Establishment of a cocrystal characterization method for sacubitril valsartan sodium / 药学学报

Sacubitril valsartan sodium (LCZ696) is an ionic cocrystal drug. The purpose of this study was to explore the cocrystal features of LC696 by establishing a variety of characterization methods, and thus provide basic research data for effective quality control. The cocrystal characteristics of LCZ696 and its tablets were identified by applying analytical means including powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), Raman spectra (RM), differential scanning calorimetry (DSC) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). The crystalline water and hygroscopicity of LCZ696 were analyzed by thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), hygroscopicity test and Karl Fischer reaction method. The results show that PXRD, FTIR, DSC and ssNMR can effectively distinguish the features of LCZ696 cocrystal, sacubitril monomer, valsartan monomer, and sacubitril-valsartan (1∶1) mixture. RM can be used as a supplementary approach. Combined with the analysis by TGA, DVS, hygroscopicity test and Karl Fischer reaction method results, LCZ696 contains 2.5 crystalline water molecules and is very hygroscopic; we recommend that LCZ696 be stored in an environment with a relative humidity below 60%. By characterizing the crystal features we can establish quality control measure and evaluate the stability of the drug tablets. This study provides data in support for the establishment of the LCZ696 quality standard.

Production of Cellulose and Profile Metabolites by Fermentation of Glycerol by Gluconacetobacter Xylinus

ABSTRACT Because of the widespread occurrence of cellulose in nature, many organisms use glycerol as a source of carbon and energy, so these organisms have drawn attention to the potential use of glycerol bioconversion. The bacteria Gluconacetobacter xylinus, a strictly aerobic strain that performing incomplete oxidation of various sugars and alcohols to cellulose biosynthesis. For this reason, we modify the Hestrim-Schram medium, associating glycerol, glucose and sucrose varying their concentration. The fermentations were performed statically at a temperature of 28˚C for a period of 10 days. The pH, membrane formation, crystallinity and the production of some metabolites of the 4th, 7th and 10th days was evaluated. The results showed a higher yield of membrane in the medium containing glucose, gly 1 + glu2 on 10 fermentation of 3.5 g %. Through solid-state NMR gave the crystallinity of the membranes, where there was a clear trend toward higher crystallinity membranes with 7 days of fermentation. Metabolic products found in the media by analysis of NMR spectroscopy in liquid were similar, especially for the production of alanine and lactate that were present in all media. The leucine and threonine were present in various media, although in small quantities has been found glutamate.

Crystal form identification of dasatinib in tablets / 中国药科大学学报

The aim of this study was to establish the methods to identify crystal form of dasatinib in tablets.X-ray powder diffraction(XRPD)and solid-state nuclear magnetic resonance(ssNMR)were used to analyze the crystal form of dasatinib in Sprycel? tablets and Yinishu? tablets.The results showed that monohydrate and anhydrate were identified in Sprycel? and Yinishu? tablets respectively;with no detectable anhydrate in Sprycel? tablets and no detectable monohydrate in Yinishu? tablets.The results of XRPD and ssNMR were consistent;and could be both applied in the crystal form identification of dasatinib in tablets.