Archive

• 
• 2017 Volume 48 Issue 05
  Published: 10 May 2017

    

  ---

• Select all
  |

• Select
  Applications of tert-Butanesulfinamide in the Synthesis of Chiral Amine Drugs

  ZHU Yijun, HUAN Yuliang, LENG Weidong, WU Chengxiang, WANG Bing

  2017, 48(05): 621. https://doi.org/10.16522/j.cnki.cjph.2017.05.001

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Asymmetric synthesis of chiral amine drugs based on chiral auxiliary has been extensively concerned by the scientists, tert-butanesulfinamide is a new type of chiral auxiliary developed in recent years. This review describes the applications of tert-butanesulfinamide in the synthesis of chiral amine drugs in recent years, this is significant for the synthesis of chiral amine compounds using tert-butanesulfinamide. And it confirmed that chiral auxiliaries played an important role in asymmetric synthesis of chiral drugs which would be a reference to further development of novel chiral auxiliary and its application in asymmetric synthesis.
• Select
  Progress of Tableting of Coated Pellets

  CAO Chao, LI Yang, LI Jin, TAO Tao*

  2017, 48(05): 631. https://doi.org/10.16522/j.cnki.cjph.2017.05.002

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  As a type of multiple unit dosage form, pellets has a lot of advantages in clinical application.Moreover, tablets containing pellets has been a hot area of research in industrial pharmaceutics. Some commercial products of tablets containing pellets are introduced in this paper. This kind of tablets has lots of advantages, such as improve the bioavailability, reduce the dosage and the risk of adverse drug reaction. However, the destruction of coating layer of the pellets during tableting and the segregation problem limit the wide application of tableting of coated pellets.This review summarizes the advantages and disadvantages of tablets containing pellets and discusses the key factors in tableting of coated pellets including the core of pellets, the coating materials, fillers and pharmaceutical technology.Furthermore, the progress of tableting of coated pellets and some useful information about application of this technology in industrial pharmaceutics are introduced, including new fillers, new approaches such as Wowtab® and coating excipients into pellets. Those methods are very useful for solving segregation problem and protecting coated pellets.
• Select
  Synthesis of Palbociclib

  MA Qingtong, SHAN Xiaoyan*, CHEN Xudong

  2017, 48(05): 651. https://doi.org/10.16522/j.cnki.cjph.2017.05.005

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  5-Bromouracil (3) was prepared via bromination of uracil (2) in the presence of 1,3-dibromo-5,5-dimethylhydantoin with a yield of 95％ . Then 2,4-dichloro-5 bromopyrimidine (4) was synthesized via chlorination of 3. In this step, phosphorus pentachloride was used instead of phosphoryl chloride so that the yield was increasd from 88％ to 99％ . 4 reacted with cyclopentylamine to give 5-bromo-2-chloro-N-cyclopentylpyrimidin-4-amine (5). Then 5 was subjected to Heck reaction with crotonic acid followed by lactamization to afford 2-chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one (6). In this step, palladium chloride was used instead of palladium acetate to shorten the reaction time from >36 h to 6 h and increase the yield from 80％ to >90％ . Palbociclib (1) was obtained after bromination of 6, substitution, Heck coupling reaction, acidic hydrolysis and deprotection with an overall yield of 52.1％(based on 2).
• Select
  Synthesis of the New Aminoglycoside Antibacterial Drug Plazomicin

  LIU Hanyang, ZHAO Weiwei, ZHU Xueyan, YU Xiong, WANG Hubo*

  2017, 48(05): 656. https://doi.org/10.16522/j.cnki.cjph.2017.05.006

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Plazomicin(1) was synthesized in the following steps: Sisomicin was freed from sisomicin sulfate(2), then it was selectively protected respectively with 4-nitrobenzyloxycarbonyl (PNZ) at 6'-amino group,with tert-butoxycarbonyl (Boc) at 2'- and 3-amino groups, with fluorenylmethoxycarbonyl (Fmoc) at 1-amino group,and finally with Boc at 3"-amino group to give [6'-(4-nitrobenzyloxycarbonyl)-2',3,3"-tri-tert-butoxycarbonyl-1-fluorenylmethoxycarbonyl]sisomicin (6). 6 was subjected to deprotection of Fmoc-group, condensation with N-tertbutoxycarbonyl-4-amino-2(S)-hydroxybutyric acid(12), and deprotection of PNZ-group to afford [2',3,3"-tri-tertbutoxycarbonyl-1-[N-tert-butoxycarbonyl-4-amino-2(S)-hydroxybutyryl]]sisomicin (9), 9 reacted with benzoyloxyacetaldehyde (13) via reductive amination to give [6'-benzoyloxyethyl-2',3,3"-tri-tert-butoxycarbonyl-1-[N-tertbutoxycarbonyl-4-amino-2(S)-hydroxybutyryl]]sisomicin (10). Then 10 was deprotected to give [6'-hydroxyethyl-2',3,3"-tri-tert-butoxycarbonyl-1-[N-tert-butoxycarbonyl-4-amino-2(S)-hydroxybutyryl]]sisomicin (11), afterdeprotection of Boc-group, plazomicin (1) was obtained with an overall yield of 3.8％ (based on 2). 10 and 11 are newcompounds which have not yet been reported in literature.
• Select
  Synthesis of Pyragrel Sodium

  ZHANG Qiang, LIU Weizhong*, HE Guangwei

  2017, 48(05): 662. https://doi.org/10.16522/j.cnki.cjph.2017.05.007

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  2,3,5,6-Tetramethylpyrazine (2) reacted with m-CPBA via oxidation completely to give 2,3,5,6-tetramethylpyrazinemono-N-oxide (3) with a yield of 93.5％ . Then 3 was subjected to Boekelheide reaction,hydrolysis and chlorination to afford 2-chloromethyl-3,5,6-trimethylpyrazine (6). 6 reacted with ethyl ferulate (7) via condensation to prepare ethyl (E)-3-[3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]phenyl]acrylate (8). When the reaction was finished, the product 8 could be precipitated just by adding water in a yield of 98.6％ . Then pyragrel sodium (1) was obtained after hydrolysis of 8 and salification with a purity of 99.7％ and an overall yield of 34.2％ (based on 2). 1 is a new generation of thromboxane synthetase inhibitor, which is found by the author and in phase Ⅱ clinical trail currently.
   
• Select
  Risk Assessment and Design Space Exploration of Coating Process for Esomeprazole Magnesium Enteric-coated Pellets

  LU Yaoru, DING Yu, LIU Xiaohai, WANG Yuxing, HAN Hailing*

  2017, 48(05): 673. https://doi.org/10.16522/j.cnki.cjph.2017.05.010

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  The design space of coating process for esomeprazole magnesium enteric-coated pellets was established through the risk assessment within the framework of quality by design (QbD), where the Eudragit® acrylic polymer and bottom spray technology of the fluidized bed were utilized. The pellets yield and drug release were identified as the critical quality attributes (CQAs); As well as the inlet air volume, product temperature, spray rate and atomization pressure of coating fluid were identified as the critical process parameters (CPPs). The uniform design was used to investigate the effects of these factors and their levels on CQAs. The correlation equations of CQAs and CPPs were established based on the quadratic response surface regression model, in which the R-squared values were 0.999 7 and 1.000 0, the P values were less than 0.05, respectively. Two dimensional (2D) contour plots were used to visualize the effects of CPPs and their levels on the two CQAs, respectively. Afterwards, the design space of CPPs was constructed with the addition of 95％ confidence interval. The validated results within the design space indicted that the product quality was well controlled and the robustness and flexibility of the coating process had been demonstrated.
• Select
  Preparation and in vitro Release of Artemether Nanostructured Lipid Carriers

  SHI Guangyu, WANG Xiaolei, WANG Ruili, ZHANG Shuqiu*

  2017, 48(05): 699. https://doi.org/10.16522/j.cnki.cjph.2017.05.013

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  In the present study, the formulation composition and process parameters of artemether nanostructured lipid carriers (AM-NLCs) for injection were screened and optimized. Preliminary screening was carried out through pseudo-ternary phase diagram method, then the AM-NLCs were prepared by micro-emulsion (ME) method and high pressure homogenization (HPH) method, respectively. Optimal parameters for formulation and process of both methods were obtained through single-factor test and orthogonal design with particle size and encapsulation efficiency as the indexes. The morphology, size distribution, ζ potential of AM-NLCs were characterized by transmission electron microscopy and laser light scattering method, respectively. For the AM-NLCs made by optimized ME and HPH methods, the particle size were (30.0±2.3) and (61.5±1.9)nm, the z potential were (-40.9±1.1) and (-28.4±0.5)mV, and the encapsulation efficiency were (92.8±2.4)％ and (83.8±0.2)％, respectively. The in vitro release behaviors of both AMNLCs were fitted to the first order kinetic equation. The cumulative amount of the drug release from the AM-NLCs made by the optimized ME and HPH methods were 45.8％ and 64.8％ within 12 h and 80.6％ and 83.9％ within 48 h, respectively. Both AM-NLCs showed sustained-release profiles and possessed desirable particle sizes (<80 nm). But HPH method had more stable process parameters and was more suitable for quantity production, which would be employed for AM-NLC preparation in further study.
• Select
  Optimization and Preliminary Evaluation of Liposomes Loaded with RGD Peptide

  WANG Siming1, YIN Yiqiu2, ZHANG Pengfei1, SUN Tianxia1, QI Bin1*

  2017, 48(05): 706. https://doi.org/10.16522/j.cnki.cjph.2017.05.014

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  The purpose of the study is to investigate the factors influencing the preparation of RGD peptide liposomes. The optimum conditions were determined by orthogonal test. The properties of entrapment efficiency, stability and in vitro release were investigated. The RGD liposomes were prepared by reverse phase evaporation method. The formulation and process parameters of the liposomes were optimized by single factor test and orthogonal design with entrapment efficiency as the index. The optimal conditions were as follows: the mass ratio of lecithin to cholesterol was 4 ∶ 1, the volumn of phosphate buffer (PBS) was 10 ml, the amount of RGD (Arg-Gly-Asp) peptide was 18 mg and the ultrasound time was 3 min. The average diameter and entrapment efficiency of three batches of the optimal RGD peptide liposomes were 473 nm and 75.35％ . The cumulative release of RGD peptide from the liposomes at 16 h in PBS were 48.5％ , demonstrating certain sustained-release effect compared with the RGD peptide solution. The results of preliminary stability test showed that the RGD peptide liposomes stored at 4 ℃ were rather stable.
• Select
  Determination of Gefitinib by Two Methods of Quantitative Nuclear Magnetic Resonance

  HAO Haijun, JIA Youzhi, HAN Ru*, HU Bin

  2017, 48(05): 711. https://doi.org/10.16522/j.cnki.cjph.2017.05.015

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Proton nuclear magnetic resonance (1H NMR) and fluorine nuclear magnetic resonance (19F NMR) were employed for the determination of gefitinib. 1H NMR spectra were collected at 300 K with a 8 012 Hz spectral width, 4.01 s acquisition time, 20 s relaxation delay, 9.54 μs pulse width and 64 scanning times. 19F NMR spectra were obtained by zgfhigqn.2 pulse sequence at 300 K with the internal standard of 4-bromo-2-fluoroacetanilide. Their methodologies were validated. The results of both 1H NMR and 19F NMR were generally consistent with that of the mass balance method. The established methods were specific, rapid and accurate, and were suitable for the quantitative determination of gefitinib.
• Select
  Determination of Valsartan Particle Size by Laser Light Scattering Method

  GENG Zhipeng, JIANG Yingyan, LI Yongdong, YANG Haixia*

  2017, 48(05): 716. https://doi.org/10.16522/j.cnki.cjph.2017.05.016

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  A laser light scattering method was established for the determination of particle size distribution of valsartan. A Malvern Mastersizer 2000 type laser size analyzer and a HYDRO 2000MU type wet auto sampler were used. 2％ SDS was used as the dispersion agent. The determination conditions were determined as sample refractive index of 1.53, sample absorbency of 0.01, shading degree of 8％—20％, ultrasonic treatment for 30 s, pump speed of 1 800 r/min, and measurement for 5 times. The RSDs for d(0.5) values was lower than 3％, and for d(0.1) and d(0.9) values were lower than 5％. Valsartan is almost insoluble in water, the particle size directly affects the dissolution rate of the preparation. This method is suitable for the determination of the particle size distribution of valsartan.
• Select
  HPLC Fingerprint of Yinqiaosan Ultrafine Powder and Quantitative Determination of Multi-component Indexes

  WANG Hongfeng, YIN Chou, ZHANG Min, MENG Xiaoxia, GAO Xiuli*

  2017, 48(05): 720. https://doi.org/10.16522/j.cnki.cjph.2017.05.017

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  The HPLC fingerprint of Yinqiaosan ultrafine powder was established. Meanwhile, the contents of five kinds of index components, chlorogenic acid, forsythoside A, glycyrrhizin, forsythin and arctiin, were determined as well. A Diamonsil C18 column was used, with the mobile phase of acetonitrile∶0.2％ phosphoric acid for gradient elution, at the detection wavelength of 230 nm. Ten batches of samples were analyzed by Chinese medicine fingerprint similarity
  evaluation system (2.0 edition), and a total of 33 chromatographic peaks were identified. Their similarities were all above 0.971. The calibration curves of these five index components were all with good linearity in their corresponding ranges. The average recoveries were 98.25％, 99.48％, 101.32％, 99.79％ and 99.15％, with RSDs of 1.15％, 0.87％,1.42％, 1.98％ and 0.94％, respectively. The results showed that the method is fast, simple, high precision and good reproducibility, which can provide a reliable basis for the quality control and application of Yinqiaosan ultrafine powder.
• Select
  Determination of Benzoic Acid, Sorbic Acid and Saccharin Sodium in Oral Liquid Preparations of Chinese Medicine by Hollow Fiber Centrifugal Ultrafiltration-HPLC

  LIU Yan1, NI Meiping2, LIU Ruisi1, Lü Tao1, JIANG Ye1*

  2017, 48(05): 726. https://doi.org/10.16522/j.cnki.cjph.2017.05.018

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  A hollow fiber centrifugal ultrafiltration (HF-CF-UF)-HPLC method was established for the determination of benzoic acid, sorbic acid and saccharin sodium in three kinds of oral liquid preparations of Chinese Medicine. A hollow fiber based centrifugal ultrafiltration pretreatment procedure was applied for the purification of samples. A Diamonsil C18 column was used, with the mobile phase of methanol∶0.02 mol/L ammonium acetate solution (6∶94), at the detection wavelength of 230 nm. The calibration curves of benzoic acid, sorbic acid and saccharin sodium were linear in the range of 0.5—100 μg/ml. Their average recoveries were 97.8％, 98.5％ and 97.8％, with RSDs no more than 1.7％. This method is simple and rapid, and could provide reference for the determination of benzoic acid, sorbic acid and saccharin sodium in oral liquid preparations.
• Select
  Exploration of Microbial Limit Test Method for Sirolimus Oral Solutions

  LIU Dongling, JIANG Bo, LIU Hao*

  2017, 48(05): 730. https://doi.org/10.16522/j.cnki.cjph.2017.05.019

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  The microbial limit test method for sirolimus oral solutions from different manufacturers was established, and it was unfied, simple and in accordance with ChP 2015. Several methods were tried in the suitability of microbial limit test. When general method was used in the suitability of the test method, testing samples showed antibiotic effects on Candida albicans in microbial enumeration tests. When the samples were diluted in pH 7.0 sodium chloride buffer-peptone solution (containing 3％ Tween-80, 0.3％ lecithin and 0.1％ histidine) and were made a 1 in 20 dilution, the ratio between the test group and the microorganism solution group were between 0.5 and 2.0. The results indicated that the antimicrobial activity had been eliminated by the combination of diluting method and neutralizing method. It was suitable for the microbial limit test of sirolimus oral solutions.
• Select
  Determination of Related Substances in Enzalutamide Bulk Drug by HPLC

  RUAN Lejun1,2, LI Bonan1,2, LI Jianqi1,2, ZHOU Ainan1,2*

  2017, 48(05): 740. https://doi.org/10.16522/j.cnki.cjph.2017.05.021

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  An HPLC method was established for the determination of the related substances in enzalutamide bulk drug. A Waters SunFireTM C18 column was used, with mobile phase A of aqueous trifluoroacetic acid solution(0.05％) and mobile phase B of acetonitrile by gradient elution, at the detection wavelength of 220 nm. The calibration curves of enzalutamide and its related substances 3—6, 8—12 were linear in the range of 0.3—7.5 μg/ml, while the related substances 2 and 7 were linear in the range of 0.45—11.25 μg/ml. The recoveries for the related substances were 90％—110％, with RSDs of 0.44％—8.38％.
• Select
  Determination of the Related Substances of Pitavastatin Calcium by HPLC

  FU Mengling1, JIANG Jianqin1*, XING Weifan2

  2017, 48(05): 745. https://doi.org/10.16522/j.cnki.cjph.2017.05.022

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  An HPLC method was established for the determination of the related substances in pitavastatin calcium. A C18 column was used, with the mobile phase of acetonitrile∶acetate buffer solution (acetic acid 0.5 ml,ammonium acetate 0.140 6 g, add water to 1 L) by gradient elution, at the detection wavelength of 245 nm. It was linear for pitavastatin calcium and its seven related substances in the range of 0.125—2 μg/ml, while it was linear for its diastereomer in the range of 0.625—10 μg/ml. The maximum single impurities in three batches of samples were 0.021％,0.027％, 0.027％, respectively. The total impurities were 0.108％, 0.054％, 0.110％, respectively.
• Select
  Determination of Related Substances in Tedizolid Phosphate by HPLC

  ZHAN Yufang1, LUO Zhaoliang2, ZHANG Lei3

  2017, 48(05): 749. https://doi.org/10.16522/j.cnki.cjph.2017.05.023

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  An HPLC method was established for the determination of the related substances in tedizolid phosphate. The separation was performed on Zorbax SB-C18 column, and the related substances were determined with 25 mmol/L ammonium bicarbonate solution as the mobile phase A and acetonitrile as the mobile phase B, using a gradient elution (A: 0—40 min, 95％→10％; 40—45 min, 10％; 45—50 min, 10％→95％; 50—55 min, 95％), at the detection wavelength of 300 nm. The 11 known related substances were well separated from tedizolid phosphate under the selected chromatographic condition, with a resolution greater than 1.5, and the resolutions were greater than 2.0 between the related substances. It was linear in the range of 0.1—10 μg/ml for these compounds. The recoveries for the related substances were 93.7％—102.3％, with RSDs of 0.27％—0.77％. The established method is validated to be suitable for the quality control of tedizolid phosphate.
• Select
  Graphical Synthetic Routes of Palbociclib

  ZHOU Haiping1, GAN Zongjie2*

  2017, 48(05): 758. https://doi.org/10.16522/j.cnki.cjph.2017.05.025

  Abstract ( ) Download PDF ( )   Knowledge map   Save
• Select
  Risk Analysis and Strategies for Pharmaceutical Technology Transfer under Drug Reform

  ZHU Hong, LIU Lanru, HAN Yue, ZHANG Ying, LI Zhangming

  2017, 48(05): 762. https://doi.org/10.16522/j.cnki.cjph.2017.05.026

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  Through literature and case research, this paper analyzes the risks on pharmaceutical technology transfer under drug reform, and proposes strategies for the risk prevention. The results show that there are some risks in pharmaceutical technology transfer process, including policy risk, legal risk, market risk and technology risk. Both parties involved should adopt measures, for example, change the mode of pharmaceutical technology transfer appropriately, to
  prevent and control the risks.
• Select
  Visualization Analysis of Chinese Drug Quality Research

  WANG Xinping, LI Zheng, LIU Ping

  2017, 48(05): 774. https://doi.org/10.16522/j.cnki.cjph.2017.05.028

  Abstract ( ) Download PDF ( )   Knowledge map   Save

  In the process of promoting the reform of health care in our country, drug safety problems have occurred occasionally, and the public pays more and more attention to drug quality. This paper takes 3 620 documents collected in CNKI as the research object, using information visualization software, CiteSpaceIII, to make a corresponding scientific knowledge map analysis which is connected with the key words, institutions and authors in drug quality research literatures. The results show that researches on Chinese medicine quality have a tendency to combine with similar research areas, as well as deepening and refining its research content and direction. In recent years, Chinese scholars are constantly applying new technologies, new ideas, and trying to solve the problem of drug safety from much wider areas, while the research in Chinese Medicine is slightly less than above. The pharmaceutical enterprises and hospitals need to strengthen scientific research work, and the clinical practice and scientific research should be further integrated as well. Chinese scholars in drug quality research work lack mutual cooperation between each other. It is, no doubt, of great importance tostrengthen cooperation between them in today's knowledge-sharing world.
• Select
  An Analysis of the Economic Operation of Chinese Pharmaceutical Industry of 2016

  MAO Junfeng1, GUO Wen2, WU Xiaoming3*

  2017, 48(05): 781. https://doi.org/10.16522/j.cnki.cjph.2017.05.029

  Abstract ( ) Download PDF ( )   Knowledge map   Save