Journal of Chinese Pharmaceutical Sciences

The preparation and characterization of sustained-release solid dispersion of resveratrol by hot-melt extrusion technology

Meiqi Gao, Jiali Wu, Wenjing Zhu, Xiaotong Zhang, Wenling Fan

2023, 32(3): 165-179. DOI: 10.5246/jcps.2023.03.014

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In the present study, we aimed to prepare, characterize, and evaluate the capability of solid dispersion (SD) for resveratrol (RES) with low solubility and high melting points. A sustained-release solid dispersion (SRSD) was prepared by hot melt extrusion (HME). The release of RES was controlled using a hydrophobic-hydrophilic polymer mixture (Eudragit RS and Poloxamer 188). The effects of formula and process parameters were systematically studied by univariate analysis. Then the Box-Behnken design (three factors, three levels) was used to optimize the preparation process of SRSD. Differential scanning calorimetry and X-ray diffraction were adopted to determine the physical state of SD. Scanning electron microscopy was used to observe its surface properties, and Fourier transform infrared spectroscopy was used to explore chemical interactions between excipients. Dissolution studies were carried out to investigate the kinetics and drug release time. In vitro studies showed that RES release followed the Weibull model kinetic. RES SRSD (RESRS P188-SRSD) was successfully prepared using HME, in which the mass ratio of the drug to the carrier was 1:3, the release regulator was P188, and the dosage was 10%. The stability of the preparation was good, and the dissolution was increased by 10 times.

A study of irritable bowel syndrome model construction based on combined factor stimulation

Xinfeng Zou, Haihua Guo, Liangjun Deng, Yuting Yang, Zhengqiang Yuan, Wen Tan

2023, 32(3): 180-189. DOI: 10.5246/jcps.2023.03.015

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To establish a model with a short modeling period and consistent with the pathogenesis of IBS, chronic stimulation and chemical stimulation were combined. In the present study, we aimed to establish a novel model of irritable bowel syndrome (IBS) and investigate its feasibility. Chronic unpredictable stimulation was used as a single factor model, and its addition with glacial acetic acid stimulation was used as a comprehensive factor model. The symptoms of the IBS model were analyzed from a collection of tests, including body weight, essential food consumption, sucrose consumption, fecal grain number, Bristol score, abdominal withdrawal reflex, open field tests, elevated cross-maze tests, intestinal transportation time, and H&E staining. The results showed that compared with the single-factor model and the control groups, the rats in the comprehensive model group exhibited less body weight, reduced food consumption, decreased sucrose consumption, increased fecal grain number, decreased Bristol score and pain threshold, and significantly reduced physical activity. The comprehensive factor group model conformed to the complex pathogenesis of IBS and thus had a significant effect on it, which could be used to establish an effective IBS model.?Furthermore, the modeling effect was significantly evident in male rats compared with female ones.

Warfarin affects the proliferation and apoptosis of lung cancer cells by regulating the Gas6/Axl/PI3K/Akt/NF-κB pathway

Limei Yang, Liman Wang, Xuhui Huang, Jie Zhuang

2023, 32(3): 190-199. DOI: 10.5246/jcps.2023.03.016

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The antitumor potential of warfarin is demonstrated in different experimental cancer model systems. However, the mechanism of warfarin in reducing the incidence of lung cancer is unclear. In the present study, we aimed to investigate the effect and the possible mechanism of warfarin on the proliferation and apoptosis of lung cancer cell line H226. It was an in vitro experiment. The lung cancer cell line H226 was intervened with warfarin at the concentrations of 128, 256, and 512 μmol/L. The cell proliferation was determined by CCK8 assay, and the cell apoptosis was evaluated by flow cytometry and Western blotting analysis. The effects of warfarin on Gas6/Axl/PI3K/Akt/NF-κB protein and gene expression were determined by Western blotting analysis and RT-PCR, respectively. Warfarin inhibited the growth of H226 cells at 24, 48, and 72 h, showing a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of H226 cells was significantly increased when treated with 128, 256, and 512 μmol/L warfarin. Meanwhile, the expression of Bcl-2 protein was decreased, and the expressions of Bax protein and Caspase 3 protein were increased, showing significant differences compared with the blank group (P < 0.05). Compared with the control group, warfarin and Axl inhibitor BGB324 could inhibit the protein expression of the Gas6/Axl pathway and its downstream pathway (P < 0.05) significantly and decrease the gene expression of the Gas6/Axl/PI3K/Akt/NF-κB pathway significantly (P < 0.05). Warfarin could inhibit the proliferation and induce the apoptosis of the lung cell line. The possible mechanism might be related to the inhibitory effect on Gas6/Axl/PI3K/Akt/NF-κB pathway proteins and genes.

Effect of vitamin D supplementation on metabolic syndrome: a retrospective study

Jing Yang, Xin Wang, Zihui Wang, Xiaojia Yu, Huaguang Wang, Ying Zhu, Boyu Li, Shuang Qiu, Zhuoling An

2023, 32(3): 200-206. DOI: 10.5246/jcps.2023.03.017

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Vitamin D supplementation can improve metabolic syndrome (MetS)-related indicators. In the present study, we aimed to explore whether this improvement was dose-dependent in patients with low 25(OH)D levels. A retrospective study that recruited MetS patients from January 2017 to June 2019 was undertaken. They were divided into three groups according to the basic level of 25(OH)D. Chi-square test, one-way ANOVA, and T-test were used to examine the differences. A total of 111 patients were included in this study. The average age of them was 62.21 ± 13.35 years (21–89 years), and the mean serum 25(OH)D was 14.67 ± 5.75 nmol/L (4.6–27.5 nmol/L). After 29.92 ± 2.72 d, the serum 25(OH)D of each group was significantly increased (P < 0.05). The SBP, TG, and LDL-C were significantly decreased (P < 0.05), while TC and FBG were unaffected. There was no difference between the three groups (P > 0.05). Increasing the level of 25(OH)D could alleviate the pain caused by statins, even though the results of the statin gene suggested that the risk of myalgia was high. Taken together, vitamin D supplementation was beneficial for patients with MetS, and the benefit was not dose-related.

The effects of midazolam combined with dezocine on laparoscopic appendectomy

Changping Lin, Sanyue Wang, Yunguo Xue, Youliu Yu

2023, 32(3): 207-213. DOI: 10.5246/jcps.2023.03.018

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In the present study, we aimed to investigate the effect of midazolam combined with dezocine on anesthesia induction before laparoscopic appendectomy. A total of 107 patients with appendicitis in our hospital from June 2018 to March 2021 were randomly divided into the control group (53 cases) and the observation group (54 cases). The control group was given midazolam, and the observation group was given midazolam combined with dezocine. The vitals, analgesia, sedation indexes, and adverse reactions of the two groups were compared. Compared with time T0, HR and MAP at T1, T2, T3, and T4 in both groups were decreased (P < 0.05), while there was no significant change in T1–T4 in the two groups, respectively (P > 0.05). MAP of the observation group was lower than that of the control group at the T1–T4 time points (P < 0.05). SPO₂ showed no significant change at all time points (P > 0.05). The NRS score at 6 h after surgery of the observation group (3.52 ± 1.28 scores) was significantly lower compared with the control group (4.26 ± 1.76 scores, P < 0.05). The Ramsay sedation score at 1 h after surgery of the observation group (2.32 ± 0.78 scores) was significantly higher compared with the control group (1.73 ± 0.65 scores, P < 0.05). Moreover, there was no significant difference in the incidence of adverse reactions between the observation group (7.4%) and the control group (11.3%, P > 0.05). Collectively, midazolam combined with dezocine could better reduce postoperative MAP and postoperative pain in patients with laparoscopic appendectomy, showing good postoperative sedation effect and safety.

Evidence-based pharmacoeconomic evaluation of palbociclib in combination with letrozole versus docetaxel in combination with epirubicin in the first-line treatment of advanced breast cancer with epirubicin

Ciyan Peng, Jing Chen, Sini Li, Jianhe Li, Liubao Peng

2023, 32(3): 214-222. DOI: 10.5246/jcps.2023.03.019

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In 2015, palbociclib became the first FDA-approved CDK4/6 selective small-molecule tyrosine kinase inhibitor (TKI). CDK4/6 inhibitors have shown significant effects on inhibiting tumor growth, halting disease progression, and improving survival in patients with advanced HR+/HER2-breast cancer. In the present study, we evaluated the effectiveness and affordability of palbociclib in combination with letrozole compared with docetaxel in combination with epirubicin in the first-line treatment of advanced breast cancer by Bayesian analysis and Markov modeling. The results showed that the progression-free survival (PFS) of docetaxel in combination with epirubicin versus palbociclib in combination with letrozole for advanced HR+/HER2-breast cancer was: HR = 1.8, 95% CI = 0.49–5.68, P < 0.1, and the overall survival (OS) was: HR = 1.5, 95% CI = 0.62–5.90, P < 0.1; 3.55 LYs were obtained in the palbociclib combined with letrozole group, with an increase of 0.68 LYs over the docetaxel combined with epirubicin group. The ICER was ￥ 91 494 QALY^–1, which was lower than the national WTP (￥ 161 940 QALY^–1). The results were basically consistent with the results of the primary analysis, indicating that the results of the fundamental analysis were more stable. Palbociclib in combination with letrozole was more effective and economical than docetaxel in combination with epirubicin in the first-line treatment of advanced breast cancer, which deserves clinical attention.

The introduction of nitrosamine impurities in medicinal products

Jianzhao Niu, Dongsheng Yang, Yufei Feng, Baihao Sun, Haoyue Guan, Lingyun Ma

2023, 32(3): 223-230. DOI: 10.5246/jcps.2023.03.020

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Nitrosamine impurities being reported to potentially present in medicinal products are the new hot issues in the pharmaceutical field during recent years. Five classes of medicinal products are being reported due to the possible presence of nitrosamine impurities: Sartan medicines, Metformin-containing medicines, Ranitidine medicines, Rifampicin medicines, and Champix. In this paper, we introduced the source and potential root causes of nitrosamine formation, potential or founded nitrosamine impurities in API and medicinal products, and acceptable intake limits recommended for those impurities. Moreover, we also summarized the current nitrosamine impurities concerned with medicinal products and corresponding control strategies adopted by the FDA and EMA, and it is expected to give reference for the Chinese or foreign pharmaceutical enterprises, as well as the regulatory authority, to get the comprehensive understanding of the nitrosamine impurities in the medicinal products.

Medicinal Chemistry and Drug Development Cases is published edited by Professor Gang Liu from the School of Pharmaceutical Sciences, Tsinghua University

Journal of Chinese Pharmaceutical Sciences

2023, 32(3): 231-233.

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