Szeleszczuk Łukasz, Pisklak Dariusz Maciej, Zielińska-Pisklak Monika, Wawer Iwona
Faculty of Pharmacy with The Laboratory Medicine Division, Medical University of Warsaw, Department of Physical Chemistry, Banacha 1, 02-093 Warsaw Poland.
Faculty of Pharmacy with The Laboratory Medicine Division, Medical University of Warsaw, Department of Physical Chemistry, Banacha 1, 02-093 Warsaw Poland.
Int J Pharm. 2017 Aug 30;529(1-2):193-199. doi: 10.1016/j.ijpharm.2017.06.078. Epub 2017 Jun 27.
Diosmin, a flavone glycoside frequently used in therapy of various veins diseases in monohydrate form, exhibits poor solubility in water and low bioavailability. Due to the fact that the anhydrous forms of drugs generally have better bioavailability than the corresponding hydrates, the aim of this study was to analyze the conversion of diosmin monohydrate (DSNM) to anhydrous diosmin (DSNA) that occurs upon heating. The mechanism of this transformation was examined as well as advanced structural studies of each form were performed using 13C CP/MAS SSNMR, DSC, FT-IR and PXRD techniques. Spectroscopic findings were supported by CASTEP-DFT calculations of NMR and IR parameters. The pathway of reversible transformation was specified as follows: DSNM upon heating for 24h at temperature up to 110°C losses non-crystalline water and converts into metastable form (DSNM*) that turns into DSNA during heating at temperature 140°C for next 24h. Under room temperature DSNA spontaneously absorbs moisture from air and turns into a DSNM within 72h. The detailed analysis of CP kinetic parameters (T1ρI) revealed presence of metastable, intermediate form of diosmin (DSNM*) and allowed its characterization. The results are essential for further studies comparing dissolution and bioavailability of DSNM and DSNA. The study provided an understanding of the conversion pathway of the diosmin monohydrate into its anhydrate form when it is exposed to increased temperature.
地奥司明，一种常以一水合物形式用于治疗各种静脉疾病的黄酮苷，在水中溶解度差且生物利用度低。由于药物的无水形式通常比相应的水合物具有更好的生物利用度，本研究的目的是分析加热时地奥司明一水合物（DSNM）向无水地奥司明（DSNA）的转化。研究了这种转变的机制，并使用13C CP/MAS SSNMR、DSC、FT-IR和PXRD技术对每种形式进行了深入的结构研究。光谱学研究结果得到了NMR和IR参数的CASTEP-DFT计算的支持。可逆转变的途径如下：DSNM在高达110°C的温度下加热24小时会失去非结晶水，并转化为亚稳态形式（DSNM*），在接下来的140°C温度下加热24小时期间会转变为DSNA。在室温下，DSNA会自发地从空气中吸收水分，并在72小时内转变为DSNM。对CP动力学参数（T1ρI）的详细分析揭示了地奥司明存在亚稳态的中间形式（DSNM*），并对其进行了表征。这些结果对于进一步比较DSNM和DSNA的溶解和生物利用度的研究至关重要。该研究提供了对地奥司明一水合物在温度升高时转化为其无水形式的途径的理解。
