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The pharmaceutical co-crystal has attracted a lot of attention in recent years as a new direction in the research of polymorphism drugs. The research on pharmaceutical co-crystal has scientific significance for improving the solubility, bioavailability and physical or chemical stability of drugs. In this paper, from the perspective of drugs for the treatment of cardiovascular diseases(including five major types: heart failure, hypertension, coronary heart disease and arrhythmia, stroke) , the latest research results of pharmaceutical co-crystal reported in recent years are reviewed, hope to provide reference for the follow-up research and promote the development of pharmaceutical co-crystal in China.
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OBJECTIVE:To observe clinical efficacy of Felodipine sustained-release tablets(Ⅱ)in the treatment of elderly es-sential hypertension and its improvement effect on arterial elasticity,left ventricular remodeling and the quality of life. METHODS:A total of 96 elderly patients with essential hypertension in our hospital during Aug. 2014-Dec. 2015 were divided into observation group (50 cases) and control group (46 cases) according to random number table. Observation group was given Felodipine sus-tained-release tablets(Ⅱ)5 mg orally,qd,with empty stomach in the morning;control group was given Irbesartan tablets 150 mg, qd,with empty stomach in the morning. Both groups received treatment for 12 weeks. Clinical efficacies of 2 groups were observed as well as 24 h ambulatory blood pressure (ABP),indexes of arlerial elasticity [carotid-radial pulse wave velocity (CR-PWV),carot-id-femoral pulse wave velocity (CF-PWV)], indexes of left ventricular remodeling [diastolic interventricular septum thickness (IVST),diastolic left ventricular posterior wall thickness(LPWT),left ventricular end diastolic diameter(LVIDd)] before and after treatment. The physiological function (PF),social function (SF),role-physical (RP),body pain (BP),mental health (MH),role-emotional(RE),vitality(VT)and general health(GH)score of SF-36 were observed in 2 groups before and after treatment. The occurrence of ADR was compared between 2 groups. RESULTS:There was no statistical significance in total response rate be-tween 2 groups (P>0.05). There was no statistical significance in 24 hABP,CR-PWV,CF-PWV,IVST,LPWT,LVIDd,SF-36 score between 2 groups before treatment(P>0.05). After treatment,the levels of 24 hSBP,24 hDBP and 24 hMAP in 2 groups were decreased significantly,and 24 hSBP and 24 hMAP of observation groups were significantly lower than those of control group,with statistical significance (P0.05). The levels of CR-PWV,CF-PWV, IVST and LPWT in observation group were decreased significantly,and the levels of CR-PWV and LPWT in control group were also decreased significantly. The levels of CR-PWV,CF-PWV,IVST,LPWT and LVIDd in observation group were significantly lower than control group,with statistical significance (P0.05). CONCLUSIONS:Felodipine sustained-release tablets(Ⅱ)exhibit significant effect and small blood pres-sure fluctuation in the treatment of elderly essential hypertension,and can improve the quality of life with good safety.
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Objective To evaluate the polymorphism of levonorgestrel by kinds of analysis technologies, and get the preponderant pharmaceutical polymorph by in vitro assessment including the stability and solubility. Methods Three polymorphs were obtained by quick solvent removal and precipitation methods. These polymorphs were characterized by X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), Raman spectroscopy and microscope. Furthermore,the stability was studied by X-ray powder diffraction analysis technology and using the curve of solubility to evaluate the dissolution rate of the three crystal forms. Results The levonorgestrel polymorphs α,β and γ were identified. The results of stability indicated that the levonorgestrel polymorphs α and β were metastable while the levonorgestrel polymorph γ was stable,and the dissolution rate of α, β, γ decrease in turn. Conclusion The levonorgestrel polymorph α is preponderant pharmaceutical polymorph. And the research on preponderant pharmaceutical polymorph of levonorgestrel provides scientific basic data for its clinical drug evaluation and establishing the quality standards.
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Objective To establish an innovative methods for the identification of nimodipine polymorphs. Methods Nimodipine of two crystal forms were prepared by rapid solvent removal and identified by powder X-ray diffraction, infrared spectroscopy and Raman spectroscopy.The dissolution study of the powder samples were carried out in six different mediums. Results Powder X-ray diffraction patterns of crystal form A and B could be used for the identification of crystal forms of nimodipine.Crystal form B has characteristic diffraction peaks at 2θ=5° and 2θ=13° in the pattern,while crystal form A has characteristic diffraction peaks at 2θ=27° distinguishing two crystal forms effectively. Raman spectrum could be used to identify the crystal forms.Compared with Raman spectra of crystal form B, there exists characteristic scattering peak at 500 cm-1 in crystal form A. According to the position and intensity of the peaks of crystal form A and B, it could distinguish two crystal types effectively.The results of dissolution tests showed that the solubility of crystal form A is better than crystal form B. Conclusion Various analysis techniques in different principle were used in the research, such as Powder X-ray diffraction, Infrared spectroscopy and Raman Spectroscopy etc.Crystal forms were confirmed in several aspects according to the properties of different crystal form, and the solubility of crystal form A is better than crystal form B.
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Objective To establish an innovative methods for the identification of nimodipine polymorphs. Methods Nimodipine of two crystal forms were prepared by rapid solvent removal and identified by powder X-ray diffraction, infrared spectroscopy and Raman spectroscopy.The dissolution study of the powder samples were carried out in six different mediums. Results Powder X-ray diffraction patterns of crystal form A and B could be used for the identification of crystal forms of nimodipine.Crystal form B has characteristic diffraction peaks at 2θ=5° and 2θ=13° in the pattern,while crystal form A has characteristic diffraction peaks at 2θ=27° distinguishing two crystal forms effectively. Raman spectrum could be used to identify the crystal forms.Compared with Raman spectra of crystal form B, there exists characteristic scattering peak at 500 cm-1 in crystal form A. According to the position and intensity of the peaks of crystal form A and B, it could distinguish two crystal types effectively.The results of dissolution tests showed that the solubility of crystal form A is better than crystal form B. Conclusion Various analysis techniques in different principle were used in the research, such as Powder X-ray diffraction, Infrared spectroscopy and Raman Spectroscopy etc.Crystal forms were confirmed in several aspects according to the properties of different crystal form, and the solubility of crystal form A is better than crystal form B.
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Bifendate, a synthetic anti-hepatitis drug, exhibits polycrystalline mode phenomena with 2 polymorphs reported (forms A and B). Single crystals of the known crystalline form B and 3 new crystallosolvates involving bifendate solvated with tetrahydrofuran (C), dioxane (D), and pyridine (E) in a stoichiometric ratio of 1:1 were obtained and characterized by X-ray crystallography, thermal analysis, and Fourier transform infrared (FT-IR) spectroscopy. The differences in molecular conformation, intermolecular interaction and crystal packing arrangement for the four polymorphs were determined and the basis for the polymorphisms was investigated. The rotation of single bonds resulted in different orientations for the biphenyl, methyl ester and methoxyl groups. All guest solvent molecules interacted with the host molecule via an interesting intercalative mode along the [1 0 0] direction in the channel formed by the host molecules through weak aromatic stacking interactions or non-classical hydrogen bonds, of which the volume and planarity played an important role in the intercalation of the host with the guest. The incorporation of solvent-augmented rotation of the C-C bond of the biphenyl group had a striking effect on the host molecular conformation and contributed to the formation of bifendate polymorphs. Moreover, the simulated powder X-ray diffraction (PXRD) patterns for each form were calculated on the basis of the single-crystal data and proved to be unique. The single-crystal structures of the four crystalline forms are reported in this paper.
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This study compares the results of three certified methods, namely differential scanning calorimetry (DSC), the mass balance (MB) method and coulometric titrimetry (CT), in the purity assessment of ferulic acid certified reference material (CRM). Purity and expanded uncertainty as determined by the three methods were respectively 99.81%, 0.16%; 99.79%, 0.16%; and 99.81%, 0.26% with, in all cases, a coverage factor (k) of 2 (P=95%). The purity results are consistent indicating that the combination of DSC, the MB method and CT provides a confident assessment of the purity of suitable CRMs like ferulic acid.
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The determination of chemical purity of andrographolide by coulometric titration method is studied in this paper. The coulometric titration was carried out in a mixture composed of 4 mol x L(-1) hydrochloric acid and 1 mol x L(-1) potassium bromide solution and 1 mol x L(-1) potassium nitrate solution (1:1). Bromine is electrogenerated at the anode and reacts with the andrographolide. The number of electrons involved in the eleatrode reaction is 2. Purity of andrographolide is 99.76% compared with 99.77% utilizing area normalization method by HPLC. The RSD are 0.33% and 0.02% respectively. The results from two methods are consistent, so the determination of chemical purity of andrographolide by coulometric titration method is scientific and feasible. The method is rapid, simple, convenient, sensitive and accurate. The reference material is not essential in the method. The method is suitable for determination of chemical purity of andrographolide.
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Chromatography, High Pressure Liquid , Diterpenes , Electrolysis , Electrolytes , Chemistry , Indicators and Reagents , Chemistry , Linear Models , Reproducibility of ResultsABSTRACT
Objective To study the influence of Noradrenergic systems in Lateral Hypothalamus Area (LHA) on small intestine moving. Methods The effect of noradrenalin、noradrenalin+phentolamine、noradrenalin+propolol、phentolamine on small intestines electro-activity of rats was detected by external alimentary canal electrodes and central nervous system stereo-configuration technology. Results After injecting 2 g/L noradrenaline (NE) the cyclic period of MMC extended, the ratio of the active time to the cyclic period and the number of the fast wave within the active time per minute reduced. NE inhibited the electro-activity of small intestine of rats, and the average effective time was (36.86?7.39)min. Hence injecting 5 g/L PE alone to LHA raised the ratio of the MMC active time to the cyclic period. Phentolamine presented a slight excitability on the electro-activity of small intestine of rats. Conclusion The NE in LHA showed the inhibitive myoelectric activity on small intestines, and this effect was introduced through a acceptor,The reacceptor in LHA may function in the inhibition of the electro-activity in small intestines.