OBJECTIVE To explore the feasibility of using cyclic olefin polymer (COP) as packaging material for human albumin products. METHODS Human albumin products were stored in COP bottles. Under the conditions of long-term stability (2-8 ℃ for 24 months) and accelerated stability [(25±2) ℃ for 12 months], the key quality indexes of albumin and the probable extracts of COP material were analyzed, and the seal integrity of COP packages was tested. RESULTS Under both test conditions, the appearance, visible foreign matter, numbers of insoluble particles, pH, purity, polymer content, residual aluminum content, protein content, activity of prekallikrein activator and abnormal toxicity of the albumin products all conformed to the quality standards and met the requirements of Chinese Pharmacopoeia. In the products, the contents of molybdenum, nickel, methylbenzene, and cyclohexane that may be produced by COP bottles were all lower than the quality standard limits. Moreover, the human albumin packaging container assembled by COP bottle, halogenated butyl rubber plug and aluminum-plastic combination cap showed excellent package integrity. CONCLUSION COP can be used in the storage and transport of human albumin.

OBJECTIVE To investigate the penetration effect of solid microneedle in vivo and in vitro, the model drug ketoprofen was administered in the form of a patch. METHODS Using a rat skin penetration test, the effects of microneedle length, pre-treatment pressure, pre-treatment time, and types of needle on the penetration enhancement of ketoprofen in vitro were investigated. The pharmacokinetic characteristics of ketoprofen patches applied to the back of rats after different microneedle treatments were investigated, as well as the effect of the ketoprofen patch on promoting permeability in vivo. RESULTS In vitro, skin permeation tests revealed that after microneedle pretreatment, the permeation rate and permeation volume of the patch were significantly increased (P<0.05) and the permeation time lag was significantly shortened (P<0.05) after microneedle pretreatment, while the permeation promotion effect was related to the pressure, time, microneedle length and type of microneedle pretreatment. After microneedle pretreatment of the skin (pressure: 1-7 N, time: 1-5 min, microneedle length: 200 μm-300 μm), the cumulative permeation amount of the experimental drug for 24 hours increased by 1.16-3.09 times, and the permeation delay decreases by 0.20-2.50 h. As the results of in vivo pharmacokinetic in rats, ρ_max (10.86±0.80) μg·mL^-1 and AUC_0→t (108.10±17.06) μg·h·mL^-1 after 300 μm roller microneedle pretreatment of the skin, which were significantly greater than the control ρ_max (0.42±0.03) μg·mL^-1 and AUC_0→t (7.46±0.98) μg·h·mL^-1(P<0.05). ρ_max and AUC_0→t were increased by 25.9 times and 15 times. CONCLUSION Solid microneedle pretreatment of skin significantly improves in vitro penetration and in vivo skin absorption of ketoprofen patches through rat skin, with a more significant promotion effect in vivo penetration.

OBJECTIVE To optimize the formulation of nicorandil thermosensitive nasal gel (NIC-TNG) and further evaluate its quality. METHODS With gelling temperature and gelling time as observation indexes, the blank formulation composition of NIC-TNG was first optimized by central composite design-response surface method. Franz transdermal diffusion cell method was then used to screen the ideal permeation enhancer by using ex vivo nose mucosa of sheep as test model. The effect of pH on the chemical stability of NIC aqueous solution was investigated to establish the suitable pH of NIC-TNG. Lastly, NIC-TNG was prepared and its main quality items such as the gelation temperature and time, pH, labeled contents of the drug and preservative, cumulative erosion rate, cumulative drug release, and in vitro drug release were studied, respectively. Meanwhile, the effect of temperature on the viscosity, expansion coefficient and water holding capacity of NIC-TNG were investigated. RESULTS The optimized formulation of NIC-TNG consisted of 25 mg·mL^-1 NIC, 172.1 mg·mL^-1 F127, 5.0 mg·mL^-1 F68, 3.8 mg·mL^-1 HPMC, 5.0 mg·mL^-1 chlorobutanol and suitable amount of purified water. The gelation temperature and time, pH, labeled content of NIC and preservative were found to be 30.92 ℃, 40.82 s, 6.42, 99.18% and 98.72%, respectively. There was a good linear correlation between the in vitro cumulative erosion rate, cumulative drug release of NIC-TNG and time (r≥0.999 6). Furthermore, the in vitro release of NIC from the nasal gel showed obvious sustained release characteristics. Temperature exhibited obvious effect on the viscosity of the nasal gel. Finally, NIC-TNG showed low expansion coefficient and good water-holding capacity. CONCLUSION NIC-TNG will be expected to have good clinical application prospects due to its advantages such as reasonable formulation composition, simple preparation process, stable and controllable quality, convenient use and obvious sustained drug release behavior.

OBJECTIVE To establish a quantitative proton nuclear magnetic resonance (qHNMR) method for determination of the reference standards of moxifloxacin hydrochloride impurities A, B, C and D. METHODS Proton nuclear magnetic resonance (¹H-NMR) spectra of four reference standards of impurities were obtained in dimethylsulfoxide-d₆ (DMSO-d₆) or chloroform-d (CDCl₃) using a nuclear magnetic resonance spectrometer. The internal standard was 1,3,5-trimethoxybenzene. All ¹H-NMR spectra for quantitative analysis were measured with noesyigld1d pulse sequence using the following experimental parameters: 32 number of scans (NS), relaxation delay time (D1) of 30 s, 25 ℃ testing temperature. RESULTS The quantitative peak signals of four moxifloxacin hydrochloride impurities and 1, 3, 5-trimethoxybenzene were well separated on ¹H-NMR spectra, and the linear relationship was good within the linear range (r²>0.999 4). The injection precision and repeatability of the method were good. The contents of four reference standards of impurities determined by qHNMR method were basically consistent with those determined by mass balance method. CONCLUSION The established qHNMR method is accurate, reliable, simple, fast, which provides a new way for content determination of these impurities and can also be used as a mutual verification method for the calibration results of these reference substance by the mass balance method.

OBJECTIVE To establish a method for bacterial endotoxin test of active pharmaceutical ingredient (API) of insoluble adrenaline. METHODS According to the bacterial endotoxin test (BET) method in the general rule 1143 in the Chinese Pharmacopoeia (2020 Edition, Volume Ⅳ), adrenaline API was dissolved with hydrochloric acid and diluted with BET water. The gel method and kinetic turbidimetric assay were used to carry out interference test and endotoxin recovery interference verification test. RESULTS Adrenaline API was dissolved with 0.1 mol·L^-1 hydrochloric acid to 10 mg·mL^-1, and then diluted 200 times or more by BET water, which had no interference effects to bacterial endotoxin test. CONCLUSION The BET method established in this study can be used for the bacterial endotoxin test of adrenaline API of adrenaline to control the product quality.

OBJECTIVE To discuss the occurrence and clinical characteristics of Kounis syndrome (KS) induced by antibacterial drugs containing sulbactam in order to provide references for clinical safety drug use. METHODS The case reports of KS induced by antibacterial drugs containing sulbactam were retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP database from establishment of each database to October 2023. The relevant data were collected and analyzed. RESULTS A total of 11 cases from 11 articles were identified and included in the analysis. There were 7 males (63.6%) and 4 females (36.4%). The patients were aged from 44 to 89 years with an average age of (70.0±13.1) years old, and there were 9 patients aged 70 and above (81.8%). The drugs involved included cefoperazone sulbactam in 5 cases (45.5%), ampicillin sulbactam in 4 cases (36.4%) and piperacillin sulbactam in 2 cases (18.2%). The 81.8% of the patients developed acute anaphylaxis within 30 min after treatment and electrocardiogram indicated abnormal ST segment changes. Type Ⅰ, Ⅱ and Ⅲ KS were 8 cases (72.7%), 2 cases (18.2%) and 1 case (9.1%), respectively. After anti-allergic and anti-myocardial ischemia therapy, 10 patients (90.9%) had good prognosis, and 1 patient (9.1%) died of cardiogenic shock. CONCLUSION KS could be induced by a variety of antibacterial drugs containing sulbactam, especially in older patients and mostly within 30 min. KS should be highly suspected once acute anaphylaxis accompanied by abnormal changes in electrocardiogram. Timely withdrawal of medication and targeted treatment according to KS types are the key to improve the prognosis of patients.

OBJECTIVE To analyze the key contents of paediatric regulation in the European Union (EU) and identify the characteristics of the European regulation for paediatric medicines. METHODS A literature review was conducted to analyze the EU paediatric regulation, relevant guidance documents and published literatures. RESULTS The EU has established the paediatric medicines committee, which is specifically responsible for issues related to the regulation of paediatric medicines. Moreover, the EU has systematically designed the regulation around four aspects including obligations, rewards and incentives, other initiatives for paediatric medicines research and information and transparency measures. CONCLUSION The EU attaches great importance to building a professional team for the regulation of paediatric medicines, focusing on both mandatory and incentives, and emphasizing the concepts of the whole life cycle of medicines and dynamic adjustments, which provide a comprehensive guarantee for promoting the development and availability of paediatric medicines. It deserves to be studied and learned from.

OBJECTIVE To establish a method for preparing total saponins from Schizocapsa plantaginea Hance and establish a corresponding quality control method. METHODS The total saponins were extracted from the Schizocapsa plantaginea Hance tubers using a water bath reflux method, followed by purification of the crude extract through solvent extraction and macroporous resin. Subsequently, the purified product of total saponins of Schizocapsa plantaginea Hance(SSPHs) was prepared, and its quality was assessed using thin-layer chromatography, UV-visible spectrophotometry, and ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined method. RESULTS The developed preparation method resulted in a yield of total saponin products from the Schizocapsa plantaginea Hance tuber ranging from 0.29% to 2.81%, with a purity from 57.30% to 77.02%. After detection, saponin substances such as Schizocapsa Plantaginea Hance Ⅰ(SSPH Ⅰ) and Schizocapsa plantaginea Hance Ⅱ(SSPH Ⅱ) were found in the total saponin products. The content of SSPH Ⅰ was 10.77-85.60 mg·g^-1 and the content of SSPH Ⅱ was 0.19-4.75 mg·g^-1. CONCLUSION The established preparation method is simple, efficient, and environmentally friendly, with high product quality. The established qualitative and quantitative detection method can effectively reflect the quality of SSPHs and provide method reference for the quality control of SSPHs.

The development of oral delivery systems for protein and peptide drugs has long been the goal of the pharmaceutical field. However, extremely low bioavailability has been an unsolved problem in this research. This is related to the physical and chemical properties of the protein and peptides, as well as the three physiological barriers: the complex pH and enzyme environment after oral administration, the mucus barrier and the intestinal epithelial tissue barrier. With its porous rigid structure and high drug loading and strong stability, inorganic particle carrier has the ability to penetrate mucus and transport intestinal epithelia after surface modification, thus overcoming the three physiological barriers. This study introduces the current clinical application of protein and peptide drugs for oral administration, and the mechanism and coping strategies of physiological barrier that limit their oral absorption. Additionally, the application of inorganic materials as carriers in the oral delivery system of protein and peptide drugs are summarized.

Recently, chimeric antigen receptor (CAR)-T cell therapy has made remarkable success in hematological malignancies but faces a series of challenges in solid tumors. One of the major problems is that CAR-T cells overexpress programmed death-1 (PD-1) in tumor microenvironment. Therefore, blocking PD-1 can rescue the effector functions of CAR-T cells and reduce tumor burden significantly. Herein, it is aimed to summarize the progress in preclinical and clinical research on immunotherapy of combining CAR-T cells with PD-1 blockade for solid tumors.