Structure based release kinetics analysis of doxazosin mesylate sustained-release tablets using micro-computed tomography

The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage forms.Here,the 3D structures of doxazosin mesylate sustained-release tablets were parallelly assessed by micro-computed tomography(micro-CT).There were no significant differences observed in the release profiles between the RLD and the generic formulation in the conventional dissolution,but the generic preparation released slightly faster in media with ethanol during an alcohol-induced dose-dumping test.With their 3D structures obtained via micro-CT determination,the unique release behaviors of both RLD and the generic were investigated to reveal the effects of internal fine structure on the release kinetics.The structural parameters for both preparations were similar in conventional dissolution test,while the dissolutions in ethanol media showed some distinctions between RLD and generic preparations due to their static and dynamic structures.Furthermore,the findings revealed that the presence of ethanol accelerated dissolution and induced changes in internal structure of both RLD and generic preparations.Moreover,structure parameters like volume and area of outer contour,remaining solid volume and cavity volumewere not equivalent between the two formulations in 40%ethanol.In conclusion,the structure data obtained from this study provided valuable insights into the diverse release behaviors observed in various modified-release formulations in drug development and quality control.

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.

The impact of Hypoglycemic Ziyabiti Tablets (HZT) on diabetes mellitus rats and its activity in cultured rat liver cells

Objective Hypoglycemic Ziyabiti Tablets(HZT)is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and its activity in cultured liver cells to investigate the relative mechanisms.Methods 10 days high-fat diet fed rats were intraperitoneally injected with alloxan(ALX)at next two subsequent days to induce diabetes mellitus(DM).Then were divided into 5 groups:saline,positive DM control and DM groups treated with different doses of HZT.Fasting blood glucose(FBG),total cholesterol(TC),total triglycerides(TG),high-density lipoprotein(HDL-C),fasting insulin(FI),insulin secretion(IS)and insulin sensitivity index(ISI)were measured.The IC_(50) of HZT in L-02 cells was determined by MTT assay,in intact and in paracetamol-induced liver injury(Par),on lactate dehydrogenase(LDH)activity and on glucose consumption.Results HZT decreased FBG and TC(P <0.05),increased IS(P <0.05)and at 440 mg·kg^(-1)·d^(-1) increased FI(P < 0.01).In vitro,HZT at 0.1,0.2,and 0.4 mg/mL decreased LDH activity and promoted glucose consumption.Conclusion The hypoglycemic mechanism of HZT is possibly related to increased insulin secretion from the pancreas and increased utilization of glucose by the liver.

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.

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.

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.

桑叶苦荞压片糖果配方优化及其降糖活性

为优化桑叶苦荞压片糖果配方,探究其体外降糖能力,以桑叶和苦荞的超微粉及提取物为主要原料,采用粉末直接压片法,选取感官评价、脆碎度为评价指标,通过“棋盘法”优化试验确定最佳配方,并对其体外降糖能力进行评价。结果表明,桑叶苦荞压片糖果以超微粉为原料,最佳配方即产品A配方为桑叶超微粉5%、苦荞超微粉5%,山楂水提物2%,山梨糖醇50%,微晶纤维素37%,硬脂酸镁1%;以桑叶和苦荞的提取物为原料,最佳配方即产品B和产品C,配方为桑叶水/醇提物20%、苦荞水提物20%、山楂水提物3%、山梨糖醇34%、微晶纤维素22%、硬脂酸镁1%,产品A、产品B和产品C对α-葡萄糖苷酶的IC_(50)值分别为(14.68±0.04)、(3.48±0.04)、(5.48±0.03)mg/mL,对α-淀粉酶的IC_(50)值分别为(17.42±0.03)、(11.54±0.02)、(10.55±0.03)mg/mL,具有较强的体外降糖能力。

彩麦麸皮戊聚糖泡腾片的制备及其降血糖活性评价

研究彩麦麸皮戊聚糖降糖效果、泡腾片制备配方及其降低人体餐后血糖的效果。结果表明:当彩麦麸皮戊聚糖质量浓度为10 mg/mL时,对α-葡萄糖苷酶的抑制率为54.57%,对α-淀粉酶的抑制率为56.57%,IC_(50)分别为9.16、8.05 mg/mL;以泡腾片质量为基准,当彩麦麸皮戊聚糖添加量为20%、泡腾片崩解剂添加量为55%、碱酸质量比为1∶1.1时,泡腾片综合评分最高,为0.88;制备的泡腾片平均片重约为501 mg,每片戊聚糖含量约为56 mg,服用后餐后血糖高峰值降低率人均高达50.4%,最高达到69.6%,降低餐后血糖效果明显。

金芪降糖片对胰岛素抵抗和高血压的影响

目的:观察中药金芪降糖片对果糖诱导的胰岛素抵抗高血压大鼠胰岛素敏感性和血压的影响。方法:Wistar大鼠40只,30只建立果糖诱导的胰岛素抵抗高血压大鼠模型,设对照组(C组)10只以普通水灌胃。果糖饮水加罗格列酮治疗组(R组)10只,以罗格列酮溶液灌胃;果糖饮水加金芪降糖片治疗组(J组)10只,以金芪降糖片溶液灌胃;果糖饮水加果糖灌胃组(F组)10只,以10%果糖的普通水灌胃,共灌胃6周,实验前后测定大鼠尾动脉压,结束后取血测定血清空腹血糖(FBG)、空腹血清胰岛素浓度(FINS)、血清抵抗素浓度(resistin)。计算胰岛素敏感性指数(ISI)。结果:实验结束后J组、R组和C组ISI均明显高于F组,同时血压明显低于F组;抵抗素水平J组、R组明显低于F组。结论:中药金芪降糖片可改善胰岛素抵抗个体胰岛素敏感性,并降低血压。

金芪降糖片的研究概述

金芪降糖片是依据传统古方、以现代实验药理学方法进行优化组合、经临床确证为安全有效的新型降糖药。研究证明本药能改善机体糖代谢和脂质代谢,恢复对胰岛素的敏感性,增强免疫功能。用于Ⅱ型糖尿病中属于中医诊断为气阴两虚并有内热证候的消渴病患者,效果明显。临床研究446例(其中对照组106例)表明,其降血糖总有效率为75%,显效率为38%。金芪降糖片对兼有高血脂的糖尿病患者也能起降脂作用。

百草降糖片降血糖作用机制研究

目的 探讨百草降糖片的降血糖作用机制。方法 观察了百草降糖片对正常小鼠血糖、血清胰岛素、胰高血糖素、肝糖原、肌糖原的影响 ,并且观察了百草降糖片对糖尿病大鼠的血清胰岛素、C肽、超氧化物歧化酶( SOD)、过氧化脂质 ( L PO)的影响。结果 百草降糖片在降糖的同时能刺激胰岛素的分泌 ,降低胰高血糖素的含量 ,而且能增加肝糖原、肌糖原的含量 ;对四氧嘧啶糖尿病大鼠在降糖的同时也能增加胰岛素、C肽水平 ,而且能显著增加血清 SOD的活性 ,降低 L PO含量。结论 百草降糖片的降血糖作用可能是既通过影响糖代谢 ,又通过改善胰岛功能 。

KPCA-聚类分析法和用便携式拉曼仪快速鉴别降糖药

对不同种类的降糖药片进行拉曼光谱的核主成分分析(KPCA)-聚类分析,实现快速、简便的鉴别。KPCA可以有效地避免主成分分析(PCA)只能处理线性问题和降维效果不明显的弊端。它通过一个非线性变换,首先将原变量空间映射到高维特征空间,然后在这个高维特征空间中进行线性主成分分析。采集得到的药片拉曼光谱的KPCA-聚类分析结果表明,采用KPCA提取特征变量的聚类结果比采用PCA提取特征变量后进行聚类分析的效果好,并且未经刮除表面包膜的降糖药片识别准确率为96.5%,经过刮除表面包膜处理的降糖药片的识别准确率为100%。便携式拉曼光谱仪结合该方法以其检测速度快、准确率高、使用简便、无样品前处理等显著优势,为药品的快速检验技术提供一种新的有效的鉴别手段。

HPLC-ELSD测定胡芦巴降糖缓释片中薯蓣皂苷元的含量

目的:建立HPLC-ELSD测定胡芦巴降糖缓释片含量的方法。方法:高效液相色谱法测定含量,色谱柱:岛津VP-ODS(4.6mm×150mm,5μm),流动相:甲醇-水(84∶16),检测波长:203nm,流量:1.0mL.min-1,柱温:40℃,漂移管温度:85℃,气流体积流量:2.5L·min-1。结果:该方法下薯蓣皂苷元标准曲线为Y=812991.42X+1252792.92,r=0.9996(n=5),线性范围为0.842～8.42μg,平均回收率为98.53%(n=6)。结论:该方法准确可靠、重现性好,可用于胡芦巴降糖缓释片中著蓣皂苷元的含量测定。

降糖孜亚比提片在正常和糖尿病小鼠中的抗高血糖活性(英文)

目的:研究降糖孜亚比提片的抗高血糖活性。方法:采用正常小鼠、四氧嘧啶和肾上腺素导致的高血糖小鼠对降糖孜亚比提片的降糖作用进行研究。结果:降糖孜亚比提片对正常小鼠血糖无影响;能够提高小鼠的糖耐量;对四氧嘧啶引起的高血糖小鼠的血糖有明显的抑制作用;还能使肾上腺素所致的高血糖小鼠血糖降低;增加肝糖原的含量,减少肝糖原的输出。结论:降糖孜亚比提片具有明显的降血糖作用。

基于拉曼光谱法的降糖类药物的判别方法比较

采用了四种聚类方法对降糖类药物拉曼光谱进行了快速、无损判别。采集九种降糖类药品共48个样品的拉曼光谱,经截波、基线校正、平滑、矢量归一化等预处理后,分别采用K-均值、系统聚类法、自组织图(SOM)及PCA-SOM四种不同聚类方法做聚类判别。结果表明,自组织图与K-均值、系统聚类法相比,聚类结果较好,并且SOM结合PCA后的PCA-SOM结果最优。为降糖类药品的快速判别从聚类的角度提供了一种新的方法。

金芪降糖片对实验动物糖代谢的影响

金芪降糖片是一种新型的抗糖尿病中药复方。它能降低正常小鼠、四氧嘧啶小鼠、大鼠以及自发性肥胖性糖尿病小鼠的血糖水平，并能改善四氧嘧啶小鼠糖耐量，降低血乳酸，减少皮肤糖含量，促进肝糖原的合成。