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
Chinese Journal of Pharmaceuticals

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    Perspective & Review
  • Perspective & Review
    Recent Advances in the Application of Co-amorphous Drug Delivery Systems in Pharmaceutical Fields
    CHEN Jiaxin, LI Shuo, ZHANG Huangliang, WANG Jue, LIU Xiaoqian, HAN Jiawei
    2026, 57(4): 377. https://doi.org/10.16522/j.cnki.cjph.2026.04.001
    Abstract ( )   Knowledge map   Save
    Co-amorphous drug delivery systems are homogeneous single-phase systems composed of two compatible drugs or a drug combined with a small-molecule ligand exhibiting high biosafety. As a highly promising formulation technology, these systems have been widely used to improve the critical in vitro and in vivo properties of poorly soluble drugs, including solubility, dissolution, physical stability, and bioavailability. This paper systematically reviews the latest research advances in this field, focusing on the classification, preparation techniques, physicochemical properties, and in vivo biological performance of drug co-amorphous systems, aiming to provide a reference for the development and application of co-amorphous drug delivery systems.
  • Perspective & Review
    Research Progress in Pharmaceutics of Nasal Environmentally Responsive in Situ Gels
    PENG Zhirong, TAN Jiaozhang, ZHOU Yilin, LIU Yang
    2026, 57(4): 386. https://doi.org/10.16522/j.cnki.cjph.2026.04.002
    Abstract ( )   Knowledge map   Save
    Nasal drug delivery has garnered considerable attention in the treatment of local and systemic diseases due to its non-invasive nature, ability to bypass the hepatic first-pass effect, and rapid drug absorption. However, traditional nasal preparations suffer from limitations such as rapid clearance, short retention time, low bioavailability, and poor patient compliance. Environmentally responsive in situ gels, as a new type of drug delivery system, can sense specific physiological or physicochemical signals in the nasal cavity and trigger a solution-to-gel phase transition. This characteristic endows them with the dual advantages of dosing accuracy and ease of administration of liquid formulations, along with the prolonged nasal retention of semi-solid formulations, providing a new approach to overcome the limitations of traditional nasal preparations. Nevertheless, several challenges remain in practical applications, including unstable industrial production processes and insufficient long-term stability. This article systematically reviews the characteristics, classification, preparation process, and quality evaluation systems of nasal environmentally responsive in situ gels, aiming to provide a reference for their further development and application in nasal drug delivery.
  • Perspective & Review
    Biological Function and Application Prospects of Probiotic Exosomes
    GAO Ruyuan, HU Haifeng
    2026, 57(4): 393. https://doi.org/10.16522/j.cnki.cjph.2026.04.003
    Abstract ( )   Knowledge map   Save
    Probiotic exosomes are nanoscale vesicles secreted by probiotics, which are capable of carrying various bioactive molecules such as proteins, nucleic acids and lipids. In addition to regulating host immunity, maintaining intestinal microecological balance, and exerting antimicrobial effects, they possess multiple biological functions including intestinal barrier protection, metabolic regulation, and neuroregulation. This review summarizes recent research progress of probiotic exosomes, systematically outlines the specific functions and potential action mechanisms of exosomes derived from different probiotic sources, and deeply explores their application prospects and industrial advantages in disease therapy, drug delivery and vaccine development. On this basis, this review points out current technical and translational bottlenecks in this field, aiming to provide new insights and directions for the subsequent basic research and industrial applications related to probiotic exosomes.
    • Paper
  • Paper
    The Novel Synthetic Route of Bezisterim
    GAO Yuchen, LIU Yazi, HU Ninglin, CONG Yuwen,
    2026, 57(4): 399. https://doi.org/10.16522/j.cnki.cjph.2026.04.004
    Abstract ( )   Knowledge map   Save
    Herein the synthesis of bezisterim(HE 3286, 1) was improved and optimized. Using [(3S,8R,9S,10R,13S,14S)- 10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl]acetate(2) as the starting material, an alkynylation reaction was performed to yield (3S,10R,13S,17R)-17-ethynyl-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16- dodecahydrocyclopenta[a]phenanthrene-3,17-diol(3). Compound 3 was then subjected to diesterification to produce (3S,10R, 13S,17R)-17-ethynyl-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-diacetate(4). Subsequently, compound 4 underwent the oxidation to yield (3S,10R,13S,17R)-3,17-diacetoxy-17-ethynyl-10,13-dimethyl- 1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-7-one(5). Compound 5 was then reduced to obtain (3S,10R,13S,17R)-3,17-diacetoxy-17-ethynyl-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]- phenanthren-7-ol(6). Finally, compound 6 underwent alcoholysis and deprotection to yield compound 1, achieving an overall yield of 28.3％ (based on 2) and the purity of 98.93％ . This reaction route features mild process conditions, straightforward operation, and controllable quality, making it suitable for industrial production.
  • Paper
    Optimization of the Synthesis Process of Aminolevulinic Acid Hydrochloride
    CHANG Jinke, LIU Yi, ZHANG Naihua, ZHU Shiguo,
    2026, 57(4): 407. https://doi.org/10.16522/j.cnki.cjph.2026.04.005
    Abstract ( )   Knowledge map   Save
    A synthetic process of aminolevulinic acid hydrochloride(1) was optimized. Starting with phthalimide(2), a nucleophilic substitution reaction with epichlorohydrin yielded a mixture of N-(2,3-epoxypropyl)- phthalimide(3) and 2-(3-chloro-2-hydroxypropyl)-1H-isoindoline-1,3(2H)-dione(6). Subsequently, compound 3 was converted to 6 via HCl-mediated epoxide ring-opening. Next, 6 was oxidized using Jones reagent to afford 2-(3-chloro- 2-oxopropyl)-1H-isoindoline-1,3(2H)-dione(4). Using triethylamine as an acid scavenger, 4 underwent a substitution reaction with Meldrum’s acid to synthesize 2-[3-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-yl)-2-oxopropyl]-1H-isoindoline- 1,3-dione(5). Finally, 5 was hydrolyzed with HCl to yield the target product 1. After purification, the optimized process achieved a total yield of 66.8％ (based on 2) with 99.6％ purity. During the reaction of 2 with epichlorohydrin, potassium carbonate was not required, thus avoiding the formation of impurities A, B, and C. In the synthesis of 4, the “onepot method” of the original process was optimized to a two-step synthesis, thereby eliminating the risk of chlorine gas generation. For the post-treatment of 4, trituration with isopropanol was employed, obviating the cumbersome column chromatography operation. The hydrolysis time of 5 was optimized to eliminate the residual hydrolysis intermediate. By improving the purification method, the formation of dimer impurity in the final product was avoided. The simplified operation, reduced production cost, and excellent reproducibility have been successfully demonstrated at kilogram-scale, confirming its suitability for industrial production.
  • Paper
    Improved Synthesis of Pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one
    SUN Mao, LIU Xianji, LIU Yuanyuan, WANG Chuanling, YAN Chen
    2026, 57(4): 413. https://doi.org/10.16522/j.cnki.cjph.2026.04.006
    Abstract ( )   Knowledge map   Save
    The synthetic process of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-one(1) was optimized via a fourstep reaction sequence. Starting from 2,5-dimethoxytetrahydrofuran(6) and tert-butoxycarbonyl hydrazine, tert-butyl (1H-pyrrol-1-yl)carbamate(7) was obtained via a Clauson-Kaas pyrrole synthesis. Subsequent formamidation of compound 7 with chlorosulfonyl isocyanate afforded the key intermediate tert-butyl (2-carbamoyl-1H-pyrrol-1-yl)carbamate(9). Deprotection of 9 with hydrogen chloride followed by cyclization with trimethyl orthoformate yielded the target 1 with an overall yield of 60.7％ (based on tert-butoxycarbonyl hydrazine) and a purity of 99.51％ . This process achieves the “onepot method” synthesis of key intermediate 9 from compound 7. All intermediates were purified via simple crystallization or slurrying, resulting in a straightforward, robust, and industrially viable protocol.
  • Paper
    Josamycin Biosynthetic Gene Cluster and Genetic Engineering Modification of Streptomyces narbonensis
    ZHANG Wanying, ZHANG Haixia, ZHANG Zhengyu, YANG Songbai, TAN Jun, CHEN Shaoxin
    2026, 57(4): 419. https://doi.org/10.16522/j.cnki.cjph.2026.04.007
    Abstract ( )   Knowledge map   Save
    Josamycin(1) is a macrolide antibiotic primarily produced by Streptomyces narbonensis var. Josamyceticus(S. narbonensis) through fermentation. It is widely used to treat respiratory and urinary tract infections. Currently, the domestic supply of the active pharmaceutical ingredient of 1 relies on imports, making it of great significance to explore microbial fermentation for its industrial production. This study performed whole genome sequencing on S. narbonensis J-2-40, conducted functional annotation of its encoded proteins, analyzed and annotated its biosynthetic gene clusters, and speculated the biosynthetic pathway of 1. The results showed that the total length of the 1 biosynthetic gene cluster sequence is 73 893 bp, containing 38 open reading frames. It exhibited the characteristics of modular type Ⅰ polyketide synthase architecture. The biosynthetic pathway of 1 mainly included polyketide precursor synthesis, polyketide chain elongation, glycosyl side chain assembly, and post-assembly modifications. Based on this, genetic engineering modifications on the 1 producing strain S. narbonensis were investigated by overexpressing acyltransferase genes (orf 9, orf 29) and acetyl-CoA carboxylase gene (accA2BE). Finally, the engineered strains, JOS-ORF29 and JOS-A2BE were successfully constructed, achieving 13％ and 31％ increases in yield compared to the parental strain, respectively.
  • Paper
    Investigation of the Improvement Effect of PVP on the Solubility and Stability of Baicalin-imperatorin Co-amorphous System
    JIANG Qieying, SU Tong, CHEN Tingchao, TONG Yu, LAI Anqi, LIAO Zhenggen
    2026, 57(4): 427. https://doi.org/10.16522/j.cnki.cjph.2026.04.008
    Abstract ( )   Knowledge map   Save
    In this study, baicalin(1)-imperatorin(2) co-amorphous systems(CAS), both with and without PVP, were prepared by spray drying. The solid-state characteristics of the obtained CAS were characterized by powder X-ray diffraction(PXRD) and differential scanning calorimetry(DSC). The results showed that adding a small amount of PVP did not change the equilibrium solubility of 1 and 2, but increased the glass transition temperature(Tg) of the CAS from 64.0 ℃ to 77.0 ℃ . Compared with 1-2-CAS, the 1-2-PVP-CAS showed significantly enhanced 6-h dissolution AUC0→6 h values of mass concentration-time curves for 1 and 2 by 30.4％ and 23.6％ , respectively. The dispersion time was shortened by 48％ relative to 1-2-CAS, while the agglomeration rate was decreased from 55.82％ to 44.28％ , and the surface free energy increased to 32.27 mN/m. Crystallization behavior studies revealed that PVP significantly inhibited the crystal nucleation and growth of 1, but had no significant effect on 2. Accelerated stability testing(40 ℃ /75 ％ RH) showed that 1-2-PVP-CAS remained amorphous after 14 d of storage, whereas the 1-2-CAS without PVP exhibited obvious crystallization. In addition, the addition of PVP did not affect the water content of the CAS. These findings indicate that, without compromising the solubility of poorly soluble drugs, the addition of a small amount of PVP improved the dissolution properties of 1 and 2 in 1-2-CAS by improving wettability and dispersion as well as inhibiting crystallization, while simultaneously improving storage stability through increasing the Tg of the CAS. This study provides a theoretical and methodological reference for the rational design of co-amorphous systems of poorly soluble drug combinations.
  • Paper
    Evaluation and Application of Torque Endpoint Control in High Shear Wet Granulation of Sertraline Hydrochloride Tablets
    HU Xiubo, LIU Rui
    2026, 57(4): 436. https://doi.org/10.16522/j.cnki.cjph.2026.04.009
    Abstract ( )   Knowledge map   Save
    This study investigated the relationship between torque, granule size, and drug dissolution during highshear wet granulation, evaluating the feasibility of using torque as an endpoint indicator for the high-shear wet granulation of sertraline hydrochloride tablets. A fractional factorial experimental design was employed, consisting of a four-factor, twolevel test involving water addition, impeller speed, chopper speed, and granulation time. The plateau torque was used as a covariate, and the particle size [d(0.6)], compressibility, and tablet dissolution curve in pH 6.8 PBS were used as responses to identify the factors that played a decisive role in granule preparation. The results demonstrated that torque-based endpoint determination effectively controlled the granulation endpoint and enabled predictability of particle size and tablet dissolution curve. In conclusion, it is feasible to use torque as the endpoint indicator for the high-shear wet granulation of sertraline hydrochloride tablets, and it can serve as a key parameter for guiding production scale-up.
  • Paper
    Establishment of the Dissolution Detection Method for Nalfurafine Hydrochloride Orodispersible Films
    CONG Rong, WANG Jun, WEN Hongliang, LE Jian, LIU Hao
    2026, 57(4): 443. https://doi.org/10.16522/j.cnki.cjph.2026.04.010
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    Accurate evaluation of drug dissolution is of great significance for the quality control of orally dissolving film(ODF). The traditional paddle-disk method differs significantly from the actual physiological conditions in the oral cavity and suffers from insufficient discriminatory ability. In this study, nalfurafine hydrochloride ODF was selected as the model, and a dissolution testing method was established using the closed-loop flow-through cell method, with optimization of conditions such as dissolution medium, flow rate, and amount of glass beads. Additionally, an ODF fixing device suitable for a 22.6 mm cell body was designed to prevent ODF samples from floating and adhering during the test. The results showed that after three batches of nalfurafine hydrochloride ODF were fixed using the designed device, they all exhibited stable dissolution behavior with low intra- and inter-batch variability under the conditions of artificial saliva as the dissolution medium, a flow rate of 4 mL/min, and 6.5 g of filled glass beads. Compared with the traditional paddledisk method, the test involves no mechanical stirring, which is more in line with the actual drug-release environment of oral films and has better discriminatory power.
  • Paper
    Quality Control of Turmeric Extract Based on Characteristic Fingerprint and Quantitative Analysis of Multi-components by Single Marker
    WU Yugang#, FENG Yukang#, LI Jianwen, WANG Jiali, WU Tong, LIN Shan
    2026, 57(4): 451. https://doi.org/10.16522/j.cnki.cjph.2026.04.011
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    A characteristic fingerprint method and a quantitative analysis of multi-components by single marker(QAMS) method were established based on a UPLC method. Using curcumin(1) as the reference substance, the characteristic fingerprint and the content of four components in turmeric extract, namely 1, bisdemethoxycurcumin(2), demethoxycurcumin(3) and dihydrocurcumin(4), were simultaneously determined. The results showed that 7 characteristic peaks in characteristic fingerprint were 1 - 4 and the enol isomers of 1, 3, 4. No significant difference was observed between the QAMS and the external standard method, the total content of compounds 1 - 4 in turmeric extract was 72.81％ . Moreover, the content of phenols in turmeric extract was measured to be about 85％ using UV method. In this study, the quality control of turmeric extract was carried out based on characteristic fingerprint and QAMS, which provided methodological support and essential data for the improvement of its quality standards.
  • Paper
    Comparative Study on Detection Methods of Anti-drug Antibody for PEGylated Human Granulocyte Colony-stimulating Factor
    XU Tingting, WANG Danyang, JIANG Yu, ZHOU Li, QIU Yunliang
    2026, 57(4): 458. https://doi.org/10.16522/j.cnki.cjph.2026.04.012
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    In this study, electrochemiluminescence immunoassay(ECLIA) and surface plasmon resonance(SPR) were employed, in combination with three distinct sample pretreatment approaches(dilution, acid dissociation, and magnetic bead purification), to respectively detect anti-drug antibodies(ADA) against PEGylated human granulocyte colonystimulating factor(PEG-G-CSF) in cynomolgus monkey serum samples. The sensitivity, drug tolerance, method selectivity, and other key performance parameters of each detection method and sample pretreatment strategy were systematically compared. The results demonstrated that for the samples after dilution pretreatment, the method sensitivity of ECLIA was 24 ng/mL, and the assay could tolerate 4 000 ng/mL of the drug at a positive control antibody concentration of 500 ng/mL. In contrast, the method sensitivity of SPR was 441 ng/mL, but the assay failed to tolerate 125 ng/mL of the drug at the same positive control antibody concentration. Compared with the dilution approach, acid dissociation failed to enhance the method sensitivity and drug tolerance of either detection method. Moreover, after magnetic bead purification of the test samples, the signal values significantly declined, resulting in the poorer method sensitivity. This study indicated that the combination of ECLIA with dilution pretreatment showed excellent precision and selectivity, lacked the hook effect, and was applicable to the evaluation of ADA levels against PEG-G-CSF.
  • Paper
    Analysis of Microbial Contamination Characteristics and Source Tracking in Cleanrooms of Medical Devices Based on 16S rRNA Sequencing and Protein Fingerprinting
    ZHANG Yun, DING Qi, MENG Yang, HE Shiyao, WU Wenting, KANG Yan
    2026, 57(4): 467. https://doi.org/10.16522/j.cnki.cjph.2026.04.013
    Abstract ( )   Knowledge map   Save
    To assess microbial contamination characteristics in cleanroom environments of medical device manufacturing and explore effective monitoring strategies, this study selected three 100 000-garde clean rooms from two enterprises in Jiangxi province. The airborne bacteria were sampled and analyzed using full-length 16S rRNA gene sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for microbial protein fingerprinting. A total of 42 strains of microorganisms were isolated and identified. The results showed that the dominant genera were Staphylococcus(21.4％ ), Moraxella(14.2％ ), and Micrococcus(11.9％ ), and three strains of fungi were detected. The microbial community composition differed significantly among different factory areas, and most strains were region-specific, reflecting the dependence of microbial contamination on environmental conditions. Among them, Moraxella osloensis(M. osloensis) was the only dominant strain found in all three factory areas. It might be carried by personnel, suggesting that the enterprises should enhance personnel hygiene and disinfection management. Further protein fingerprinting analysis of six M. osloensis strains revealed that although the overall spectra were highly consistent, strain-specific protein peaks were still present, indicating that this technique has certain limitations in strain discrimination. The combination of molecular biology and proteomics technologies can improve the accuracy of environmental microbial monitoring. It is recommended that relevant enterprises should establish a multi-point regular monitoring system, optimize disinfection strategies, and promote the construction of a localized protein fingerprint database to enhance the overall ability to c ontrol microbial contamination.
    • Pharmaceutical Management & Information
  • Pharmaceutical Management & Information
    Challenges and Improvement Paths of the Consistency Evaluation System for Generic Drugs Selected in China’s Centralized Procurement
    LI Xinyi, MA Shaoqing
    2026, 57(4): 467. https://doi.org/10.16522/j.cnki.cjph.2026.04.014
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  • Pharmaceutical Management & Information
    Research on the Layout Strategy of SHP2 Inhibitors Based on Patent Data
    YANG Chao,
    2026, 57(4): 481. https://doi.org/10.16522/j.cnki.cjph.2026.04.015
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  • Pharmaceutical Management & Information
    Analysis of Factors Affecting the Quality of Purified Water Produced by Reverse Osmosis Process
    WU Yu, CHEN Fuchao, CAO Minjing, ZHENG Haixia, YANG Lei
    2026, 57(4): 487. https://doi.org/10.16522/j.cnki.cjph.2026.04.016
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  • Pharmaceutical Management & Information
    Feasibility Study on Rare Disease Sector as a Strategic Pivot for Innovative Drug Development in China from the Perspective of Industrial Management
    LIU Jianhui, MAO Yufeng
    2026, 57(4): 494. https://doi.org/10.16522/j.cnki.cjph.2026.04.017
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