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.

Formulation Development and Evaluation of Poorly Water Soluble Gliclazide Tablet Containing Aerosil 380 as Carrier

The core objective of the current work was to improve dissolution rate of poorly water-soluble anti-diabetic drug gliclazide by solid dispersions (SDs) technique using fumed silica particles Aerosil 380 as carrier into compressed tablets. Different FGA-1, FGA-2, FGA-3 (Formulated Gliclazide Aerosil;weight ratio, 1:1) and FPG-1, FPG-2 (Formulated Plain Gliclazide) tablet batches were formulated, prepared, evaluated and characterized. All the findings of pre-compression factors were found to be satisfactory and post-com- pression parameters revealed good mechanical integrity and good uniformity in all formulations. All the formulated tablets satisfied the compendia limits of weight variation, friability and the disintegration time. Among all formulations, FGA-3 was optimized based on in vitro drug release findings, disintegration time, hardness and other quality attributes. The percent of drug release from the formulated FGA tablets containing gliclazide loaded aerosil is about 3 fold higher when compared with the tablets formulated and prepared with plain gliclazide (FPG) and the tested commercial brands in first 60 minutes. There was no significant change noted in the drug content and drug release pattern in the FGA tablets batches when stored in 40℃?and 75% RH for three months. It was thus concluded that SDs formulations of gliclazide could be successfully used to design and develop a solid dosage form of the drug, which would have significant benefits over the existing commercial brands.

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.

恩格列净片与格列奇特缓释片联用治疗对2型糖尿病患者血糖指标及不良反应情况的影响

目的探讨恩格列净片与格列奇特缓释片联用治疗对2型糖尿病患者血糖指标及不良反应情况的影响。方法选取2023年1—12月厦门市第三医院收治的70例2型糖尿病患者为研究对象,随机数表法分为两组,各35例。对照组以恩格列净片治疗,观察组以恩格列净片与格列奇特缓释片联合治疗,分析两组临床数据。结果观察组治疗后空腹血糖、餐后2 h血糖与糖化血红蛋白水平低于对照组,差异有统计学意义(P均<0.05);观察组治疗后低密度脂蛋白胆固醇、总胆固醇、三酰甘油水平低于对照组,高密度脂蛋白胆固醇高于对照组,差异有统计学意义(P均<0.05);观察组治疗后空腹胰岛素、胰岛素抵抗指数低于对照组,胰岛β细胞功能指数高于对照组,差异有统计学意义(P均<0.05);两组不良反应总发生率对比,差异无统计学意义(P>0.05)。结论恩格列净片与格列奇特缓释片联用治疗可使2型糖尿病患者血糖血脂水平得到更为有效的控制,改善患者胰岛β细胞功能,且不会明显增加不良反应。

格列齐特缓释片联合二甲双胍对老年2型糖尿病患者胰岛功能和肾功能的影响

目的:探讨格列齐特缓释片联合二甲双胍对老年2型糖尿病(T2DM)患者胰岛功能和肾功能的影响。方法:选取2022年3月至2023年4月该院收治的68例老年T2DM患者进行前瞻性研究,按照随机数字表法将其分为研究组和对照组各34例。对照组口服盐酸二甲双胍片治疗,研究组在对照组基础上联合格列齐特缓释片治疗。比较两组治疗前后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2hPG)]、胰岛素功能指标[空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)]、血清炎性因子[白三烯B4(LTB4)和趋化因子受体4(CXCR4)]、肾功能指标[胱抑素C(CysC)、血肌酐(SCr)、24 h尿蛋白总量(24UP)]水平,以及不良反应发生率。结果:治疗后,研究组FPG、2hPG、FINS、HOMA-IR、LTB4、SCr、CysC及24hUP水平均低于对照组,血清CXCR4水平高于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:格列齐特缓释片联合二甲双胍治疗老年T2DM患者效果显著,能够降低血糖水平,减轻胰岛素抵抗,缓解机体微炎症状态,保护肾功能,效果优于单用二甲双胍治疗。

达格列净联合二甲双胍治疗2型糖尿病的效果观察

目的探讨对2型糖尿病患者采用达格列净+二甲双胍药物完成治疗后获得临床效果。方法选取2020年10月—2021年10月广宁县人民医院100例2型糖尿病患者,按照随机数字表法分为常规组和研究组,各50例。常规组采用格列齐特缓释片+二甲双胍缓释片治疗,研究组采用达格列净+二甲双胍缓释片治疗。比较两组患者治疗结果。结果研究组治疗总有效率(98.00%)高于常规组(84.00%),差异有统计学意义(χ^(2)=5.983,P<0.05)。治疗后,研究组三酰甘油、低密度脂蛋白、总胆固醇以及体质指数均低于常规组,差异有统计学意义(P<0.05)。治疗后,研究组空腹血糖、糖化血红蛋白、餐后2 h血糖水平均低于常规组,差异有统计学意义(P<0.05)。结论达格列净+二甲双胍缓释片联合应用,可显著提高患者治疗效果,显著改善血脂水平以及体质量,有效降低血糖水平,促进2型糖尿病患者总体预后水平改善。

格列齐特缓释片的制备及体外释放研究

目的 制备格列齐特缓释片,考察其体外释放行为。方法 考察缓释材料羟丙甲纤维素(HPMC)K4M和K100LV不同比例、填充剂(二水磷酸氢钙和糊精)不同用量及不同润湿剂对格列齐特缓释片体外释放度的影响,筛选确定最优处方,并考察其在pH 7.4磷酸盐缓冲液、pH 6.8磷酸盐缓冲液、pH 4.5醋酸盐缓冲液和纯化水4种介质中的释放行为。结果 最优处方中,HPMC K4M和K100LV质量比为1:1,二水磷酸氢钙用量为50%,糊精用量为10%,润湿剂为50%乙醇溶液,制备的格列齐特缓释片在4种介质中的相似因子(f2)均大于70,体外释放符合Higuchi方程。结论 制备的格列齐特缓释片与参比制剂体外释放行为相似。

格列齐特片(Ⅱ)溶出曲线考察与有关物质测定

目的评价山东省内流通的格列齐特片(Ⅱ)的质量。方法抽取国内8家企业生产并在山东省内流通的格列齐特片(Ⅱ)样品58批,按药物溶出曲线测定和相似性比较技术指导原则方法进行溶出曲线考察,并采用相似因子(f2)法比较。按2020年版《中国药典(二部)》格列齐特片(Ⅱ)有关物质测定方法测定制剂中杂质B含量,并建立杂质谱。结果各企业样品溶出曲线与参比制剂比较,f2范围在58.7~80.2之间,相似性良好。各企业样品均有杂质B检出,杂质B含量在0.00006%~0.00176%之间,其中G企业样品检出批数及含量高于其他企业;建立的杂质谱主要存在6种杂质,指认出其中4种分别为对甲苯磺酰脲、对甲苯磺酰胺、杂质B、杂质Ⅰ。结论不同企业间样品质量存在一定差异,主要表现在溶出度和杂质含量方面。山东省内流通的格列齐特片(Ⅱ)药品整体质量良好,为了进一步提高产品的安全性和有效性,建议对其有关物质进行控制。

基础胰岛素治疗初发2型糖尿病的效果观察

目的:探讨基础胰岛素治疗初发2型糖尿病(T2DM)的效果。方法:选取2021年4月—2022年8月云南省昆明市东川区人民医院收治的40例T2DM患者作为研究对象,根据随机数字表法分为对照组和观察组,各20例。对照组给予盐酸二甲双胍缓释片与格列齐特缓释片治疗,观察组在对照组基础上加用甘精胰岛素治疗。比较两组治疗前后空腹血糖(FPG)、餐后2 h血糖(2 hPBG)、空腹血清C肽(CP)、餐后2 hCP、甘油三酯(TG)、总胆固醇(CHO)、低密度脂蛋白胆固醇(LDL-C)、尿微量白蛋白(UAE)水平及低血糖发生情况。结果:治疗7、30 d后,观察组FPG水平低于对照组,差异有统计学意义(P<0.05)。治疗7、30、90 d后,观察组2 hPBG水平低于对照组,餐后2 hCP水平高于对照组,差异有统计学意义(P<0.05)。治疗90 d后,观察组空腹CP水平高于对照组,差异有统计学意义(P<0.05)。治疗90 d后,观察组TG水平低于对照组,差异有统计学意义(P<0.05)。治疗30、90 d后,观察组LDL-C、UAE水平低于对照组,差异有统计学意义(P<0.05)。两组低血糖发生率比较,差异无统计学意义(P>0.05)。结论:基础胰岛素可明显降低T2DM患者的血糖水平,改善血脂指标,降低尿微量白蛋白水平,临床效果显著。

格列齐特缓释片的制备及体外释放度

选用两种黏度的羟丙甲纤维素为骨架材料和粘合剂,采用湿法制粒制备格列齐特缓释片;并与参比制剂比较体外释放行为。结果表明,所得片剂的体外释放符合一级动力学规律,释放曲线经f2(相似因子)判断,与参比制剂相似。

格列齐特缓释片的研制及体外释放度考察

目的;制备格列齐特缓释片并考察其体外释放度。方法采用混合骨架材料制备格列齐特缓释片;参照进口格列齐特缓释片标准,采用紫外分光光度法,以pH7.4磷酸盐缓冲液900ml为溶剂,桨法测定本品释放度,并与参比制剂进行比较。结果所得缓释片体外释放度符合一级动力学规律,释放曲线经相似因子(f2)判断,与参比制剂相似。结论本品处方工艺稳定、重现性好,体外累积释放度符合要求。

HPLC分离测定格列齐特片及其有关物质

目的 :建立新的 HPL C法分离测定格列齐特片及其有关物质。方法 :色谱条件为 :Shim- Pack VP- ODS(5 μm,15 0 mm×4.6 m m i.d.)色谱柱 ;甲醇 - 0 .0 2 m ol/ L 磷酸 (用三乙胺调节 p H至 3.5 ) (70∶ 30 )为流动相 ;检测波长为 2 2 9nm。结果 :在 5 0～ 30 0μg/ m l的浓度范围内线性关系良好 ,r=0 .9999(n=6 ) ;平均回收率为 10 0 .5 % ,RSD为 0 .17% (n=6 ) ;重复进样 RSD为0 .12 % (n=6 ) ;格列齐特及其有关物质得到基线分离。结论 :本法简便、快速、准确 。

高效液相色谱法测定格列齐特缓释片的含量

目的 :建立格列齐特缓释片的含量测定方法 ,以控制该制剂的质量。方法 :采用高效液相色谱法 (HPLC)测定格列齐特缓释片的含量 ,以C18为固定相 ,甲醇 0 .0 2mol·L-1磷酸二氢钠溶液 (6 4∶36 )为流动相 ,检测波长为 2 2 9nm。结果 :格列齐特在 8.0 16～ 12 .0 2 4mg·L-1浓度范围内 ,峰面积与其浓度呈良好的线性关系 ,相关系数r =0 .9992 ,辅料无干扰 ,平均回收率为 99.5 % ,RSD为 0 .7% (n =6 )。结论 :本方法简便、快速、准确 ,可用于格列齐特缓释片的含量测定。

高效液相色谱法测定格列齐特缓释片的含量

目的采用HPLC法测定格列齐特缓释片中格列齐特的含量。方法用Hypersil ODS2（5μm，4．6mm×250mm）色谱柱，甲醇-水（60：40），水相用冰醋酸调至pH3．30为流动相，检测波长228nm。结果格列齐特在0．6～6μg／ml间线性关系良好，相关系数为0．9991．回收率为99．18％，RSD为1．27％。结论本法准确可行，可作为制剂质量控制。