Current Drug Delivery
·
2021
·Vol. 18
·期 3
·357-368
·
IF 2.565
Liang Yutong,Zhang Jiaojiao,Zhao Xinghua,Wang Ming,Ding Shi,Wang Yang,Chen Ye,Liu Ju
Purpose: The purpose of this study is to develop a new PLGA based formulation for microspheres, which aims to release mometasone furoate for one month, so as to improve compliance. Methods: The microspheres containing mometasone furoate were prepared by oil in water emulsion and
solvent evaporation. The microspheres were characterized by surface morphology, shape, size and encapsulation efficiency. The release in vitro was studied in 37°C phosphate buffer, and in vivo, pharmacodynamics and preliminary safety evaluation were conducted in male Sprague Dawley rats.
Results: The morphology results showed that the microspheres have a smooth surface, spherical shape and an average diameter of 2.320-5.679μm. The encapsulation efficiency of the microspheres loaded with mometasone furoate was in the range of 53.1% to 95.2%, and the encapsulation efficiency
of the microspheres could be greatly affected by the proportion of oil phase to the water phase and other formulation parameters. In vitro release kinetics revealed that drug release from microspheres was through non-Fick's diffusion and PLGA polymer erosion. Pharmacokinetic data showed that
the initial release of microspheres was small and then sustained. The results of the pharmacodynamics study fully proved the long-term effectiveness of mometasone furoate microspheres. The results of in vivo safety evaluation showed that the preparation system possessed good in vivo safety.
Conclusion: This study shows that the microspheres prepared in this study have sufficient ability to stable drug release at least for 35 days, with good efficacy and high safety. In addition, mometasone furoate can be used as a potential candidate drug for 35 days long-term injection.
研究领域:
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Yue-Ming Yu,Fan-Zhi Bu,Su-Su Meng,Cui-Wei Yan,Zhi-Yong Wu,Yan-Tuan Li
To emphasize the superiority of uracil (UR) in ameliorating biopharmaceutical characteristics of marine antitumor medicine cytarabine (ARA), thus gaining some innovative opinions for the exploitation of nanococrystal formulation, a cocrystal nanonization strategy is proposed by integrating cocrystallization and nanosize preparation techniques. For one thing, based on UR's unique structural features and natures together with advantages of preferential uptake by tumor cells, cocrystallizing ARA with UR is expected to improve the in vitro / vivo performances. For another, the nanonization procedure is oriented towards maintaining the long-term effective drug level. Along this route, a cocrystal of ARA with UR, viz ., ARA-UR, is successfully synthesized and then transformed into nano-cocrystal. The cocrystal structure is precisely confirmed by various methods, demonstrating that a 1:1 ARA and UR in the crystal forms cytosine-UR hydrogen-bonding interactions, thus constructing supramolecular frameworks by strong π-π stacking interplays; while the nano-cocrystal is block-shaped particles of 562.70 nm with zeta potential −33.40 mV. The properties of cocrystal ARA-UR and its nano-cocrystal in vitro / vivo are comparatively explored by theoretical calculations and experimental analyses, revealing that permeability of both is significantly increased than ARA per se . Notably, the meliorative natures of both the cocrystal and nano-cocrystal in vitro bring excellent antitumor activity , but the latter has greater strengths over the former. More notably, the nano-cocrystal can sustain effective concentration for a relatively longer time, causing lengthened retention time and better absorption in vivo . The contribution offers a fire-new dosage form of ARA for long-lasting delivery, thus filling the vacancy in nanococrystal studies about marine drugs.
研究领域:
药剂学
·
纳米技术
·
药物递送系统
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES
·
2021
·
IF 1.312
Huanhuan Li,Xuan Yu,Guoqin Zhang,Zhiying Dou,Meng Wang,Yanan Liu,Xiaoliang Ren,Chao Li
Adverse reactions that occur following the injection of traditional Chinese medicines may limit clinical use. A systematic investigation of methods to ensure the safety and stability of traditional Chinese medicine injection was performed using Shenmai Injection as an example. High-performance liquid chromatography with diode-array detection, high-performance liquid chromatography with evaporative light scattering detector, and chemical kinetics were used to study the degradation of the active ingredients (ginsenosides), pharmaceutical excipient (polysorbate 80), and carbohydrates (sucrose, glucose, and fructose) under a variety of pressure conditions (pH, temperature, light, oxidation, and starting concentrations). The main factors affecting the degradation of the ingredients in Shenmai Injection were determined by comparing the differences in the degradation rules of the ingredients in the aqueous solution and Shenmai Injection. Changes in pH of Shenmai Injection were monitored to preliminarily explore the main material factors that lead to its acidification. The results showed that with a pH of <4, the degradation of ginsenosides was accelerated with the enhancement of acidity. In acidic or neutral conditions, the degradation rate of ginsenosides increased with temperature. Alkaline environment, light, and different initial concentrations had no significant effect on the degradation of ginsenosides. For pharmaceutical excipient, increased alkalinity accelerated the degradation of polysorbate 80, which was promoted at high temperatures. The content of polysorbate 80 was almost unchanged in neutral, acidic, and light conditions. The excipient polysorbate 80 had no significant effect on the stability of ginsenosides under acidic or high-temperature conditions. Monosaccharides like glucose and fructose underwent epimerization under certain conditions, and sucrose was hydrolyzed to monosaccharides. Polysorbate 80 and carbohydrates could decrease the pH of the solution under high-temperature conditions, and the acidification of Shenmai Injection was accelerated as the temperature increased. In conclusion, we established a multi-ingredient, multi-factor stability research method. The main factors affecting the degradation of ingredients were clarified, and the stability-related factors causing acidification of Shenmai Injection were preliminarily explored.
研究领域:
药学
·
中药学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 17
·10338-10351
·
IF 3.119
Libing Chen,Fang Zhao,Wenzhu Li,Zeqi Chen,Jianyang Pan,Difeifei Xiong,Bailing Li,Qingjie Zhang,Haibin Qu
This paper evaluates a multiple and global analytical indicator of batch consistency in traditional Chinese medicine injections (TCMIs) via a chemometrics tool, which is more comprehensive to appraise quality consistency of different batches of injections than the traditional method of fingerprint similarity. A commonly used TCMI, Salviae miltiorrhizae and ligustrazine hydrochloride injection (SLI), was employed as a model. With the aid of a chemometrics tool (principal component analysis, PCA), evaluation of multiple and global analytical indicators of batch consistency, which included saccharides, phenolic acids and inorganic salts (18 indicators in total), was carried out to appraise the quality consistency of 13 batches of injection provided by the Guizhou Baite Pharmaceutical Co., Ltd. (Guizhou, China). Compared with the traditional HPLC-UV fingerprint similarity evaluation, the method proposed in the paper can more comprehensively and correctly reflect the quality consistency of different batches of injections. In this paper, the multi-index evaluation result showed poor batch consistency, which was more consistent with the determination results, while the fingerprint similarity evaluation results still showed good batch consistency. The HPLC-UV fingerprint reflects only substances with UV absorption, but it is not able to reflect substances without UV absorption or weak UV absorption, which leads to inappropriate conclusions. Therefore, quality consistency of injections can be effectively appraised by evaluation of multiple and global analytical indicators, instead of HPLC-UV fingerprint only. For visualizing the batch consistency of the multiple and global analytical indicators, a heat map was used to represent the fluctuation. Furthermore, critical indicator identification was also applied to select several indicators that should be paid more attention during the process of quality control of injection. And the analysis result showed that Na+, fructose (Fru), glucose (Glc), manninotriose (Man), danshensu (DSS) and salvianolic acid B (SAB) are the indicators that should be given more attention when controlling the quality of injections, also called critical quality control indicators. The proposed method provides a reference for the quality control of TCMIs and has broad application potential.
研究领域:
中药学
·
分析化学
·
制药工程
✓ 已验证
DOI
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 4
·1-11
·
IF 3.3
Li Shuo,He Ying,Sun Dianjun,Wang Zhaomeng,Yu Jiang,Ye Jianying,He Zhonggui,Wang Yongjun
Latuda® is an oral tablet approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. However, the clinical efficacy of Latuda® is compromised by patient noncompliance due to frequent daily administration, especially for patients experiencing severe schizophrenia, whose medication is often needed for several months to years. Hence, developing a long-acting injectable formulation of lurasidone is urgently needed. Herein, a poorly water-soluble lurasidone pamoate (LP) salt was synthesized via the facile ion pair-based salt formation technology. The solubility of LP was decreased by 233 folds compared with that of lurasidone hydrochloride (LH). Furthermore, suspensions of LH and LP with three different particle sizes, including 400 nm small-sized nanocrystals (SNCs), 4 μm medium-sized microcrystals (MMCs), and 15 μm large-sized microcrystals (LMCs) were prepared and characterized by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The in vitro release results showed that particle sizes had great effects on the sustained release of LH, where large-sized particles exhibited superior sustained release than the smaller ones. Besides, LP suspensions exhibited better sustained release than LH suspensions at the same size scale. Moreover, the pharmacokinetics showed that LP LMCs produced an extended in vivo intramuscularly injectable profile for up to 45 days, which was 10 days longer than that of the LH LMCs. Our findings demonstrated that particle size had appreciable impacts on drug sustained release and provided valuable knowledge for the rational design of optimized micronized suspensions for long-acting injectables. Graphical
研究领域:
药剂学
·
药物传递
·
药代动力学
·
生物药剂学
·
纳米技术
✓ 已验证
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2017
·Vol. 41
·期 15
·7133-7141
·
IF 3.269
Yue Hu,Wei Huang,Yukui Tong,Qinfei Xia,Miaomiao Tian
Boronate-affinity hollow molecularly imprinted polymers (h-MIPs) were prepared and applied to the selective enrichment of four nucleosides in traditional Chinese medicine injection samples, followed by HPLC detection. The synthesis mechanism of the h-MIPs was studied. Due to a large amount of boronic acid groups were introduced by 3-aminophenylboronic acid (APBA) in the outermost polymer shell of the MIPs, which was of great importance for improving the enrichment efficiency of the nucleosides. Furthermore, owing to the hollow structure of the h-MIPs, more binding cavities were located on the inner and outer surfaces of the h-MIPs, which could facilitate the removal of template molecules from the polymers and the rebinding of the target molecules to the polymers. Under optimal conditions, the detection limits of the four nucleosides were in the range of 0.012–0.033 μg mL−1. At the different spiked levels, the recoveries of the nucleosides were in the range of 63.8–108.9%. The proposed method was successfully applied to determine four nucleosides in five injection samples. The boronate-affinity h-MIPs provided a promising selective enrichment platform for precise nucleoside analysis.
研究领域:
分析化学
·
药物分析
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL LETTERS
·
2019
·
IF 1.248
Jie Jiang,Dongmei Zhang,Dandan Zhao,Lina Qiao,Na Li,Kai Yu,Jing He,Hong Zhang
Rapid analysis of pharmaceutical preparations is of great interest in clinical studies with benefits for identifying counterfeit drugs. In this study, droplet spray ionization tandem mass spectrometry (DSI-MS/MS) was developed for the rapid determination of adenine arabinoside monophosphate in pharmaceutical injections without complex sample pretreatment. The sample solution was loaded on the slip corner placed in front of the inlet of a mass spectrometer, and high voltage was applied to the solution to create a charged spray from the corner for MS analysis. The sample was loaded for analysis without additional sample preparation protocols, which greatly simplifies the operation. The limit of detection and limit of quantification were determined to be 2.7 and 9.1 ng/mL, respectively. The recoveries were in the range from 96% to 112%, and the calculated relative standard deviations were less than 7% for the DSI-MS/MS method. Three adenine arabinoside monophosphate pharmaceutical injection samples and a degraded sample obtained by acid treatment at 40 °C were successfully analyzed by directly dissolving and diluting the sample. Moreover, the sample-loading step required only 2 s. Together these capabilities indicate that the DSI-MS/MS is a simple and robust method and has promising applications in pharmacology studies without complicated sample pretreatment.
研究领域:
药学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2014
·Vol. 7
·期 2
·708-715
·
IF 1.938
Wenlong Liao,Anyi Chen,Yaling Yang
A simple and effective method based on magnetic solid-phase extraction combined with high performance liquid chromatography was used for the determination of hindered phenolic antioxidants in plastic packaging injections. The extraction and clean-up via Fe3O4@CTAB magnetic adsorbent dispersion in injections was followed by magnetic isolation and desorption of the analytes using acetonitrile. The cationic surfactant cetyltrimethylammonium bromide (CTAB) coated on the surface of Fe3O4 nanoparticles adsorbent was synthesized. The main parameters affecting the adsorption recoveries were evaluated and optimized, including the amounts of surfactant and adsorbent, pH, ionic strength, desorption conditions, and sample volume. Under the optimum conditions, the method was successfully applied to the determination of hindered phenolic antioxidants in plastic packaging injections. Low limits of detection (LODs) of 0.14 and 0.15 µg mL−1 and limits of quantification (LOQs) of 0.45 and 0.50 µg mL−1 were achieved. The mean recoveries were in the range from 85.0% to 93.5% at 5, 10, and 20 µg mL−1 spiked levels, and the relative standard deviations (RSDs) were in the range from 1.16% to 2.81%.
研究领域:
分析化学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
AAPS PHARMSCITECH
·
2017
·Vol. 19
·期 2
·541-550
·
IF 2.451
Liu Daichun,Galvanin Federico,Yu Ying
The purpose of this study was to prepare ginkgolide B (GB) lyophilized powder for injection with excellent appearance and stable quality through a formulation screening and by optimizing the freeze-drying process. Cremophor EL as a solubilizer, PEG 400 as a latent solvent, and mannitol as an excipient were mixed to increase the solubility of GB in water to more than 18 times (about from 2.5 × 10 −4 mol/L (0.106 mg/mL) to 1.914 mg/mL). Formulation screening was conducted by orthogonal design where the content of GB in the solution before lyophilization (using external standard method of HPLC) and reconstitution time after lyophilization were the two evaluation indexes. The optimized formulations were GB in an amount of 2 mg/mL, Cremophor EL in an amount of 16% ( v / v ), PEG 400 in an amount of 9% ( v / v ), mannitol in an amount of 8% ( w / v ), and the solution pH of 6.5. Through four single-factor experiments (GB adding order, preparation temperature of GB solution, adding amount, and adsorption time of activated carbon), the preparation process of GB solution was confirmed. The glass transition temperature of maximally GB freeze-concentrated solution was − 17.6°C through the electric resistance method. GB lyophilized powder began to collapse at − 14.0°C, and the fully collapsed temperature was − 13.0°C, which were determined by freeze-drying microscope. When the collapse temperature was determined, the primary drying temperature was obtained. Thereby, the freeze-drying curve of GB lyophilized powder was initially identified. The freeze-drying process was optimized by orthogonal design, the qualified product appearance and residual moisture content were the two evaluation indexes. The optimized process parameters and process were (1) shelf temperature, decreased from room temperature to − 45.0°C, at 0.5°C/min in 2 h; (2) shelf temperature increased from − 45.0 to − 25.0°C, at 0.1°C/min, maintained for 3 h, and the chamber pressure was held at 10 Pa; (3) shelf temperature was increased from − 25.0 to − 15.0°C at 0.1 °C/min, maintained for 4 h, and the chamber pressure was held at 10 Pa; and (4) shelf temperature was increased from − 15.0 to 20.0°C at 1.0 °C/min, maintained for 4 h, and the chamber pressure was raised up to 80 Pa. In these lyophilization process conditions, the products complied with relevant provisions of the lyophilized powders for injection. Meanwhile, the reproducibility was satisfactory. Post-freezing annealing had no significantly beneficial effects on shortening the freeze-drying cycle and improving the quality of GB lyophilized powder.
研究领域:
药学
·
药剂学
·
药物传递系统
·
制药技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Shen Yunfu,Guo Kaiqiang,Ma Aijun,Huang Zhe,Du Jingjing,Chen Junhe,Lin Qianyu,Wei Chengming,Wang Zi,Zhang Fuming,Zhang Juan,Lin Wanjun,Feng Na,Ma Wenzhe
There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.
研究领域:
药理学
·
毒理学
·
中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2024
·Vol. 47
·期 1
·2300545
·
IF 2.8
Chen Yang,Jing-Wen Zhang,Jin Qi,Bo-Yang Yu
Pseudoallergy is a typical and common adverse drug reaction to injections, especially in traditional Chinese medicine injections (TCMIs). At present, the evaluation methods for pseudoallergy include cell methods in vitro and animal methods in vivo. The mast cell evaluation method based on the β-hexosaminidase (β-Hex)-catalyzed substrate, 4-nitrophenyl-β-N-acetyl-D-glucosaminide (4-NPG), is an important method for the evaluation of drug-induced pseudoallergy, but it is prone to false positive results and has insufficient sensitivity. In this study, a novel β-Hex evaluation system with rat basophilic leukemia-2H3 cells based on high-performance liquid chromatography-fluorescence detection (HPLC-FLD) was established, which effectively increased the sensitivity and avoided false positive results. Cell viabilities were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay. In addition, a method for the determination of histamine, which is another indicator in the development of pseudoallergy, was established to validate the above method. The results of this novel method indicated that two TCMIs (Shuxuening injection and Shenqi Fuzheng injection), which were considered to be pseudoallergenic using 4-NPG, were not pseudoallergenic. Overall, the novel β-Hex/HPLC-FLD evaluation system using Rat basophilic leukemia-2H3 cells established was effective and precise. It could be used for the evaluation of pseudoallergic reactions caused by TCMIs and other injections.
研究领域:
药理学
·
免疫学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
·
IF 4.8
Qin Guo,Jie Cai,Pengyu Li,Dongling Xu,Xiaomin Ni,Hui Wen,Dan Liu,Suizhen Lin,Haiyan Hu
Androst-3β,5α,6β-triol (Triol) is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC) after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of drug-loaded mixed micelles.
研究领域:
药剂学
·
药物化学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）