D-最优混料试验设计法优化阿德福韦酯片处方

摘 要 目的：优化阿德福韦酯片处方,并考察其体外溶出度。方法: 以填充剂用量（X1,%）、崩解剂用量（X2,%）和黏合剂用量（X3,%）为影响因素,以脆碎度（Y1,%）、崩解时限（Y2,min）、阿德福韦酯30 min溶出度（Y3,%）为评价指标,采用D 最优混料试验设计法对阿德福韦酯片处方进行优化;采用f2相似因子法比较阿德福韦酯片仿制制剂和参比制剂的体外溶出行为相似性;通过高温、高湿、光照试验初步评价仿制制剂的稳定性。结果: 阿德福韦酯片的最优处方组成为：填充剂一水乳糖用量占片重67.0%、崩解剂交联羧甲基纤维素钠占片重8.0%,黏合剂预胶化淀粉占片重12.0%,制备的片剂脆碎度较低、崩解时限较短、药物溶出度高。阿德福韦酯片仿制制剂和参比制剂在4种溶出介质中的溶出相似因子f2均大于50。影响因素试验结果要求本品应防潮保存。结论: 通过D 最优混料试验设计法优化得到的阿德福韦酯片处方与参比制剂体外溶出一致性良好,制备工艺可行,能够满足制剂大生产的要求。     

黄芩苷分散片的制备及质量控制

目的:制备黄芩苷分散片并建立其质量控制方法。方法:以崩解时间为指标,采用正交设计试验对黄芩苷分散片的处方进行优化,并采用HPLC法测定其含量和溶出度。结果:优化处方为交联聚维酮40%、羧甲基淀粉钠6%和预胶化淀粉2%;按优化处方制备的黄芩苷分散片在3min内完全崩解,15min溶出度达到90%以上。结论:本制备工艺简单、可行;所制分散片崩解迅速、溶出度高。     

正交设计优化依巴斯汀分散片处方

目的优化依巴斯汀分散片处方,研究其制备工艺。方法以片剂的分散均匀性、溶出度和在水中的口感等为指标,采用正交设计综合平衡法优化依巴斯汀分散片处方。结果优化所得处方含有稀释剂预胶化淀粉75mg、乳糖75mg,崩解剂交联羧甲纤维素钠14mg,助溶剂柠檬酸3mg,矫味剂甜菊素2mg。以此处方制备的分散片分散均匀性≤3min,30min的溶出度大于80%,片剂加水分散后口感良好。结论优化所得处方合理稳定,分散片30min时溶出明显优于普通片。     

芪天分散片的成型工艺研究

目的 优选芪天分散片的成型工艺条件.方法 采用单因素及正交设计试验,以多个指标优化芪天分散片的成型工艺处方.结果 以63%微晶纤维素为填充剂、10%羧甲基淀粉钠与交联聚乙烯吡咯烷酮联用为崩解剂、2%羟丙基纤维素为溶胀性辅料、5%聚乙烯吡咯烷酮的50%乙醇溶液为黏合剂,所制得的分散片在1min内完全崩解,5min内溶出度可达85%以上.结论 优选的处方辅料种类及比例适宜、崩解迅速、其体外溶出度明显优于普通片.     

缬沙坦分散片的研制

目的制备缬沙坦分散片并对其相关性能进行考察。方法采用L9(34)正交试验设计法,以综合评分法筛选出最佳处方;采用紫外分光光度法测定产品45min的累积溶出度。结果优化后的处方制得的分散片外观光洁,在1min内完全崩解,20min溶出度可达95%以上,各项指标均符合药典规定。结论优化所得处方合理,制备工艺简单,产品性能良好。     

酮洛芬羟丙基-β-环糊精分散片的处方研究和溶出度考察*

目的:制备酮洛芬羟丙基-β-环糊精包合物(KP-HP-β-CD)分散片并考察体外溶出度.方法:以崩解时间为指标,采用正交设计方法对处方进行筛选和优化,转篮法考察分散片的体外溶出度.结果:分散片优化处方的崩解剂为羧甲基淀粉钠(CMS-Na),用量12%,表面活性剂十二烷基硫酸钠(SLS)用量1%,分散片崩解时间为(112.7±5.0)s.体外溶出参数分别为:T50=3.0 min,Td=5.4 min.结论:该分散片符合中华人民共和国药典2005年版的规定,溶出速度明显快于普通片.     

贝诺酯分散片的制备及质量控制

目的探讨贝诺酯分散片的制备工艺及质量控制方法。方法以崩解时间为指标筛选辅料的种类;采用紫外分光光度法测定贝诺酯分散片在5 min内的累积溶出量,通过正交试验筛选出最优处方。结果优化最佳处方为微晶纤维素42%,羧甲淀粉钠13%,淀粉2%,硬脂酸镁0.5%。结论所制备的贝诺酯分散片具有良好的溶出度,15 min内即可溶出90%,2.5 min内完全崩解,且符合分散片的其他要求。     

三清降糖分散片的处方优化

目的：制备三清降糖分散片并优化其处方工艺。方法：以崩解时限为指标,对填充剂、崩解剂类型进行单因素考察,并通过正交试验优化;高效液相色谱（HPLC）法测定优选处方所制分散片黄芩苷含量和溶出度。结果：优化处方为30%微晶纤维素、20%预胶化淀粉作为填充剂,6%交联聚维酮作为崩解剂,2%微粉硅胶作为润滑剂。按优化处方粉末直接压片制备的三清降糖分散片3 min内分散均匀,15 min溶出度达到90%以上。结论：按优选处方制得的三清降糖分散片,遇水崩解迅速、分散均匀性好,质量可控。     

伐昔洛韦分散片的处方筛选研究

目的:筛选和优化伐昔洛韦分散片的处方。方法:以崩解时限为考察指标,以交联聚乙烯吡咯烷酮(PVPP)浓度及加入方法、粘合剂聚维酮(PVP-K30)浓度、羧甲基淀粉钠(CMS-Na)的用量为因素,采用L9(34)正交试验表设计试验方案,对伐昔洛韦分散片处方进行筛选,并与普通片进行体外溶出度比较。结果:最佳处方为PVPP(内加)4.0%、PVP-K301.0%、CMS-Na5.0%;按优化处方制备的伐昔洛韦分散片在3min内完全崩解,溶出度明显优于普通片。结论:优化处方达到《中国药典》规定要求。     

玄归止痛分散片的处方工艺研究

目的:研制玄归止痛分散片并优化其处方工艺。方法:以崩解时限为指标,对填充剂、崩解剂、黏合剂类型或用量及压片压力进行单因素考察,并通过正交试验优化混合崩解剂、微晶纤维素和微粉硅胶的用量;对优选处方所制分散片进行质量检查,测定其崩解时限、延胡索乙素含量和溶出度;采用相似因子法对本制剂及其滴丸体外溶出的相似度进行评价。结果:优选处方以25%微晶纤维素为填充剂、9%交联聚乙烯吡咯烷酮和9%低取代羟丙基纤维素为混合崩解剂、85%乙醇溶液为黏合剂,微粉硅胶2%,3.0 kg/cm2压力压片;所得分散片崩解时限约为1.22 min,延胡索乙素含量为1.097 mg/g,溶出度10 min时大于80%、15 min时大于90%;以滴丸为参比制剂计算溶出曲线的相似因子为62。结论:所制玄归止痛分散片崩解迅速,且与滴丸的体外溶出行为相似。     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Emerging drugs for epilepsy

Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals.     

盐酸达泊西汀中甲磺酸甲酯、甲磺酸乙酯及甲磺酸异丙酯的顶空毛细管GC-ECD法测定

建立了衍生化顶空毛细管气相色谱-电子捕获检测器(ECD)法测定盐酸达泊西汀中的甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS).应用碘化钠衍生技术,使用PW-5毛细管柱,载气为氮气,ECD检测,程序升温.MMS、EMS和IMS分别在0.03～0.30、0.05～0.50和0.05～0.50 μg/ml浓度范围内线性关系良好,平均回收率分别为63.5％、100.3％和96.2％,最低检测限分别为0.30、0.50和0.50 ng/ml.     

血管内皮生长因子的异常与子(癎)前期发病的关系

目的:研究血浆可溶性细胞间黏附分子-1(sICAM-1)浓度和胎盘组织血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)及其血管内皮生长因子受体1(VEGFR1,Flt-1)、可溶性血管内皮生长因子受体1(sVEGFR1,sFlt-1)mRNA的表达与子前期的关系.方法:采用酶联免疫吸附测定法(ELISA)检测45例子前期患者和45例健康产妇血清sICAM-1的浓度,逆转录-聚合酶链反应(RT-PCR)方法检测胎盘组织中VEGF、PLGF、Flt-1、sFlt-1 mRNA的表达.结果:(1)子前期组sICAM-1水平为(218.45±29.93) μg/L,显著高于对照组的(168.84±19.39) μg/L(P < 0.01).(2)子前期患者胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量显著高于对照组(均P < 0.01).(3)血清sICAM-1浓度与胎盘组织中sFlt-1mRNA的相对表达量呈正相关(r = 0.90,P < 0.01).结论:子前期患者血清sICAM-1浓度升高,其胎盘组织VEGF、PLGF、Flt-1、sFlt-1 mRNA的相对表达量也升高.胎盘组织sFlt-1mRNA的高表达与子前期内皮损伤等有密切关系.     

Antiparasitic protozoan vaccines

Parasitic infections caused by pathogenic protozoa affect over 1 billion people worldwide and impose a substantial health and economic burden, particularly on inter-tropical less-developed countries where they are more prevalent. Despite encouraging progress in vaccine development, chemotherapy remains the single most effective, efficient and inexpensive means to control most parasitic infections [1]. However, day to day parasites are becoming increasingly resistant to drugs currently in use, such as Plasmodium towards chloroquine, lending to the start of a promising future for vaccines. Patent applications regarding vaccines for the prevention, control and diagnosis of parasitic protozoan infections are reviewed for the period December 1996 - October 2000. However, vaccines for some of the protozoan infections do not appear in the literature in the period reviewed; only, vaccines against malaria, leishmaniasis, trypanosomiasis, cryptosporidiosis, pneumocystosis, eimeriosis, toxoplasmosis and neosporosis, as well as Babesia microti infections have been found.     

Binding affinity in drug design: experimental and computational techniques

ABSTRACT

Introduction: In pharmaceutical design where future drugs are developed by targeting a specific chosen protein, the evaluation of ligand affinity is crucial. For this very purpose are a multitude of diverse methods which are continuously being improved, which, in turn, makes it difficult to choose which techniques to use in practice.

Areas covered: In this review, the authors discuss both experimental and computational approaches for affinity evaluation. Basic principles, general limitations and advantages, as well as main areas of application in drug discovery, are overviewed for some of the most popular ligand binding assays. The authors further provide a guide to affinity predictions, collectively covering several techniques that are used in the first stages of rational drug design.

Expert opinion: All affinity estimation methods have limitations and advantages that partially overlap and complement one another. Some of the suggested best practices include cross-verification of data using at least two different techniques and careful data interpretation.