聚乙烯基吡咯烷酮翻译1

Advanced Pharmaceutical Bulletin 2013 3 1 217 225 doi http dx doi org 10 5681 apb 2013 036 http apb tbzmed ac ir Formulation CharacterizationandPhysicochemicalEvaluatin of Potassium Citrate Effervescent Tablets Abolfazl Aslani Fatemeh Fattahi Department of Pharmaceutics School of Pharmacy and Novel Drug Delivery Systems Research Center Isfahan University of Medical Sciences Isfahan Iran 配方 特性和物理化学评价柠檬酸钾泡腾片 阿布 Aslani 今天 Fattahi 制药学 制药和新型给药系统研究中心 伊斯法罕大学医学科学 伊斯法罕 伊朗 A R T I C L E I N F O A B S T R A C T Article Type Research Article Article History Received 7 November 2012 Revised 18 November 2012 Accepted 22 December 2012 ePublished 7 February 2013 Keywords Effervescent tablets Potassium citrate Direct compression method Fusion method Wet granulation method Purpose The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones Methods In this study 13 formulations were prepared from potassium citrate and effervescent base in different concentration The flowability of powders and granules was studied Then effervescent tablets were prepared by direct compression fusion and wet granulation methods The prepared tablets were evaluated for hardness friability effervescent time pH content uniformity To amend taste of formulations different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers Results Formulations obtained from direct compression and fusion methods had good flow but low hardness Wet granulation improves flowability and other physicochemical properties such as acceptable hardness effervescence time 3minutes pH 6 friability 1 water percentage 0 5 and accurate content uniformity In panel test both of combination flavors orange lemon and strawberry raspberry had good acceptability Conclusion The prepared tablets by wet granulation method using PVP solution had more tablet hardness It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates A R T I C L E I N F O 文章类型 文章历史 收到 2 012 年 11 月 7 日修改 2012 年 11 月 18 日接受 2012 年 12 月 2 2 日 ePublished 2013 年 2 月 7 日 关键词 泡腾片柠 檬酸钾直接压缩 方法融合法湿法 造粒方法 目的 本研究的目的是设计和制定柠檬酸钾的平板电脑减少草酸钙和尿酸盐肾结石患者 患有肾结石 方法 在这项研究中 13 个配方制备不同浓度的柠檬酸钾和冒泡的基地 研究了粉末和颗粒的流动性 然后泡腾片是由直接压缩 融合和湿法造粒方法 平板 电脑进行准备的硬度 易碎性 发泡时间 pH 值 含量均匀度 修改配方 使用不同 的调味剂 然后小组测试是通过使用拉丁方方法由 30 名志愿者 结果 配方获得直接压 缩和融合方法有很好的流动但硬度较低 湿法造粒改善流动性和其他物理化学属性 如可接受的硬度 泡腾时间 3 分钟 pH 6 易碎性 1 水比例 0 5 准确的含量 均匀度 在面板测试中 这两个组合口味 橙子 柠檬 和 草莓 覆盆子 有良好的可接受性 结论 通过湿法造粒方法准备的平板电脑使用 PVP 解决方案有更多的片剂硬度 它 是一种可再生的过程 适合生产的颗粒被压缩成泡腾片由于更大的团聚体 Introduction Effervescent tablets were designed to produce solutions that release carbon dioxide simultaneously Usually these tablets are prepared by compressing the active ingredients with mixture of sodium bicarbonate and organic acids such as citric and tartaric acid 1 Generally these tablets are included drugs that are solved rapidly when entered to water and they are recommended as a clear and palatable solution 2 So they can be prescribed to patients who suffered from swallow capsules or tablets 3The main advantages of effervescent tablets are quick production of solution Thus it is faster and better to absorb 4 As a source of As a source of acid citric acid is the most used acid Also other acids such as tartaric fumaric adipic malic acid and anhydrides and salts of acid can be used Potassium and sodium carbonate sodium and potassium bicarbonate arginine carbonate are used as a sources of alkali Sodium bicarbonate is one of the most used carbonate because of high solubility severe reaction and low cost 5 So excepients such as water soluble lubricants e g PEG 4000 6000 and sodium benzoate sweeteners flavorings and water soluble colors are applied 5 Polyvinylpyrolidone PVP is an effective binder of effervescent tablets It can be added as dry powder or in a wet form as an aqueous or hydroalcoholic solution Mannitol PEG 6000 and water in small amounts can be used as effective binder 5 6 泡腾片生产设计的解决方案 同时 释放出二氧化碳 通常 这些药片是由 压缩活性成分与碳酸氢钠和有机酸的 混合物 如柠檬酸和酒石酸 1 一般来 说 这些药片包含药物快速解决当进入 水和他们推荐作为一个明确的和可行 的解决方案 2 它们可以用于病人患 有吞下胶囊或药片 3 泡腾片的主要 优点是快速的生产解决方案 因此 它 是更快和更好的吸收 4 一样的酸 柠 檬酸是最常用的酸 还其他酸如酒石 的 反丁烯二酸的己二 苹果酸和酸 酐和盐的酸可以使用 和碳酸钠 钾钠 和碳酸氢钾 精氨酸碳酸盐作为碱性 碳酸氢钠的来源是一个最常用的碳酸 盐岩的溶解性高 严重的反应和低成本 5 所以 辅料如水溶性润滑剂 例如 盯住 4000 年 6000 年和苯甲酸钠 甜味剂 调味料和水溶性应用颜色 5 聚乙烯基吡咯烷酮 PVP 是一种有效的泡腾片 的粘合剂 它可以添加干粉或湿形式作为水或水 醇解决方案 甘露醇 盯住 6000 和少量的水可以 作为有效的 binder 5 6 Low relative humidity maximum of 25 or less and moderate to cool temperatures about 25 C or 77 F in the environment are essential to prevent sticking granule or tablets to tablet press machine 5 In producing direct compression method the mixtures of powder with excellent flowability and without particles segregation are needed and particle size of all raw materials should be equal It is necessary to prepare granules if particle size is small 3 7 In fusion method mostly monohydrate citric acid released its water at 54 C in order to obtain the granules by agglomeration of the particles Granulation with nonreactive solution contain of ethanol or isopropanol that the most components of tablets are insoluble in them So a very small amount of water 0 1 0 5 is active solution 5 Effervescent tablets are produced and controlled same as conventional tablets These controls are included physicochemical properties such as hardness weight variation friability solution time pH and content uniformity 5 低相对湿度 最多 25 或更少 和温和 冷却温度 约 25 C 或 77 F 在环境中 是必不可少的 以防止粘粒或平板电脑 压片机机器 5 生产直接压缩方法 与 优秀的流动性粉末的混合物 不需要隔 离粒子和粒子大小的原材料应该一律 平等 有必要准备颗粒 如果粒度很小 3 7 在融合方法中 大多是一水柠檬 酸 发布了水在 54 C 为了获得颗粒 的凝聚粒子 造粒与不反应的解决方 案包含的乙醇或异丙醇 平板电脑的大 多数组件不溶性 所以 少量的水 0 1 0 5 是积极的解决方案 5 泡腾 片生产和控制与传统的平板电脑 这 些控件包括物化性能如硬度 重量差 异 易碎性 均匀性 5 解决时间 pH 值和内容 Corresponding author Abolfazl Aslani Department of Pharmaceutics School of Pharmacy and Pharmaceutical Sciences Isfahan University of Medical Sciences Isfahan Iran Tel 98 311 7922617 Fax 98 311 6680011 Email aslani pharm mui ac ir Copyright 2013 by Tabriz University of Medical Sciences 通讯作者 阿布 Aslani 制药学 药学和制药科学学院 伊斯法罕大学医学科学 伊斯法罕 伊朗 电话 98 311 7922617 传真 98 311 6680011 电子邮件 aslani pharm mui ac ir 版权 2013 大不里士大学 的医学科学 Aslani and Fattahi Potassium citrate is very soluble in water and almost insoluble in alcohol with very salty taste Each g of potassium citrate monohydrate consists of about 9 3 mmol of potassium and 3 08 mmol of citrate 8 Potassium citrate is used to replace sodium bicarbonate in the treatment of metabolic acidosis in patients alkalizing agent of urine and symptomatic relief of mild urinary tract infections Studies were shown that it is effective in reduction of calcium oxalate and urate kidney stones formation and prevent from bone loss 9 12 So studies are shown that oral supplements of potassium prevents hyperkalaemia from it due to the high absorption from the gastrointestinal tract but slowly 12 Products of potassium citrate are available in pharmaceutical world market in the forms of tablet 5 10 and 15 mEq potassium citrate Urocit K effervescent powder 1500 mg equivalent to 13 mEq potassium citrate Effercitrate and oral solution 8 Although the mentioned dosage form are available in the pharmaceutical market none of them are held accountable for patient requirement because high doses of drug are needed for patients with calcium and urate kidney stones These patients are using the drug into two forms 1 a pharmaceutical dosage form with a low dose and high frequency consumption or 2 the bulk of the raw materials Until now in the pharmaceutical market this potassium citrate effervescent tablet with 25 meq does not exist It is a new and applications design The aim of this study is design formulation and preparation of the potassium citrate effervescent tablets containing 25 mEq monohydrate potassium citrate These tablets will help to physicians prescribing and convenience consumption for patients suffering from calcium oxalate and urate kidney stones 柠檬酸钾非常易溶于水 几乎不溶于酒精很咸的味 道 每克柠檬酸钾 一水 由 9 3 和 3 08 中毒 citrate 8 钾中毒 柠檬酸钾是用来取代碳酸氢钠治疗代谢性酸中毒 的患者 碱化尿液和症状的缓解轻微的尿路感染 研究表明 它是有效地减少草酸钙和尿酸盐肾结石 的形成和防止骨 loss 9 12 如此 研究表明 口服补 充剂可以防止高钾血症由于高钾从胃肠道吸收但 缓慢的 12 柠檬酸钾的产品可用在世界医药市场的形式 平板 电脑 5 10 和 15 毫克当量柠檬酸钾 Urocit k 发泡粉 1500 毫克相当于 13 毫克当量柠檬酸钾 埃 弗柠檬酸 和口头解决方案 8 虽然提到剂型可 在医药市场 没有一个是对病人负责的要求 因为大 剂量的药物需要钙和尿酸盐肾结石患者 这些患者使用药物分为两种形式 1 制药剂型与低 剂量 高频率消费或 2 的大部分原材料 直到现 在在医药市场 这种柠檬酸钾的平板电脑与 25 毫 克当量不存在 这是一个新的和应用程序设计 本研究的目的是设计 配方和制备柠檬酸钾的泡 腾片包含 25 毫克当量一水柠檬酸钾 这些药片将 有助于医生处方和便利消费对患有草酸钙肾结石 和尿酸盐 Materials and Methods Material Potassium citrate monohydrate sodium bicarbonate citric acid monohydrate tartaric acid PEG 6000 sodium benzoate manitol sorbitol and aspartame were procured by Merck Darmstadt Germany Povidon k 30 PVP was purchased from Rahavard Tamin Tehran Iran Orange flavoring agent was procured from Kagawa China and raspberry strawberry cherry and lemon flavoring agents were prepared by Farabi pharmaceutical Company Isfahan Iran Preformulation Firstly the formulas were made up in the different stoichiometric ratios from tartaric acid citric acid and sodium bicarbonate based on below reactions According to Table 1 materials of each formulation were weighed and then 2700 mg of monohydrate potassium citrate was added to each formulation Finally after preparation of appropriate mixture the lubricants including 30 mg of PEG 6000 and 10 mg of sodium benzoate were added the mixture and then the tablets compressed by using a single punch press machine KILIAN the amount remaining on each sieve was measured 13 The mean diameter of the powders was calculated by equation 1 预加压力测试 粒度分析 混合粉末的平均粒度是由筛分分析方法 100 克粉 混合物和颗粒倒上筛 筛系列放在艾维卡摇装置 10 分钟后这段时间 剩下的数量在每个测量 13 筛 粉末的平均直径由公式 1 计算 习 两个上部和下部的平均大小筛 di 我在有限区 域的数量的比例由两个筛子 流动性粉末流的评估 休止角 压缩指数和豪斯纳 S比率可以使用 休止角 粉末或颗粒的质量 通过漏斗 休止角是由方程 2 平均三个测量是按 照 USP NF 解释 2008 1 身高 锥形成基础的高度 直径锥形成的 压缩性指数和 Hausner s 比率 体积密度的测量 100 克的粉末和颗粒注入量筒 250 毫升 使用玻璃 漏斗和它的体积是记录 利用包含粉缸继续 直到没有进一步的体积发生变 化 利用密度是来自下面的方程 压缩性指数和 Hausner s 比值参数通过利用从 bulk 三个度量值的平均值和 tapped 根据 USP NF 2008 14 相比 Compressibility Index 压缩性指数 Hausner s Ratio Hausner s 率 Post compression Tests Measurement of Tablet Hardness Hardness of tablets was determined according to the USP for 10 tablets of each formulation by using a hardness tester Erweka 24 TB Germany Hardness of effervescent tablets is usually lower than conventional tablets and minimum of acceptable hardness of uncoated tablets is 40 N approximately 1 Measurement of Tablet Thickness The thickness of 10 tablets from each formulation was determined by using calibrated collies Average fluctuations of thickness should not exceed more than 5 of its normal limits 1 Friability 20 tablets of each formulation was taken randomly and after weighting altogether were placed in the friabilator chamber Erweka TAP Germany for 4 minutes at 25 rpm If weight loss is greater than 1 is unacceptable 1 Evaluation of Weight Variation 20 tablets of each formulation were weighed individually and the mean of weight were determined According to the USP for tablets with weight more than 324 mg among 20 tablets just two tablets can be out of the 5 of the average weight and none deviated by more than twice that percentage 14 Measurement of Effervescence Time A single tablet was placed in a beaker containing 200 ml of purified water at 20 C 1 C Whenever a clear solution without particles was obtained effervescence time has finished 15 The mean of three measurements of each formulation was reported Determination of Effervescent Solution pH pH solution was determined with one tablet in 200 ml of purified water at 20 1 C by using pH meter Metrohm 632 Switzerland immediately after completing the dissolution time 15 This experiment was repeated 3 times for each formulation 文章压缩测试 片剂硬度测量 药片的硬度决定根据每个配方的 USP 10 平板电脑 使用硬度计 Erweka 24 TB 德国 泡腾片的硬度通常是低于传统的平板电脑和未涂 布平板电脑的最低可接受的硬度是 40 N 大约 1 平板厚度的测量 10 片的厚度从每个配方决心通过使用校准柯利牧 羊犬 平均厚度波动 不应超过 5 以上的正常 limits 1 易碎性 20 每个配方的平板电脑是完全随机加权后 被安置 在脆碎度r 室艾维卡 水龙头 德国 4 分钟 25 rpm 如果减肥是不可接受 1 超过 1 评估的重量差异 20 片的每个配方分别重和平均重量测定 根据平 板电脑的 USP 体重超过 324 毫克 在 20 片 两个平 板电脑可以出 5 的平均体重 没有倾斜百分率 14 两倍以上测量时间冒泡的 一个平板电脑是放置在一个烧杯包含 200 毫升的 纯净水 20 C 1 C 每当一个明确的解决方案没有 得到粒子时间完成 15 发泡性能 平均每个配方的三个测量报告 冒泡的测定溶液的 pH 值 pH 值的解决方案是确定与一片在 200 毫升的纯净 水用酸度计 20 1 C 瑞士万通 632 年 瑞士 完成 后立即溶解时间 15 每个配方这个实验重复了 3 次 Measurement of CO2 Content One effervescent tablet solved in 100 ml of 1N sulfuric acid solution and weight changes were determined after dissolution end The obtained weight difference was shown the amount mg of CO2 per tablet The CO2 content reports are averages of 3 determinations 15 Evaluation of the Water Content 10 tablets of each formulation were dried in a desiccator containing of activated silica gel for 4 hours Water content of 0 5 or less is acceptable 15 Assay The first 3 effervescent tablets of potassium citrate was triturated and 347 mg of crushed powder Equivalent to 200 mg of anhydrous potassium citrate accurately weighed and was dissolved in 25 ml of acetic acid glacial Added 2 drops of crystal violet TS solution and titrated with 0 1N perchloric acid VS USP to a green end point The same steps was done on a blank solution prepared from effervescent tablets of potassium citrate without active ingredient and was made any necessary correction In the titration the prepared blank was consumed perchloric acid and corrected volumes were required Each ml of 0 1N perchloric acid is equivalent to 10 21 mg of anhydrous potassium citrate 14 2700 mg of hydrated potassium citrate is equivalent to 2550 194 anhydrous potassium citrate Of course in this assay other alternative methods such as atomic absorption can also be used 测量二氧化碳的含量 一冒泡的平板电脑在 100 毫升 1 n 解决硫酸溶液 和体重变化决定解散后结束 获得的重量差异显 示每个平板 mg 的二氧化碳 二氧化碳含量报告 平均 3 测定 15 评估的含水量 10 每个配方的平板电脑在一个包含活性硅胶干燥 器干燥 4 小时 接受 15 含水量的 0 5 或更少 分析 第一 3 泡腾片的柠檬酸钾齿式和 347 毫克的碎粉 相当于 200 毫克的无水柠檬酸钾 准确称重 并溶 解在 25 毫升的冰醋酸 添加 2 滴结晶紫 TS 解决 方案和 0 1 n 高氯酸滴定 VS USP 绿色终点 同样 的步骤做了一个空白的解决方案准备泡腾片的柠 檬酸钾没有活性成分和任何必要的调整 滴定 准 备空白需要消耗高氯酸和纠正卷 每毫升 0 1 n 高 氯酸相当于 10 21 毫克的无水柠檬酸钾 14 2700 毫克的水合柠檬酸钾相当于 2550 194 无水柠檬酸 钾 当然 在这个分析原子吸收等其他替代方法也 可以使用 N V 纠正了空白 护士 正常的标准化酸钾苯二甲酸氢盐根据 USP mg 毫克的水合柠檬酸钾 108 14 水合柠檬酸钾的 情商 Evaluation of Content Uniformity 10 tablets of each formulation were selected at random to measurement of the active ingredient amount None of the tablets should not be out of range 90 110 of mention amounts in formula and coefficient of variation CV should not be more than 6 If only one tablet was out of previous range and range of 80 120 20 tablets must be tested Among these 20 tablets anything of them should not be out of range 90 110 percent 14 Determination of the Equilibrium Moisture Content Three desiccators were prepared containing saturated salt solutions of potassium nitrate for creation 90 RH at 18 C sodium chloride for creation 71 RH at 18 C and sodium nitrite for creation 60 RH at 18 C Three tablets of each formulation were placed in desiccators Then the equilibrium moisture content was determined by Karl Fischer method and the autotitrator device Mettler TOLEDO DL53 Switzerland in the first day and after 7 day 14 Evaluation of Prepared Tablets Taste Before beginning the evaluation the taste ability of volunteers was measured by four base tastes salt sweet sour bitter by 20 ml of 0 2 sodium chloride 2 sucrose 0 07 citric acid and 0 07 caffeine in water respectively 16 To evaluate the taste panel tests were performed by Latin Square method The first with the help of 5 volunteers 7 flavors which were added to F6 formulation optimum formulation were examined Table 3 Thus the volunteers were asked to score each of the formulation from 1 very bad 2 bad 3 no taste 4 good and 5 excellent taste based on Likert Scale At next stage another 30 volunteers were asked to give points to the 2 selected flavors of early stages from 1 very bad 2 bad 3 no taste 4 good and 5 excellent taste based on Likert Scale 评价内容的一致性 10 每个配方的平板电脑随机选择活性成分的测量 所有的平板电脑不应该的范围 90 110 年 提到 大量的公式 和变异系数 CV 不应超过 6 如果只 有一个平板电脑之前的范围和范围的 80 120 20 平板电脑必须测试 其中 20 平板电脑 什么都不应该出 90 110 百分率 14 范围 平衡含水率的测定 三个干燥器制备含有饱和盐解决方案的硝酸钾 创 造 90 RH 18 C 氯化钠 创造 71 RH 18 C 亚硝酸钠 创造 60 RH 18 C 三个每个配方被 放置在干燥器的平板电脑 然后 平衡含水率是由 费歇尔法和汽车的硝酸盐r 设备 瑞士梅特勒 TOLEDO DL53 和 7 day 14 后的第一天 评估准备药片的味道 在开始评估之前 志愿者的味觉能力是衡量四个基 本口味 盐 甜 酸 苦 20 毫升的 0 2 氯化钠 蔗糖 2 柠檬酸 0 07 水分别的 16 0 07 的咖 啡因 评估的味道 面板测试是由拉丁方的方法 第一 5 名志愿者的帮助下 7 口味被加入 F6 配方 最佳配 方 检查 表 3 因此 志愿者们被要求分数每个配 方从 1 非常糟糕 2 坏 3 没有味道 4 好 5 优秀的基于李克特量表的味道 在下个阶段 另一个 30 名志愿者被要求给点 2 选 择口味的早期阶段从 1 非常糟糕 2 坏 3 没有 味道 4 好 5 优秀的基于李克特量表的味道 In all time of experiments the standard conditions of panel test were considered such as temperature equal to 21 C 20 minutes distance from the previous samples samples with similar concentrations of drugs and have been done without exchanging the volunteers idea 16 Results Results of preformulation study is shown that formulations with stoichiometric ratios 1 1 and 1 5 1 5 S5 S11 were selected as the appropriate base formulations in tableting process and with better physicochemical characteristics Results from characterization of the powder formulations containing of the particle size distribution angle of repose compressibility index and Hausner s ratio are given in the Tables 4 5 and Figure 1 The results of obtained from tablets evaluation are presented for hardness friability tablet thickness effervescence time pH weight variation water and CO2 content content uniformity and equilibrium moisture content properties are given in the Tables 5 6 8 too The particle size distribution of three manufacturing methods is listed in Tables 4 and 5 The mean diameters of granules were greater than the powders Figure 1 shows the particle size distribution diagram of F5 formulation which has normal distribution 表 3 不同的口味被用于板试验的柠檬酸钾泡腾片 Raspberry Strawberry Cherry Orange Lemon F Orange much ability will have to absorb moisture Consequently possibility of effervescent reaction beginning and instability is high in these tablets So it is necessary to determined that the provided tablets are stable up to pH 值小于 6 是必要泡腾