN)与羟丙基-β-环糊精(HPβCD)的相互作用。通过捏合和共蒸发法制备了CIN与HPβCD和HA的各种二元和三元体系。对于三元体系,尝试了三种不同浓度的HA。通过相溶解度法详细研究了溶液相中的相互作用,并通过傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)、X射线衍射法(XRD)、扫描电子显微镜(SEM)和质子核磁共振(H-NMR)对固相互作用进行了表征。相溶解度揭示了HA对CIN与HPβCD络合的积极作用。固表征证实了三元体系中包合物的形成。溶解度和溶出度研究表明,在尝试的三种不同浓度中,HA在1 M浓度水平时最有效。与CIN-HPβCD二元体系相比,三元体系在改善CIN的溶解度和溶出度方面非常有效。FTIR、H-NMR和分子对接研究在分子水平上提供了一些见解,即CIN的哪一部分实际上与HPβCD相互作用。分子对接和自由能计算甚至揭示了酒石酸在提高三元体系中CIN溶解度方面的作用。