吡格列酮二甲双胍片治疗2型糖尿病的多中心随机双盲平行对照临床试验

目的 以盐酸二甲双胍和盐酸吡格列酮(均降糖药)为对照,评价吡格列酮二甲双胍片治疗2型糖尿病的疗效和安全性.方法 用多中心随机双盲双模拟阳性平行对照的试验设计,观察240例2型糖尿病病人,分为吡格列酮二甲双胍片组(试验组)和盐酸二甲双胍、盐酸吡格列酮组(对照组).结果 用药16周后,与基础值相比,试验组空腹血糖(FBG)、餐后2 h血糖(P2hBG)、糖化血红蛋白(HbAlC)分别下降(1.92±1.77)mmol·L~(-1),(2.49±3.13)mmol·L~(-1),(1.27±1.45)%;对照组,FBG、PBG、HbA1c分别下降(2.24±2.11)mmol·L~(-1),(2.89±3.71)mmol·L~(-1),(1.49±1.52)%,2组下降各指标治疗前后比较均有显著性差异;但2组间比较无显著性差异.2组不良反应发生率比较无统计学差异(10% vs 12%).结论 吡格列酮二甲双胍片是治疗2型糖尿病有效和安全的药物.     

二甲双胍和吡格列酮治疗2型糖尿病伴高脂血症的疗效分析

目的 :探讨盐酸吡格列酮和盐酸二甲双胍对2型糖尿病患者高脂血症的疗效。方法 :采取平行双盲随机对照法 ,两组病例随机分为二甲双胍治疗组和盐酸吡格列酮治疗组。治疗12周为1个疗程。治疗前后分别检测血清胆固醇 (TC)、甘油三脂 (TG)、低密度脂蛋白胆固醇 (LDL -C)、高密度脂蛋白胆固醇 (HDL -C)、空腹血糖 (FBG)、餐后2小时血糖 (2hPG)、肝功能、肾功能。结果 :两种药均有降低甘油三脂、胆固醇、低密度脂蛋白胆固醇 ,升高高密度脂蛋白胆固醇作用。二甲双胍降低胆固醇的幅度优于吡格列酮 ,但两种药对甘油三脂、高密度脂蛋白胆固醇的影响幅度差异无显著性。结论 :盐酸吡格列酮和盐酸二甲双胍两种药对2型糖尿病的高脂血症疗效相当     

吡格列酮/二甲双胍缓释片的处方筛选及工艺研究

目的确定吡格列酮/二甲双胍缓释片处方及制备工艺。方法分别以释放度及溶出度为指标对二甲双胍缓释骨架层及吡格列酮速释层进行处方和工艺研究,并对吡格列酮/二甲双胍缓释片的释放度进行考察。结果吡格列酮/二甲双胍缓释片缓释层体外释放行为与模型药物Glucophage XR(格华止)相似,速释层吡格列酮与模型药物Actos(艾可拓)体外溶出行为不相似,但30 min累计溶出药物总量相似。结论所制备的吡格列酮/二甲双胍缓释片处方组成合理,工艺可行。     

复方盐酸吡格列酮/盐酸二甲双胍控释片的制备及体外释放考察

目的：盐酸吡格列酮（PG）和盐酸二甲双胍（MH）可联用治疗2型糖尿病,两者通过机理上的互补可增强对患者血糖的调控。本文通过将两者制成复方控释片达到联合用药,延长并控制药物释放的目的,并考察其体外释放特性。方法：以聚乙烯吡咯烷酮（PVPK30）、乳糖、MH作为片芯,通过湿法制粒压片,使用含醋酸纤维素、聚乙二醇（PEG400）、苯甲酸甲酯的包衣液进行包衣形成半透膜,并在片两面通过激光打孔机各打一小孔,进一步在控释片表面包PG的速释层,形成复方控释片。对片芯处方和控释层包衣液处方进行筛选,控制包衣膜厚度和释药孔径。结果：MH可达到24 h零级释放,PG快速释放。PEG400和苯甲酸甲酯用量,包衣膜厚度对MH释放有显著影响。结论：通过正交设计和单因素考察,可得到最优处方的复方控释制剂,零级释药和快速释药,并达到联合用药的目的。     

盐酸吡格列酮缓释片处方筛选及工艺研究

目的:对盐酸吡格列酮缓释片进行处方筛选及工艺研究。方法:通过测定不同时间吡格列酮在pH6.8磷酸盐缓冲液中的累积释药率,对缓释骨架材料、填充剂、黏合剂的种类或规格、用量及工艺等进行考察,确立片芯处方及制备工艺。结果:片芯处方以羟丙基甲基纤维素(HPMC)(K15M)为骨架材料,微晶纤维素为填充剂,2%HPMC(E5)的70%乙醇溶液为黏合剂;制备工艺采用薄膜包衣法,以欧巴代的70%乙醇溶液作为薄膜包衣材料;所制3批样品12h的累积释药率均在90%以上。结论:本制剂工艺简单,符合缓释制剂要求。     

二甲双胍缓释片联合吡格列酮治疗新诊断2型糖尿病的观察

目的观察二甲双胍缓释片联合吡格列酮治疗新诊断2型糖尿病的有效性和安全性。方法选择在集仕港中心卫生院就诊的新诊断2型糖尿病患者48例,根据血糖情况分为甲、乙两组,甲组患者空腹血糖为7.0～11.1mmol·L^-1（26例）,给以二甲双胍缓释片1.5/天,睡前顿服,吡格列酮15mg/天,早晨顿服。乙组患者空腹血糖≥11.1mmol·L^-1（22例）,并查尿酮体阴性,给以预混重组人胰岛素（诺和灵30R）,皮下注射,1日2次,二甲双胍缓释片1日1.5g,睡前顿服。两组患者均控制饮食及运动锻炼,观察用药前后血糖、血脂、糖化血红蛋白、体重指数等变化。结果两组患者在治疗12周后血糖、糖化血红蛋白均有明显下降,差异具有显著意义（P〈0.05）,但两组组间差异无显著意义（P〉0.05）,甲组无严重不良反应发生。结论二甲双胍缓释片联合吡格列酮治疗新诊断2型糖尿病,具有良好的疗效和安全性,可作为一线用药。     

盐酸二甲双胍片与盐酸吡格列酮片联用对2型糖尿病患者降糖作用的临床疗效评价

目的:评价盐酸二甲双胍片与盐酸吡格列酮片联用对2型糖尿病患者降糖作用的临床疗效。方法:选取医院内分泌科2014年3月—2015年3月间收治的2型糖尿病患者112例,按随机数字表法将患者分为观察组和对照组,每组56例;观察组患者均给予盐酸二甲双胍片与盐酸吡格列酮片联用治疗,对照组患者则给予单用盐酸二甲双胍片治疗,比较两组患者治疗前后的血糖指标如空腹血糖值(FPG)、餐后2 h血糖值(P 2 h BG)、糖化血红蛋白值(Hb Alc)值和胰岛素指标如空腹胰岛素值(FINS)、餐后2 h胰岛素(P 2 h INS)值,以及不良反应的发生情况。结果:治疗前两组患者的血糖值和胰岛素指标值经比较其差异无统计学意义(P>0.05);治疗后两组患者的血糖值和胰岛素指标值较治疗前明显下降(P<0.05);观察组患者治疗后的血糖值和胰岛素指标明显优于对照组(P<0.05),其不良反应的发生率为12.50%明显低于对照组为14.29%(P<0.05)。结论:采用盐酸二甲双胍片与盐酸吡格列酮片联用治疗2型糖尿病患者的临床疗效优于单用盐酸二甲双胍片的疗效,可明显改善患者的血糖值和胰岛素指标值,而且不良反应的发生率较低。     

盐酸吡格列酮联合二甲双胍治疗初诊2型糖尿病25例

目的观察盐酸吡格列酮联合二甲双胍缓释片治疗新诊断2型糖尿病的疗效和安全性。方法选择新诊断2型糖尿病患者46例,根据血糖情况分为甲、乙两组。甲组25例空腹血糖为7．0-11．1mmol／L,给予盐酸吡格列酮15mg／d,早晨顿服,二甲双胍缓释片1．5g／d,睡前顿服。乙组21例空腹血糖不低于11．1mmol／L,尿酮体阴性,给予预混重组人胰岛素制剂（优泌林30R）和二甲双胍缓释片1．5g／d,睡前顿服。两组患者均控制饮食及加强运动锻炼,观察用药前后血糖、血脂、糖化血红蛋白、体重指数等的变化。结果两组患者在治疗12周后血糖、糖化血红蛋白均明显下降,差异具有显著意义（P〈0．05）,但组间差异无显著意义（P〉0．05）。甲组无严重不良反应发生。结论盐酸吡格列酮联合二甲双胍缓释片具有良好的疗效和安全性,可作为新诊断2型糖尿病的一线用药。     

复方盐酸吡格列酮二甲双胍缓释片中盐酸吡格列酮溶出度的测定

目的 开发简单、快速、灵敏度高的复方盐酸吡格列酮/盐酸二甲双胍缓释片中盐酸吡格列酮溶出度的测定方法.方法使用HPLC法,以甲醇∶0.025 mol·L-1乙酸铵水溶液(65:35)为流动相;流速1.0 ml·min-1;检测波长229 nm.结果盐酸吡格列酮在0.5～20.2 mg·L-1范围内线性关系良好(r=0.9...     

二甲双胍缓释片联合吡格列酮治疗2型糖尿病的临床效果

目的 观察二甲双胍缓释片联合吡格列酮治疗2型糖尿病的临床效果。方法 采用电脑随机数字表法将2018年3月—2020年3月福建省厦门市第五医院收治的2型糖尿病患者80例分为联合用药组(n=40)、吡格列酮组(n=40),吡格列酮组患者给予吡格列酮治疗,联合用药组患者在吡格列酮组基础上加用二甲双胍缓释片治疗,2组均连续治疗3个月。比较2组患者临床疗效,治疗前后血糖[空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA_1c)]水平、血脂[三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)及低密度脂蛋白(LDL-C)]水平、肝肾功能[天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、尿素氮(BUN)及肌酐(Cr)]水平、血清炎性因子[超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)及白介素-6(IL-6)]水平与不良反应。结果 联合用药组患者治疗总有效率为95.00%,高于吡格列酮组的77.50%(χ²=5.165,P=0.023);治疗3个月后,联合用药组FBG、2 hPG、HbA_1c...     

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-I was affected by dissolution media with different pH, but not for F-II. Hixson–Crowell model 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 of AUC_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.     

Preparation and in vitro/in vivo evaluation of sustained-release venlafaxine hydrochloride pellets

The objective of this study was to prepare different venlafaxine hydrochloride sustained-release products and to elucidate the influence of composition of the coating film on the in vitro drug release profiles and in vivo pharmacokinetics. Pellets were prepared by a standardized process of extrusion/spheronization. A selected fraction size (0.8-1.0 mm diameter) of pellets of each formulation was coated with Eudragit NE30D or ethylcellulose (10 cps). Many efforts have been made to tailor drug release rate by choosing different coating materials, different percent of pore forming components and coating weight variation to achieve a desired sustained-release effect. The dissolution studies were performed and data were analyzed in terms of cumulative release as a function of time. The influence on the release of venlafaxine from sustained-release capsules was observed in dissolution media of different pH and gradient pH. Scanning electron microscope (SEM) micrographs revealed morphological changes of the pellet coating surface which were related to in vitro drug release profiles. The relative bioavailability for Formulation 1 and Formulation 2 was evaluated in six healthy beagle dogs after oral administration in a fast state using sustained-release capsules (Effexor XR) as a reference. The results suggested that Formulation 1 and Formulation 2 both had better bioavailability compared with Effexor XR. It could be found that there existed quite difference in the in vivo release and oral absorption performances, despite the similar in vitro drug release behavior for the two formulations. It might be attributable to complex in vivo environment and then variation in the release behavior. Thus differences in the film micro-structure and surface roughness caused by aqueous dispersion and organic solvent coating techniques strongly influence the in vivo release and oral absorption performances.     

盐酸帕罗西汀肠溶缓释片的制备及体外释放研究

目的制备盐酸帕罗西汀肠溶缓释片,并对其体外释放度进行考察。方法采用HPMC K100LV和HPMC K4M作为骨架材料,以水乳糖为填充剂制备盐酸帕罗西汀缓释片芯,再使用Eudragit L30D-55包肠溶衣,制成盐酸帕罗西汀肠溶缓释片,并采用f_2相似因子法评价自制制剂和参比制剂在释放介质中的体外释放行为。结果体外释放度实验显示,自制制剂和参比制剂的f_2相似因子值大于50。结论制备的盐酸帕罗西汀肠溶缓释片的释药行为与参比制剂的体外释放行为相似。     

谷维素骨架型缓释片的研制与质量评价

目的制备谷维素骨架型缓释片,优化其制备工艺及处方,并对其进行质量评价。方法采用亲水性高分子材料HPMC为骨架,湿法制备谷维素缓释片,并以药物体外累计释放率为指标,结合正交试验优选制剂处方。结果最终优选处方为骨架材料为15%HPMC K15M,填充剂淀粉和乳糖比例为2:1,致孔剂为5%PVP。体外释放度试验表明,与已上市片剂比较,缓释效果明显,体外释放拟合Higuchi方程最佳。结论所制备的缓释片缓释效果显著,制备工艺简单合理,为其新剂型的研制提供了一定的理论和试验基础。     

Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets.

In this study, metformin hydrochloride (MH) sustained-release pellets were successfully prepared by centrifugal granulation. Seed cores preparation, drug layering, talc modification and coating of polymeric suspensions were carried out in a centrifugal granulator. Talc modification was performed before coating in order to overcome the high water solubility of metformin. The influence of surface modification by talc, the effects of Eudragit types and ratios, as well as the correlation between in vitro release and in vivo absorption were investigated in detail. Experimental results indicated that talc modification made a decisive contribution to controlling the drug release by avoiding drug dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate buffer were employed to determine the in vitro release behaviors of the above metformin hydrochloride pellets. The relative bioavailability of the sustained-release pellets was studied in 12 healthy volunteers after oral administration in a fast state using a commercially available immediate release tablet (Glucophage) as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3), the pellets acquired perfect sustained-release properties and good relative bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3 coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%, respectively. Combined use of two Eudragit polymers with different features as coating materials produced the desired results. Restricted delivery of metformin hydrochloride to the small intestine from differently coated pellets resulted in increased relative bioavailability and a sustained release effect. The adoption of several different pH dissolution media established a better relationship between the in vitro release and in vivo absorption of the sustained-release pellets.     

灯盏花素缓释片的制备及体外释放度研究

目的以羟丙甲基纤维素为骨架材料制得灯盏花素缓释片,并对释药机制进行探讨。方法进行体外释放度试验,研究体外释放度测定方法,以及辅料和加速稳定性试验对释放度的影响。结果制得的灯盏花素缓释片体外释放度测定结果符合缓释片质量标准中的释放度标准要求。体外释放符合一级释药动力学规律。结论制备灯盏花素缓释片缓释效果明显．方法简单,适于工业化生产。     

丁螺环酮缓释片的制备及其体外释放度的研究*

目的：研制丁螺环酮缓释片的最佳处方并考察其释放度。方法：以丁螺环酮为模型药物，新型载体材料聚已内酯（PCL）和羟丙基甲基纤维素（HPMC）为骨架材料，湿法制粒压制丁螺环酮缓释片，测定药物的体外释放度，以拟合方程的相关系数r，T25，T50，Td和T80等质量评价指标来进行处方筛选。结果：根据初步筛选的最佳处方制备的缓释片释放曲线符合Higuchi方程，24h释药超过90％。结论：以PCL和HPMC为骨架材料，能制备出释药24h的丁螺环酮缓释片。     

烟酸缓释骨架片的制备及体外释放度考察

目的 :制备烟酸缓释骨架片并考察其体外释放度。方法 :以国外上市 Niaspan R○ 作为对照 ,考察了 4种型号的羟丙基甲基纤维素 (HPMC)对释放性能的影响 ,并比较了缓释片在水、0 .1mol/ L 盐酸及 p H6 .8磷酸盐缓冲液三种介质中的释放度。结果 :用 Higuchi方程拟合发现 ,自制片和对照片均具有典型的缓释性能 ,而且自制片和对照片的释放度没有差别。结论 :自制的烟酸缓释骨架片工艺简单易行 ,释放度亦符合要求。     

萘哌地尔亲水凝胶型缓释片的研制

目的释放度测定方法的建立与萘哌地尔缓释片的研制。方法以0．5％十二烷基硫酸钠为释药介质,释放度为处方筛选指标,采用羟丙甲纤维素作为亲水凝胶型缓释骨架制备萘哌地尔缓释片。结果萘哌地尔从本骨架片中的释药曲线符合零级动力学模型。结论该文研制的萘哌地尔缓释片处方合理,制备方法简单可行,值得进一步研究并发。     

阿莫西林缓释片的制备及体外释放度的研究

目的 研制阿莫西林缓释片，并对其体外释放度进行了考察。方法 以聚乙二醇6000为固体分散体载体，先将阿莫西林制备成固体分散体，增加阿莫西林在水中的溶出度，再以羟丙甲基纤维素为骨架材料，以水为牯合剂，采用湿法制粒压片，制备阿莫西林缓释片，并进行体外释放度试验。结果 该片在1、2、3、6和8h体外释放度控制在30％～45％、45％～65％、60％～80％、75％～95％和90％以上，药物的体外释放模式符合Highuchi方程。结论 研制缓释片的缓释效果良好。