主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA

Archive

  • Select all
    |
    Perspectives & Review
  • Perspectives & Review
    HOU Zhiyuan, ZHANG Hailong, DING Jinsong
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Vitamin D3(VD3) is an essential drug for treatment of metabolic bone diseases, such as rickets, osteomalacia and osteoporosis. The supplement of exogenous low-dose VD3 can alleviate the disease progression effectively. However, the chemical property of VD3 is particularly unstable, and VD3 usually used as a low-dose active ingredient of compound preparations with other high-dose active ingredients such as calcium compounds. So we face dual challenges to improve the stability and content uniformity of VD3 in the preparations. This paper reviews past efforts in the research and development of improving the stability and content uniformity of VD3 compound solid preparations, analyzes the key factors affecting the quality of the VD3 preparations during the pharmaceutical manufacturing processes, and proposes corresponding solutions. It is expected to provide some references for the research & development and quality standard improvement of VD3 compound solid preparations.
  • Perspectives & Review
    LI Ruipeng, ZHAO Jianhong, XIA Guangxin, XIE Jianshu, DENG Weiping
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Mitogen-activated extracellular signal-regulated kinase(MEK) inhibitors are important antineoplastics. At present, four drugs have been marketed, namely trametinib, cobimetinib, selumetinib and binimetinib. This paper briefly introduces these drugs and reviews their reported synthetic routes.
  • Perspectives & Review
    HUANG Lu, GU Shuangxi, HONG Yi
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The approved and investigational varieties of highly selective rearranged during transfection(RET) tyrosine kinase inhibitors have been summarized in this paper. The research and development progress, as well as the published technical patents of the three key drugs, namely selpercatinib, pralsetinib and BOS-589, are analyzed. It provides effective patent information and references for pharmaceutical enterprises in the process of establishing and developing projects of RET tyrosine kinase inhibitors for innovative or generic drugs, as well as new patent mining, patent protection and layout.
  • Perspectives & Review
    ZHANG Yan, ZHU Liang, LIU Tuankun, MA Yajuan
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The polymorphism regulation and computational simulation in the research of pharmaceutical polymorphs have gradually become one of the research hotspots in the pharmaceutical field. Stable superior crystalline forms for industrial production can be obtained through polymorphism regulation. As a research method, computational simulation greatly reduces the experimental cost and helps researchers understand the reasons for the formation of drug polymorphs at the molecular level. In this paper, the effect of polymorphism on the physicochemical properties of drugs is described firstly. Then, the pharmaceutical polymorph control methods are sorted out, especially focusing on the ionic liquid- and additive-induced polymorphisms. In addition, the application of computational simulation in the research of pharmaceutical polymorphism is introduced. We hope to provide some references for the selection of suitable crystalline forms for clinic use and drug discovery.
  • Perspectives & Review
    ZHANG Tao, ZHANG Meng, HAO Jianping, GAO Yanping, LI Jianwei
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    This paper is a summarization for marketing history of the paracetamol-containing reference listed drug(RLD), the changes in pharmaceutical regulations related to quality and efficacy consistency evaluation, pharmacokinetic parameters and in vitro-in vivo correlation research data of generic paracetamol tablets. And this paper briefly summarizes the literature basis for generic paracetamol tablets exempted from bioequivalence studies according to the National Medical Products Administration guidance, and the regulatory approval of the generic tablets only requires the consistency of pharmaceutical equivalence studies to the RLD.
  • Perspectives & Review
    ZHANG Jing, ZHAI Xiaoyu, ZHANG Beibei, ZHANG Qing, ZHANG Yilan
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The sources, hazards and current detection methods of nitrosamines in medical packaging elastomers are described in this paper. In order to provide some references for related researchers, the research situation of nitrosamines in medical packaging elastomers at home and abroad is summarized by consulting the literature.
  • Paper
  • Paper
    BAO Guanglong, ZHANG Naihua, CHEN Chengfu, ZHANG Zongyuan, ZHANG Guimin
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An improved synthetic process of aceclofenac(1) was developed. Commercially available diclofenac sodium(2) was subjected to a nucleophilic substitution with tert-butyl 2-chloroacetate(3), following by refining with methanol, to provide the key intermediate tert-butyl aceclofenac(4). Subsequently, the target compound 1 was obtained through hydrolysis reaction of 4 on exposure to HCl-AcOH condition, following by recrystallization in AcOH with an overall yield of 75.4%(based on 2) and a purity of over 99.9%. The optimized process bearing mild reaction conditions, simple operation and stable process has been tested by process verification, and it is suitable for industrial production.
  • Paper
    MOU Hong, QI Yangli, GONG Yanqing, CHEN Xiaowen, LI Jianqi
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    2-Amino-5-(2-fluorophenyl)furan-3-carbonitrile is a key process impurity in the synthesis of vonoprazan fumarate as a potassium competitive acid blocker. Its structure contains basic groups, but it is not easy to be removed by acid washing. In this study, a single crystal of 2-amino-5-(2-fluorophenyl)furan-3-carbonitrile was cultivated by solvent evaporation method, and characterized by X-ray single crystal diffraction. The results showed that hydrogen bonds were presented in the crystalline state, two adjacent molecules formed quasi-dimer via a pair of hydrogen bonds between them, and the stable arrangement in space was maintained by van der Waals forces and hydrogen bonds. Therefore, the ionization ability of N atoms of amino group in the structure was reduced, and the alkalinity was decreased, which explained the possible reason why it was difficult for the impurity to be removed by simple washing with the acidic solution.
  • Paper
    XIE Yaru, Wang Guanru, Sun Kaoxiang
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Using hydrogenated soybean phosphotidylcholine, distearoylphosphatidylethanolamine-polyethylene glycol 2000 and cholesterol as carriers, long-circulating liposomes of docetaxel(lip-DTX) were prepared by thin-film dispersion. On this basis, mouse 4T1 breast cancer cell membrane-encapsulated docetaxel long-circulating liposomes(4T1/ lip-DTX) were prepared by co-extrusion. The morphologies of lip-DTX and 4T1/lip-DTX pictured by TEM were round. The particle size and zeta potential for lip-DTX and 4T1/lip-DTX measured by the analyzer were (149.6±0.1) and (126.7± 0.6)nm, (–40.5±2.1) and (–6.3±1.2)mV, respectively. The encapsulation efficiencies measured by ultrafiltration were (72.4±0.3)% and (74.1±0.2)% for lip-DTX and 4T1/lip-DTX, while the drug loading were (3.0±0.1)% and (2.5±0.5)%. No significant changes were observed in particle size and encapsulation efficiency of lip-DTX and 4T1/lip-DTX stored at 4 ℃ for 4 days. The results of in vitro release test showed that the cumulative amount at 12 h of lip-DTX was (69.5±0.4)%. While the cumulative amount at 8 h of 4T1/lip-DTX was (22.2±0.3)%, showing a slower release rate compared to lip- DTX. The cell uptake test showed that the uptake of lip-DTX by mouse monocyte macrophage cell line RAW 264.7 was 1.4 times that of 4T1/lip-DTX (P<0.01), and the uptake of 4T1/lip-DTX by 4T1 cells was 1.5 times that of lip-DTX (P<0.001), indicating the long circulation and targeting properties of 4T1/lip-DTX. The in vitro cytotoxicity test showed that the IC50 values of lip-DTX and 4T1/lip-DTX against 4T1 cells were 7.6 and 1.5 μg/ml, which indicated that 4T1/lip- DTX could increase the antitumor efficacy of docetaxel.
  • Paper
    FENG Zhong, WEI Ruixia, JIA Junwei, CHEN Mengyu, YAN Jiyong, ZHANG Guimin
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Enteric-coated pellets of esomeprazole magnesium were prepared by bottom spray fluid bed process. First, the blank sugar pellets were coated with a 15%-solid-content liquid containing 2% hydroxypropyl methylcellulose E5 LV, 0.3% talc and the bulk drug. Then, the drug-coated pellets were coated with a 10%-solid-content liquid containing the mixture of hydroxypropyl cellulose LF and talc(1∶2), and the weight gain of this isolation layer was (23±2)%. After that, the above pellets were coated with a 15%-solid-content liquid containing Eudragit L30D-55, triethyl citrate and Tween-80 (28∶4∶5). The final enteric pellets were obtained when the weight gain of enteric layer reached 45% - 50%. Finally, the title tablets were obtained by blending with microcrystalline cellulose(with ratio of MCC 101 to MCC 102 of 40∶60), crospovidone and sodium stearyl fumarate, compression and coating with a film layer. The results showed that the content uniformity, acid resistance and release of the coated tablets met the requirements of Chinese pharmacopoeia 2020. A method for determination of esomeprazole in Beagle dog plasma by LC-MS was established. Under fasting condition, cmax of the self-made pellet-based tablets and reference preparation were (287.16±13.37) and (290.34±12.42)ng/ml, tmax were (1.34±1.37) and (1.41±2.37)h, respectively. The oral relative bioavailability of the selfmade preparation was (98.5±6.7)%. Under feeding condition, AUC and cmax obviously decreased for both self-made and reference preparations. This process could solve the acid instability problem of esomeprazole magnesium.
  • Paper
    SHUI Linsen, LI Yang, LIU Luan, LIU Jianqiao, GUO Yongxue
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    There are many process parameters that affect the granule characteristics in the top-spray fluidized bed granulation. The blank microcrystalline cellulose granules with hypromellose as a binder were prepared by fluidized bed granulation in this paper to investigate the influences of various process parameters. According to the results of single factor experiments, a customized design in JMP version 13.2.0 software was adopted to investigate the influences of concentration and flow rate of the binder, spray pressure and nozzle height(as a discrete variable) on the compressibility, average particle size, size distribution(span) and flowability of the targeted granules. And the regression models and interaction diagrams were established to evaluate the interaction between above parameters. The results showed that when the nozzle height was set at a high level, the higher flow rate of the binder, the smaller degree of compressibility of the targeted granules; however, when the nozzle height was set at a low level, the degree of compressibility was rather stable. When the spray pressure was set at a low level, increasing the binder concentration was beneficial to increase the average particle size of the granules. But the change of particle size with the binder concentration was not obvious at the high level of the spray pressure. The particle size decreased with the increasing of the spray pressure. At a low level of spray pressure, the flowability increased significantly with the increasing of the binder flow rate, but the flowability decreased slightly at a high level of spray pressure.
  • Paper
    CHENG Yujie, HOU Hao, WANG Yi, YANG Bo, HU Zheng
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The performance of self-developed immunochromatographic colloidal gold test strips for detecting Moraxella catarrhalis was tested. Test strips were selected randomly and cross-reacted with common respiratory pathogens to detect their sensitivity. In addition, the interference effects of internal and external interferences, hook effect of the test strips and storage stability of the test strips between batches were also tested. The results showed that the immunochromatographic colloidal gold test strips for detecting Moraxella catarrhalis had a detection sensitivity of 3.25×104 CFU/ml. The test strips had no cross-reactivity to other 22 common respiratory pathogens and could keep stable for more than one and a half years. No hook effect was observed when the bacterial concentration was 1.0×107 - 1.0× 109 CFU/ml, and neither endogenous nor exogenous interfering substances could interfere with the detection results. The accuracy, sensitivity and stability of the test strips met the requirements of mass production, as well as the registration requirements of in vitro diagnostic reagent products.
  • Paper
    MOU Jianping, TENG Baoxia, HE Xiaowen, ZHU Ling, ZENG Xiaomei
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An HPLC method was established to determine the bacteriostatic agent(ethyl p-hydroxybenzoate) in sodium cromoglycate eye drops. Seven batches of commercially available sodium cromoglycate eye drops from different companies were examined on the content and bacteriostatic efficacy of the bacteriostatic agent according to the bacteriostatic efficacy inspection method of the general rules 1121 in the 2020 edition of the Pharmacopoeia of the People's Republic of China(ChP 2020). Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus niger were used as test microorganisms, and the logarithms of the number of viable microorganisms were determined at different times points. The results showed that the contents of ethyl p-hydroxybenzoate for the tested samples were in the range of 0.18–0.45 mg/ml, and at 6 h, 24 h, 7 d, and 14 d after adding different test microorganisms, the logarithmic reduction values of the seven tested samples did not meet the corresponding requirements of the ophthalmic preparations in ChP 2020. It suggested that the companies should screen out an effective bacteriostatic agent in prescriptions to ensure drug safety.
  • Paper
    SUN Baodan, ZHOU Lingqi, LIU Hongqiao
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An HPLC method was established to determine the enantiomeric impurities in N-Cbz-Lhistidine( Cbz-L-His-OH) and 1-[(1,1-dimethylethoxy)carbonyl]-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-Lhistidine[ Fmoc-L-His(Boc)-OH]. An DAICEL CHIRALPAK? ZWIX(+) column was used, with the mobile phase of methanol∶water∶formic acid∶diethylamine (900∶100∶1.9∶4.16). The column temperature was 35 ℃, the flow rate was 0.2 ml/min, the injection volume was 10 μl, and the detection wavelength was 220 nm. The results showed that the L- and D-enantiomers of Cbz-His-OH as well as Fmoc-His(Boc)-OH could be separated effectively. The detection and quantification limits of Cbz-D-His-OH were 141 and 476 ng/ml, for Fmoc-D-His(Boc)-OH were were 50 and 163 ng/ml, respectively. It was linear for the two pairs of enantiomers in the corresponding concentration ranges. The recoveries of both Cbz-D-His-OH and Fmoc-D-His(Boc)-OH were between 90.0% and 100.0%, and the RSDs(n=9) were less than 3.0%. The measurement results showed that contents of enantiomeric impurities in Cbz-L-His-OH and Fmoc-LHis( Boc)-OH were both less than 0.01%. The established method had strong specificity, good reproducibility and high accuracy, which provided a reference for the determination of enantiomeric impurities in Cbz-L-His-OH and Fmoc-LHis( Boc)-OH.
  • Paper
    ZHENG Ye, ZHANG Fangfang, ZHANG Fenglan, LIU Yuan, XIE Shuting
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    A GC method was established for the determination of five siloxanes, namely hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane and tetradecamethylcycloheptasiloxane, in three kinds of silicone products[silicone tube, sealing gasket(small) and sealing gasket(large)] in three different extraction solutions(pH 2.5 buffer, pH 12 buffer and 50% ethanol). Column HP-5 (320 μm×30 m×0.25 μm) was used, and 2,6-di-tert-butyl-4-ethylphenol was used as the internal standard. The results showed that all the five siloxanes were linear in the range of 2–100 μg/ml. The average recovery rates(n=3) in pH 2.5 buffer, pH 12 buffer, and 50% ethanol were 82.1%–100.0%, 80.8%–100.3% and 81.9%–100.4% respectively, with RSDs of 0–0.8%, 0–1.7%, 0–0.7% respectively. This paper provided a reference for the determination of siloxanes in silicone products for pharmaceutical use.
  • Paper
    LI Yue, SUN Huimin
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An HPLC method was established for simultaneous determination of vulcanizing agent p-tertoctylphenol( PTOP) and antioxidant 2,6-di-t-butyl-4-methylphenol(BHT) in halogenated butyl rubber stoppers and their extractables and leachables. An Agilent SB-C18 column was used with the mobile phase comprising of different ratios of acetonitrile to water in gradient elution mode. The detection wavelength was set at 278 nm. Both PTOP and BHT had good linearities in the range of 5 - 50 μg/ml. In extraction and migration experiments, the recovery rates of two substances were in the range of 80% - 120%. Both PTOP and BHT were extracted from the halogenated butyl rubber stoppers, and they had not been detected in the medicines stored under the accelerate condition for 0, 3 and 6 months or under longterm stability storage condition for 10 months. However, PTOP was detected in the medicines stored under the accelerate condition for for 24 months. This method is accurate and suitable for determination of PTOP and BHT in halogenated butyl rubber stoppers for pharmaceutical use and evaluation of the migration situation in medicines.
  • Pharmaceutical Management & Information
  • Pharmaceutical Management & Information
    GENG Ying, ZHANG Hao, JIANG Yonglin, WANG Liqing, YANG Zhimin
    Abstract ( ) Download PDF ( )   Knowledge map   Save
  • Pharmaceutical Management & Information
    ZHANG Lanping, WANG Yin, CHEN Junchen
    Abstract ( ) Download PDF ( )   Knowledge map   Save
  • Pharmaceutical Management & Information
    LI Yue, XIONG Haoshu, JU Wei, LI Weixia, LIN Jianping, ZHAO Yunxia, ZHANG Shunnan, YAN Kaijing
    Abstract ( ) Download PDF ( )   Knowledge map   Save