Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers

Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Preparation and evaluation of sustained-release azithromycin tablets in vitro and in vivo

The objective of this study was to prepare azithromycin(AZI)sustained-release products in order to allow for a high dose to be administered,reduce gastrointestinal side-effects and increase the compliance of patients.AZI sustained-release tablets with different release performance(F-I:T_(100%)=3 h and F-II:T_(100%)=8 h in pH 6.0 phosphate buffer)were successfully prepared by wet granulation.The in vitro release rate and drug release mechanism were studied.The release rate of F-Iwas affected by dissolutionmedia with different pH,but not for F-II.HixsoneCrowellmodel was the best regression fitting model for F-I and F-II.Additionally,F-I and F-II both belonged to non-Fick diffusion.Oral pharmacokinetics of the two tablets and one AZI dispersible tablet as reference were studied in six healthy beagle dogs after oral administration.Compared with the reference,the C_(max) of F-I and F-II were decreased,and the T_(max) were prolonged,in that case which meet the requirement of sustained-release tablets.The relative bioavailability of F-I and F-II were 79.12%and 64.09%.T-test ofAUC_(0-144),and AUC_(0-∞) for F-I and F-II indicated there was no significant difference between F-I and F-II.These mean that the extended release rate did not induce different pharmacokinetics in vivo.

Clinical observation of Baitou Weng Decoction combined with mesalazine sustained-release tablets in treating heat-toxic and smoldering ulcerative colitis

Objective:To observe the clinical efficacy of Baitou Weng Decoction combined with mesalazine sustained-release tablets in the treatment of ulcerative colitis with febrile heat and its effect on immune function and serum inflammatory factors.Methods: A total of 84 patients with ulcerative colitis were randomly divided into control group and treatment group, with 42 cases in each group. The control group was given mesalazine sustained-release tablets orally, while the treatment group was given Baitou Weng Decoction and mesalazine sustained-release tablets orally. The treatment period was 30 days and the patients were followed up for 3 months. After treatment, the clinical efficacy, quality of life, immune function and serum inflammatory factors of the two groups were observed.Results: The effective rate of treatment group (90.47%) was higher than that of control group (73.81%) (P<0.05);compared with before treatment, the scores of inflammatory bowel disease quality of life questionnaire scale in both groups were significantly improved (P<0.05), and the difference between the two groups was significant (P<0.05);after treatment, the plasma CD4+/CD8+ ratio and NK+ levels in both groups were significantly higher than those before treatment (P<0.05), and the treatment group was changed. The serum levels of tumor necrosis factor-α, interleukin-17 and interleukin-23 were significantly decreased in both groups after treatment (P<0.05), and the improvement was more significant in the treatment group (P<0.05). No significant adverse reactions were observed in the treatment group.Conclusions: Modified Baitou Weng Decoction combined with mesalazine in the treatment of heat-toxic and incandescent ulcerative colitis can significantly improve the clinical efficacy, improve the quality of life of patients, effectively regulate the expression level of serum inflammatory factors in ulcerative colitis patients, promote the recovery of patients' immune function, and have high drug safety.

Clinical observation on treatment of cancer pain with TCM oriented drugs combined with oxycodone sustained-release tablets and nimesulide sustained-release tablets

Objective： To study the effect of the transdermal preparation of traditional Chinese medicine in treating cancer pain. Methods： From October 2016 to January 2018, 126 patients with cancer pain were enrolled and divided into 4 groups, 39 patients in group A （directed TCM permeation）, 26 patients in group B （oxycodone sustained-release tablets）, 32 patients in group C （Chinese medicine directed drug penetration ＋ oxycodone sustained-release tablets）, and 29 patients group D （Chinese medicine directed drug penetration ＋ oxycodone sustained-release tablets ＋ nimesulide sustained release tablets）, according to KPS scores. Results： Transdermal preparations of traditional Chinese medicine can significantly alleviate cancer pain. For the treatment of moderate to severe cancer pain, the Chinese medicine transdermal preparation can reduce the dosage of oxycodone sustained-release tablets. At the same time, the patient＇s KPS and NRS scores were significantly reduced. Moreover, the transdermal preparation of traditional Chinese medicine has a better therapeutic effect on visceral pain. Conclusion： The traditional Chinese medicine tra_nsdermal preparation combined with western medicine for the treatment of cancer pain may be a new method for the treatment of cancer pain.

Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

Simultaneous Analysis of Indapamide and Related Impurities in Sustained-Release Tablets by a Single-Run HPLC-PDA Method

The contents of indapamide and related impurities in generic indapamide sustained-release tablets were simultaneously detected by a single-run high performance liquid chromatography equipped with photodiode array detector(HPLC-PDA)method for the quality control in this paper.The results showed the method had a good selectivity and was validated through linearity,limits of detection and quantification,recovery,and precision.The linear ranges of indapamide,2-methyl-1-nitroso-2,3-dihydro-1H-indole(impurity A,ImA),4-chloro-N-(2-methyl-1H-indol-1-yl)-3-sulphamoyl-benzamide(impurity B,ImB)and 4-chloro-3-sulfamoylbenzoic acid(impurity 1,Im1)were 0.028-1.80μg/mL(R=0.99995),0.060-1.20μg/mL(R=0.9996),0.0324-1.20μg/mL(R=0.99985)and 0.060-1.20μg/mL(R=0.9997)with detection limits of 0.0093,0.012,0.012 and 0.006μg/mL,respectively.ImA and Im1 were not detectable in the generic drug.The content of indapamide was 96.7%of the labeled amount with a relative standard deviation(RSD)of 1.30%,and the percentage of ImB relative to the labeled amounts of indapamide was 0.106%with an RSD of 1.82%.The content of other unspecified impurities all met the reference quality standards.The results provided references for the quality control and the quality standard study of generic indapamide sustained-release tablets.

Qualitative and quantitative analysis of HPLC fingerprint of Wuji gastric floating sustained-release tablets

A qualitative and quantitative test method of fingerprint of Wuji gastric floating sustained-release tablets was established. High performance liquid chromatography （HPLC） was adopted, using Agilent ZORBAX SB-C18 column （250 mm×4.6 mm, 5 μm） as the chromatographic column, and acetonitrile-0.05 mol/L potassium dihydrogen phosphate solution as the mobile phase in a gradient elution with the flow rate of 1.0 mL/min. Sample solution （10 μL） was injected and was tested at the wavelength of 225 nm for 75 min at the column temperature of 30 ℃, Fingerprint similarity software （2004A version） was used to conduct data analysis. A total of 11 batches of Wuji gastric floating sustained-release tablets were tested and analyzed with HPLC fingerprint. Seventeen common peaks were found and the similarity of the 11 batches of agents was greater than 0.9, indicating that the production process of the agent is stable and feasible. The method is operable and could effectively control the quality of Wuji gastric floating sustained-release tablets.

咪唑斯汀缓释片仿制药与原研药质量对比研究

目的比较咪唑斯汀缓释片仿制药与原研药的质量。方法采用紫外-可见分光光度法测定制剂中咪唑斯汀的含量;以0.1 mol/L盐酸、0.01 mol/L盐酸、醋酸盐缓冲液(pH 3.8)及醋酸盐缓冲液(pH 4.5)为溶出介质,测定溶出度,并绘制溶出曲线;采用高效液相色谱法测定仿制药和原研药中有关物质含量。结果咪唑斯汀缓释片仿制药和原研药咪唑斯汀含量分别为标示量的98.19%~102.80%和100.70%~101.35%,相对偏差(RD)分别为0.29%~0.56%和0.21%~0.29%;两者在4种溶出介质中的溶出曲线差异较大,无法采用相似因子法对相关溶出度进行相似度评价;3批次仿制药中有关物质Ⅰ总量均为0.25%,有关物质Ⅱ总量分别为0.57%,0.54%,0.57%,3批次原研药中上述有关物质总量分别小于0.05%和0.10%。结论咪唑斯汀缓释片仿制药与原研药质量存在一定差异。建议有关厂家从制剂原料药及辅料、制备工艺等方面进行优化,提升仿制药质量,为仿制药一致性评价工作提供支撑。

咪唑斯汀缓释片稳定性分析法——HPLC法

目的 :建立咪唑斯汀缓释片的稳定性分析方法。方法 :采用高效液相色谱法。色谱柱为PhenomenexprodigyODS3 (2 5 0mm× 4 6mm ,5 μm) ;流动相 :甲醇 pH 4 0缓冲液 (7∶3) ;检测波长 2 80nm ;流速 1 0mL·min-1;外标法峰面积定量。结果 :咪唑斯汀保留时间约为 8 6min ,中间体、辅料、分解产物等对主药测定无干扰 ;咪唑斯汀浓度在 3～ 2 4 μg·mL-1范围内线性关系良好 ,回归方程为A =10 0 0 38 0 5C +6 5 5 6 ,r =0 99999;最低检出浓度为6 0ng·mL-1;日内、日间精密度 (RSD)分别为 0 39% (n =5 )和 0 5 6 % (n =5 ) ,重现性试验RSD =0 5 6 % (n =9) ;方法平均回收率为 99 4 7%～ 10 1 97% (n =5 ) ;模拟制剂平均回收率为 10 0 0 4 % (n =9)。结论 :该法灵敏、准确、专属性强 ,可用于咪唑斯汀片的稳定性研究。

两种咪唑斯汀缓释制剂体内生物利用度和药动学研究(英文)

目的对两种上市的咪唑斯汀缓释制剂进行人体药动学的研究,以评价两厂家生产的咪唑斯汀缓释片是否具有生物等效性。方法采用随机交叉试验设计,10名男性健康受试者单剂量口服咪唑斯汀缓释片(皿治林和尼乐)10mg后于规定时间点取血,用高效液相法测定血药浓度,计算两种缓释制剂的主要药动学参数,进行人体生物利用度的比较。结果10名男性健康受试者单剂量口服咪唑斯汀缓释片皿治林后的药动学参数分别为tmax为(1.70±0.59)h,cmax为(276.99±67.58)ng/mL,t1/2为(12.68±1.97)h,MRT为(15.29±2.67)h,AUC0→t为(2555.89±777.52)ng/mL·h,AUC0→∞为(2724.07±852.60)ng/mL·h;单剂量口服参比制剂尼乐后的药动学参数分别为tmax为(1.95±0.64)h,cmax为(344.56±93.96)ng/mL,t1/2为(12.42±1.89)h,MRT为(13.49±1.60)h,AUC0→t为(2532.28±776.06)ng/mL·h,AUC0→∞为(2659.16±818.06)ng/mL·h。统计结果表明药动学参数t1/2、MRT、tmax、AUC0→T、AUC0→∞受试制剂皿治林与参比制剂尼乐相比没有显著性差异,cmax具有显著性差异,与参比制剂cmax相比有所降低。AUC0→t、AUC0→∞、cmax、t1/2和MRT生物等效,tmax生物不等效。受试制剂的相对生物利用度平均为(101.26±9.82)%(n=10,以AUC0→t计算)和(102.52±8.61)%(n=10,以AUC0→∞计算);药动学参数cmax的比值为(82.17±15.32)%。结论受试制剂皿治林与参比制剂尼乐二者生物等效,但皿治林制剂咪唑斯汀峰浓度略低,达峰时间tmax略短。

花参合剂治疗血热证激素依赖性皮炎的临床疗效观察

[目的]观察花参合剂联合生理盐水湿敷治疗血热证激素依赖性皮炎的临床疗效。[方法]收集2018年7月至2019年7月上海曙光医院皮肤科门诊确诊的血热证激素依赖性皮炎患者64例,随机分为两组,每组各32例,治疗组给予花参合剂联合生理盐水湿敷,对照组给予咪唑斯汀缓释片联合生理盐水湿敷,观察两组患者总有效率与症状积分,并进行统计学分析。[结果]治疗4周后,治疗组患者总有效率为87.5%,对照组患者总有效率为81.3%,差异有统计学意义(P<0.05)。治疗后,两组患者症状积分均比治疗前低,差异有统计学意义(P<0.01)。治疗后,治疗组症状积分较对照组低,差异有统计学意义(P<0.05)。治疗结束2周后,治疗组症状积分略有升高,但差异无统计学意义(P>0.05);对照组症状积分有所升高,差异有统计学意义(P<0.01);治疗组症状积分比对照组低,差异有统计学意义(P<0.01)。[结论]花参合剂联合生理盐水湿敷治疗血热证激素依赖性皮炎疗效肯定,并可降低复发,安全可靠。

润燥止痒胶囊联合咪唑斯汀治疗老年瘙痒症疗效观察

目的:研究润燥止痒胶囊联合咪唑斯汀治疗老年皮肤瘙痒症的疗效。方法:将110例患者随机分为两组,,均患者均服用咪唑斯汀10mg,qd;治疗组加用润燥止痒胶囊4粒/次tid,疗程为4周。结果:治疗2周时治疗组和对照组患者有效率分别为65.51%和28.85%,两组有效率比较差异有统计学意义(P<0.05)。4周时治疗组有效率为91.38%;对照组有效率73.08%,两组比较差异有显著性(P<0.05)。结论:润燥止痒胶囊联合咪唑斯汀治疗老年皮肤瘙痒症疗效明显。

玉桂宁荨汤治疗风寒型荨麻疹的临床观察及对血清IL-6、IL-8及IFN-γ水平的影响

目的:探讨玉桂宁荨汤治疗风寒型荨麻疹的临床效果及其对血清IL-6、IL-8及IFN-γ水平的影响。方法:选取符合标准的72例患者随机分为两组,治疗组36例口服玉桂宁荨汤和对照组36例口服咪唑斯汀缓释片。同时观察两组患者治疗后的临床效果和复发率及血清IL-6、IL-8、IFN-γ水平。结果:经4周治疗后,玉桂宁荨汤组疗效评价优于对照组;两组的复发率对比,差异明显,有统计学意义(P<0.05)。玉桂宁荨汤组经治疗后第4周血清IL-6、IL-8及IFN-γ水平与咪唑斯汀缓释片组相比有统计学意义(P<0.05)。结论:玉桂宁荨汤治疗风寒型荨麻疹临床效果明显,并能降低血清IL-6、IL-8水平和提高血清IFN-γ水平,减小疾病复发率。

芩珠凉血合剂对湿疹患者外周血GRα受体的影响

目的观察芩珠凉血合剂对湿疹患者外周血GRα受体的影响。方法 60例湿疹患者随机分为2组。治疗组32例,予芩珠凉血合剂;对照组28例,予咪唑斯汀缓释片(皿治林),均口服治疗4周。检测患者治疗前后外周血GRα受体的含量,并与20例健康的正常人作对照,正常组20例均来自岳阳医院体检中心体检人群。结果 2组湿疹患者外周血GRα受体与正常组作比较,差异有统计学意义(P<0.05);芩珠凉血合剂组治疗前后外周血GRα受体含量比较有显著差异(P<0.05);皿治林组治疗前后外周血GRα受体含量比较无显著差异(P>0.05)。结论芩珠凉血合剂可以上调湿疹患者外周血GRα含量,皿治林对湿疹患者外周血GRα含量无明显改变。

反相高效液相色谱法测定咪唑斯汀片含量

目的 :建立咪唑斯汀片的含量测定方法。方法 :采用反相高效液相色谱法 ,色谱柱为C18,检测波长为285nm ,流动相为0. 025mol/L磷酸二氢钾缓冲液 -乙腈 (72∶28) ,流速为0. 5ml/min。结果 :咪唑斯汀检测浓度在4 .16～416μg/ml范围内线性关系良好 (r=0 .9998) ,平均加样回收率为99. 98 % (RSD=0. 44 % ,n=3)。结论 :本法可用于咪唑斯汀片的含量测定 ,且操作简便、结果准确。

润燥止痒胶囊联合咪唑斯汀缓释片对慢性湿疹的治疗效果观察

目的探讨润燥止痒胶囊联合咪唑斯汀缓释片治疗慢性湿疹的临床效果。方法按照随机数字表法将收治的98例慢性湿疹患者分为两组,对照组49例,采用咪唑斯汀缓释片治疗,观察组49例,在对照组的基础上联合润燥止痒胶囊治疗,对比两组疗效。结果观察组治疗总有效率优于对照组(P<0.05);且观察组患者治疗后症状评分优于对照组(P<0.05);两组不良反应发生情况比较差异无统计学意义(P>0.05)。结论采用润燥止痒胶囊联合咪唑斯汀缓释片治疗慢性湿疹患者效果显著。

贞芪扶正颗粒联合咪唑斯汀缓释片治疗慢性泛发性湿疹疗效观察

目的:观察贞芪扶正颗粒联合咪唑斯汀缓释片治疗慢性泛发性湿疹的临床疗效。方法:筛选符合入组条件的95例慢性泛发性湿疹患者,随机分为两组。治疗组(A组)47例,应用贞芪扶正颗粒联合咪唑斯汀缓释片口服治疗14天。对照组(B组)48例,口服咪唑斯汀缓释片治疗14天。两组患者均外用卤米松乳膏,连续治疗14天。两组分别记录14天症状、皮疹变化。结果:治疗组有效率为85.1%,复发率16.13%;对照组有效率58.3%,复发率33.33%。两组比较差异有统计学意义(P<0.05)。结论:贞芪扶正颗粒联合咪唑斯汀缓释片治疗慢性泛发性湿疹效果较好,且无明显不良反应。

中西医结合治疗慢性湿疹临床研究

目的探讨复方甘草酸苷片联合四物消风饮治疗慢性湿疹临床疗效和安全性。方法入选的82例慢性湿疹患者随机分为两组,各41例。治疗组采用复方甘草酸苷片联合四物消风饮治疗,对照组采用咪唑斯汀缓释片治疗。两组均外用尿素软膏治疗。连续治疗1月后观察临床疗效。结果治疗组总有效率为87.80%,对照组为68.29%,两组比较,有显著性差异(P<0.05)。结论复方甘草酸苷片联合四物消风饮治疗慢性湿疹疗效显著,且不良反应少。

润燥止痒胶囊与咪唑斯汀缓释片在慢性湿疹临床治疗中的应用效果

目的探析润燥止痒胶囊以及咪唑斯汀缓释片在慢性湿疹中的应用意义。方法选取青县人民医院2019年1月至2020年1月收治的80例慢性湿疹患者作为研究对象。以随机数字表法方完成分组,将应用咪唑斯汀缓释片治疗的40例患者设立为对照组,将应用润燥止痒胶囊联合咪唑斯汀缓释片治疗的40例患者设立为观察组,疗程结束时开展指标对比。结果观察组总有效率更高,与对照组差异有统计学意义(P<0.05)。治疗前两组症状积分相当,差异无统计学意义(P>0.05);治疗后观察组症状积分更低,与对照组差异有统计学意义(P<0.05)。结论联合润燥止痒胶囊以及咪唑斯汀缓释片治疗慢性湿疹,疗效确切,有利于缓解患者病情症状,应用价值显著。