Determination of indometacin in Compound indometacin suppositories by HPLC

目的 采用HPLC法测定复方吲哚美辛栓中吲哚美辛的含量.方法 采用C18色谱柱,流动相为0.05 mol·L-1乙酸-乙腈(50∶50),测定波长260 nm.结果 吲哚美辛25.59～307.13 mg·L-1与峰面积的线性关系良好(r=0.9999),回收率为98.9％(RSD=2.0％,n=6).结论 所用方法准确、可靠,可用于复方吲哚美栓的质量控制.     

吲哚美辛脂质体滴眼液在家兔眼内的药动学

目的:研究吲哚美辛脂质体滴眼液在家兔眼内的药动学过程,为临床应用提供依据和参考.方法:以市售吲哚美辛滴眼液为参比制剂,采用高效液相色谱法(HPLC)测定两种制剂在用药后不同时间家兔房水中的药物浓度,按单剂量方案进行研究并计算药动学参数.结果:两药在家兔眼内均为一室模型,受试药物主要药动学参数为:Tmax=0.204 5 h;Cmax=1.518 7 mg·L-1:AUC=1.981 7 mg·L-1·h.参比药物为:Cmax=0.388 1 mg·L-1,Tmax=0.798 1 h,AUC=0.858 5 mg·L-1·h.结论:与吲哚美辛滴眼液相比吲哚美辛脂质体滴眼液眼内生物利用度提高2.3倍.     

高效液相色谱法测定保留灌肠液中3成分的含量

目的:建立同时测定灌肠液中呋喃唑酮、甲氧苄啶和醋酸泼尼松3种成分含量的方法.方法:流动相:甲醇-水(用醋酸和氨水调至pH 6.6)(60:40);流速:1 mL·min-1;检测波长:231 nm.结果:呋喃唑酮在10～50mg·L-1,甲氧苄啶在10～50 mg·L-1,醋酸泼尼松在2～10mg·L-1范围内线性关系良好,回收率试验结果满意,重复性好.结论:本法简便、准确,可以用于制剂质量控制.     

高效液相色谱法同时测定人血浆中阿西美辛及其代谢物吲哚美辛的浓度

目的:建立高效液相色谱法测定人血浆中阿西美辛浓度的分析方法.方法:以酮洛芬为内标,采用Waters 510型高效液相色谱仪,Discovery C18(150 mm×4.6 mm,5 μm)为分析柱,采用L9(33)法优化的流动相为:甲醇-0.02 mol·L-1醋酸铵溶液(65∶35,V/V),用冰醋酸调至pH5.80,流速为1.0mL·min-1,紫外检测波长250 nm.结果:色谱峰分离良好,无干扰.阿西美辛和吲哚美辛线性方程分别为:Y1=0.4652C-0.00178,r=0.9997和Y2=0.5491C 0.0065,r=0.9999,线性范围分别为:0.069～4.419 mg·L-1和0.0349～2.235 mg·L-1,最低检测浓度分别为:0.069 mg·L-1和0.034 mg·L-1.日内、日间误差分别小于7%和10%,平均回收率大于95%.结论:本方法是一种可靠、快速、灵敏的检测方法,可用于人体血药浓度监测及药动学的研究.     

HPLC测定复方吲哚美辛栓中的吲哚美辛

目的采用HPLC法测定复方吲哚美辛栓中吲哚美辛的含量。方法采用C18色谱柱,流动相为0.05 mol·L-1乙酸-乙腈(50∶50),测定波长260 nm。结果吲哚美辛25.59～307.13 mg·L-1与峰面积的线性关系良好(r=0.9999),回收率为98.9%(RSD=2.0%,n=6)。结论所用方法准确、可靠,可用于复方吲哚美栓的质量控制。     

RP-HPLC法测定吲哚美辛5-氟尿嘧啶甲酯原料药含量及有关物质

目的用RP-HPLC法测定吲哚美辛5-氟尿嘧啶甲酯原料药含量和有关物质。方法色谱柱:DiamonsilTMC18(250 mm×4.6 mm,5μm),流动相:甲醇-0.025 mol.L-1醋酸铵(体积比为65∶35)(用冰醋酸调节pH至3.5),流速:1 mL.min-1,检测波长:260 nm,柱温:40℃。结果在选定的色谱条件下,有关物质与主药分离良好,最低检测限2.0μg.L-1,吲哚美辛5-氟尿嘧啶甲酯的质量浓度在5.0~50.0 mg.L-1内线性关系良好(r=0.999 9),平均回收率99.7%,RSD=1.0%。结论该法适用于吲哚美辛5-氟尿嘧啶甲酯原料药含量和有关物质检查。     

吲哚美辛胶囊含量测定方法的改进

目的:依据《中国药典》2005年版二部测定不同生产厂家的吲哚美辛胶囊含量,测定的含量值偏低且重现性差,分析吲哚美辛理化性质认为原方法从吲哚美辛胶囊内容物中提取吲哚美辛不完全。为此,进行了方法改进。方法:由药典方法"振摇提取"改进为"研磨内容物,超声提取1h";对两种测定方法进行了统计分析,表明方法间存在系统误差;对改进方法进行了方法学考察,结果吲哚美辛进样量在0.20014μg～4.0028μg之间线形关系良好,回归方程为y=1379.1x+3.2886,r=0.9997(n=6)。结论:采用改进方法测定吲哚美辛胶囊含量,具有良好精密度和重现性。     

高效液相色谱法测定吲哚美辛滴眼液含量及有关物质

目的:建立测定吲哚美辛滴眼液中吲哚美辛及其有关物质的方法。方法:采用Hypersil ODS色谱柱(4.6mm×250mm,5μm);流动相:0.1mol.L-1冰醋酸-乙腈(40?60,v/v),检测波长:228nm;柱温:30℃;流速:1.0mL.min-1。结果:制剂中其他成分不干扰测定。吲哚美辛与多种降解产物分离良好。吲哚美辛在24.6~393.6mg.L-1(r=0.999 8,n=6)范围内呈良好的线性关系;模拟回收率平均为100.4%,日内RSD为0.36%(n=5),日间RSD为0.95%(n=5)。结论:该方法简单、快速、准确地测定吲哚美辛的含量及有关物质,可满足吲哚美辛滴眼液的稳定性要求。     

HPLC法测定小儿氨酚匹林咖啡因片中四种成分的含量

目的:建立HPLC法同时测定小儿氨酚匹林咖啡因片中对乙酰氨基酚、咖啡因、阿司匹林及水杨酸的含量.方法:采用岛津ODS-VP色谱柱(4.6 mm×150 mm,5μm);以甲醇-0.01mol·L-1磷酸溶液(30:70)(用三乙胺调节pH值至3.1)为流动相;检测波长为220nm;流速为1.0 mL·min-1.结果:在建立的色谱条件下,对乙酰氨基酚、咖啡因、阿司匹林、水杨酸的线性范围分别为12.6～126 nag·L-1(r=0.999 9);3.0～30.0 rag·L-1(r=1.000 0);23.0～230 mg·L-1(r=0.999 8);0.115～6.9 mg·L-1(r=1.000 0).对乙酰氨基酚、咖啡因、阿司匹林的平均回收率分别为99,1%(RSD=1.32%,n=9);100.0%(RSD=0.57%,m=9);99.0%(RSD=1.09%,n=9).结论:本法简便、快捷,准确度高,专属性强,重现性好,可用于小儿氨酚匹林咖啡因片中对乙酰氨基酚、咖啡因、阿司匹林的含量测定及水杨酸的限度控制.     

口服单剂量吲哚美辛缓释胶囊的人体相对生物利用度研究

选用健康志愿者10名,随机交叉单次口服国产吲哚美辛缓释胶囊(试验品)和法国的吲哚美辛缓释胶囊(参比品),分别于服药后按规定时间取静脉血,用高效液相色谱法测定血浆中吲哚美辛浓度。结果求得参比品和试验品两种制剂的C_max)为1.46±0.26μg·ml~(-1)和1.23±0.31μg·ml~(-1);T_(max)为3.10±1.00h和3.68±1.50h;AUC为14.55±4.48μg·ml~(-1)/h和15.32±6.38μg·ml~(-1)/h;由此求得国产吲哚美辛缓释胶囊的人体相对生物利用度为102.18±15.62％,经等效性分析,两种胶囊具有生物等效性。     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol. Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects. Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing. In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.     

欧洲刺柏（Juniper）

活性成分与药理作用欧洲刺柏药用部位是其浆果，具有促水排泄、防腐、抗胃肠胀气和抗风湿作用，还可改善胃功能。用作促水排泄药可增加尿量（水丢失），但不增加钠排泄。成分萜品烯-4-醇可增加肾小球滤过率，但刺激肾。欧洲刺柏浆果对单纯疱疹病毒体外显示抗病毒活性，并具抗真菌活性。动物实验显示，欧洲刺柏浆果提取物具有堕胎、抗生育、抗炎、抗胚胎植入、降血压、升血压和降血糖作用。欧洲刺柏浆果油具有兴奋子宫的活性，以及利尿、胃肠道抗菌和刺激作用，该油对平滑肌有阻止解痉作用。     

Oral Presentations (LDD, LPES, LNM, LPAT, LNT, LPPT, LPM)

Probiotic microorganisms have been shown to provide specific health benefits when consumed as food supplements or as food components. The main problem of such products is the poor survival of the probiotic bacteria in the low pH of gastric fluid. However the use of synthetic excipients for enteric coating to prevent the exposure of microorganisms to gastric fluid is limited in food supplementary industry. Therefore the aim of this study was to develop an enteric coating formulation containing shellac as a natural polymer. Shellac possesses good resistance to gastric juice; the major disadvantage of this polymer is its low solubility in the intestinal fluid [1, 2]. Thus films containing different ratios of shellac and water-soluble polymers (sodium alginate, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidon (PVP)) or plasticizers (glycerol and glyceryl triacetate (GTA)) were prepared in order to analyse the films’ melting temperatures (T_m), the changes in enthalpy (ΔH), their capability of taking up water, and their solubility in different media. The release characteristics of the films were studied by loading pellets with Enterococcus faecium M74 and coating them with formulations containing different amounts of shellac and polymer or plasticized shellac. Using dissolution tests, performed according to USP XXXI paddle method, the resistance of the coatings to simulated gastric fluid (SGF, pH 1.2) and the release of cells in simulated intestinal fluid (SIF, pH 6.8) was investigated.The trials showed that an increasing amount of plasticizer results in a decrease of T_m and ΔH of the films whereat glycerol had a superior plasticization effect to GTA. The compatibility of films made of water-soluble polymers and shellac was also concentration dependent. HPMC and PVP showed superior compatibility with shellac compared to sodium alginate, since films containing shellac and more than 10% [w/w] sodium alginate tended to separate into two phases. In the end five formulations containing shellac and either 5% [w/w] glycerol, 10% [w/w] PVP, 20% [w/w] PVP, 10% [w/w] HPMC, or 5% [w/w] sodium alginate emerged as feasible for enteric coating purposes.