洛伐他汀片溶出度测定的研究

目的：建立洛伐他汀片溶出度检测的新方法,方法：桨法,以０．５％十二烷基硫酸的磷酸二氢钠溶液为溶剂,采用紫外分光光度法测定,检测波长２３８ｎｍ。结果：线性范围２～１４ｕｇ．ｍｌ＾－１,ｒ＝１．００００,回收率９９．８％,ＲＳＤ＝０．２％。结论：方法简便,结果准确,可作为该品种溶出度测定的检测方法。     

对照品法与自身对照法差异性研究——格列喹酮片药物溶出度方法学探讨

目的：考察引起溶出度结果差异的原因，进一步探讨合理的分析方法。方法：用格列喹酮对照品和药片粉分别配置系列溶液，于同一坐标系内建立标准曲线并进行比较。使用光纤药物溶出仪应用两种标准曲线方程时，比较格列喹酮片的溶出度差异。结果：格列喹酮片粉溶液中加入二甲基甲酰胺（DMF）助溶，不同温度下过滤时格列喹酮均不损失。采用光纤药物溶出仪检测格列喹酮片溶出度，可避免由于过滤操作引起的误差。结论：制备自身对照溶液应根据具体情况适量加入助溶剂，此外，取样分析应及时过滤，检测。光纤药物溶出仪实时、在线、过程检测药物溶出度，检测结果直观、真实、准确、快捷。     

药物溶出度测定仪的研究进展

药物溶出度试验是评价制剂品质和工艺水平的有效手段,也是检测固体制剂活性成分生物利用度和均匀度的一种有效方法．而所用的药物溶出度测定仪则是药典规定的检测固体药物制剂在规定的溶剂中溶出的速度和程度的专用仪器,因此,药物溶出度测定仪在评价药物溶出度时起着重要作用。本文就目前溶出度测定仪的优缺点进行总结,并对未来智能化药物溶出度测定仪的研制提出了新思路。     

光纤药物在位溶出度／释放度监测仪实时监测复方卡托普利片体外溶出度

目的：采用光纤化学传感技术实时、在位监测固体制剂体外溶出度的测定并与中国药典2000年版方法比较。方法：分支光纤一端连接光源，公共端部探头浸入溶出液，另一端连接检测器，计算机记录并处理数据。结果：本法监测药物溶出的全过程，显示药物实时溶出曲线图，直接提取相关参数，与药典方法比较，无统计学差异（p〉0．05）。结论：光纤化学溶出度过程监测法能够有效的测定固体药物的体外溶出度，并能真实地反映药物溶出的全过程。     

过程分析考察不同厂家盐酸维拉帕米片的溶出度

目的：利用光纤溶出度过程分析方法,监测盐酸维拉帕米片的溶出度,反映不同厂家及同一厂家不同批号盐酸维拉帕米片间的质量差异.方法：采用《中国药典》盐酸维拉帕米片溶出度检测方法中的条件,利用光纤传感溶出度实时过程分析方法考察4个不同厂家及同一厂家5个不同批号盐酸维拉帕米片的溶出度.结果：过程溶出曲线反映每一药片溶出过程全部信息.4个不同厂家盐酸维拉帕米片的溶出度均符合《中国药典》2010年版规定,但溶出速度和曲线存在差异.结论：光纤溶出度过程分析原位实时反映了药物体外溶出特性,并真实地反映了同一药物的药片存在明显的差异.对考察体内外相关性、评价药品品质和评价生物等效性提供了有效途径.     

微粉化原料药的比卡鲁胺片的溶出度研究

目的：建立比卡鲁胺片溶出度试验的方法，并考察微粉化比卡鲁胺片溶出度的改善情况。方法：使用溶出度试验法Ⅱ法，采用紫外分光光度法测定溶出度。分别以pH6．8磷酸盐缓冲溶液和不同浓度的十二烷基硫酸钠溶液（0．1％，0．25％，0．5％，1％）为溶出介质，体积为1000mL，桨法，转速50r·min^-1，比较比卡鲁胺片的溶出行为。结果：经过气流微粉化加工成平均粒径为3．6μm的比卡鲁胺原料药压制成薄膜衣片自制片和进口片在上述溶剂中的溶出行为相似，而未经微粉化的自制片的溶出极差。结论：通过微粉化技术能够提高难溶性药物的溶出度，达到进口产品一样的效果。     

不同厂家辛伐他汀口服制剂溶出度比较

目的 考察国内不同厂家辛伐他汀口服制剂的体外溶出度情况，并同默沙东公司产品进行比较。方法 色谱柱为Waters symmetry C18柱，流动相为乙腈-pH值为4．5的0．025mol／1。磷酸二氢钠（65：35），流速为1．6mL／min，检测波长为238min，测定不同厂家的9个品种的体外溶出度，采用SPSS对各组之间溶出度值的方差齐性进行检查，结果 辛伐他汀浓度线性范围是1．592—25．47μg／ml。（r=0．9999），平均加样回收率为99．8％（RSD=0．68％），各个品种的溶出度都大于80％，但各组溶出度方差差异较大，结论 不同厂家辛伐他汀口服制溶出度都符合要求，但溶出度均一性差异较大，舒降之各样品之间的体外溶出度差异最小。     

药物溶出度试验的应用和进展

目的：阐述溶出度试验在药物中的应用和进展。方法：查阅资料，选取有代表性的文献进行综述。结果：叙述了溶出度试验使用的仪器、溶出试验的方法、溶出介质的选择和溶出量测定的方法。论述了溶出度试验在片剂、胶囊剂、栓剂、微丸、固体分散体、丸剂、滴丸、微球、泡腾颗粒剂、凝胶剂、烧伤膜和眼用药膜等制剂中的应用和进展。结论：说明了溶出度试验在药物固体制剂中的应用具有重要的意义。     

尼美舒利干混悬剂溶出度检查方法研究

目的：建立尼美舒利干混悬剂溶出度检查方法。方法：参照中国药典2005年版二部溶出度测定法第二法，以磷酸盐缓冲液（pH8．8）为溶出介质，40min时取样，用紫外-可见分光光度法检测溶出量，检测波长为393nm。结果：尼美舒利在2-20mg·L^-1范围内溶液浓度与吸收值呈良好线性关系（r=0．9999）；平均回收率为99．6％（n=9，RSD为0．51％）；测定溶液在8h内稳定；样品的溶出均一性良好，RSD为3．86％，40min时平均溶出率为88．2％。结论：该方法简便易行、准确可靠，可用于尼美舒利干混悬剂溶出度检查.     

多通道光纤化学传感器连续在位检测氧氟沙星片的溶出度

目的：采用基于荧光多猝灭原理的多通道光纤化学传感器连续在位检测氧氟沙星片的溶出度。方法：用自制光纤荧光溶出度监测仪与ZRS－4型智能溶出仪联用，连续在位检测氧氟沙星片的溶出度，溶出曲线经微机从5种常用数学模型中根据相关系数，优选最佳模型进行拟合。结果：方法的回收率为97．4％－104．4％，日内、日间的RSD均小于5％。经与中国药典2000年版方法对照，各时间氧氟沙星积溶出量和拟合后提取的参数均无显著性差异（P＞0．05）。结论：本法简便、快速，结果准确、可靠，重现性好。     

A biorelevant dissolution stress test device – background and experiences

Importance of the field: The prediction of the in vivo drug release characteristics of modified release (MR) oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development.

Areas covered in this review: To improve the predictive power of dissolution testing, the authors recently developed a new dissolution test apparatus that simulates physical conditions of the gastrointestinal (GI) passage of MR dosage forms. The simulation includes pressure force exerted by GI motility, shear stress force generated during phases of GI transport and intermittent contact with intestinal fluids while the dosage form is located in an intestinal air pocket.

What the reader will gain: The article briefly describes selected aspects of GI tract physiology, evolution and goals of dissolution testing as well as the development and use of test devices that are intended to simulate GI tract conditions. The data are discussed in the light of the test results obtained with the new dissolution stress test device developed by the authors' group. Achievements reported from 1986 to 2010 are referred to.

Take home message: The new apparatus was evaluated using extended release (ER) tablets of nifedipine and diclofenac. The dissolution characteristics of some of the tested products were strongly dependent on the test conditions and could be distinctly influenced by the mechanical stress events of biorelevant intensity. Results of these experiments thus indicated that a high sensitivity of dosage forms to GI-specific physical conditions has to be regarded as a major cause of irregularities in the drug release profiles, which may result in fluctuations of the individual drug plasma concentration profiles, as, for example, caused by dose dumping.     

药物固体制剂的溶出度测定研讨会随笔

中国药学会《药物分析杂志》和德国法兰克福大学制药技术学院于2007年9月分别在北京和上海联合主办了药物固体制剂的溶出度测定研讨会。本文总结了研讨会有关专家对溶出度技术的研究、应用和发展演讲的内容。     

光纤药物溶出度法测定盐酸环丙沙星片及胶囊的溶出度

目的用光纤溶出度法测定和分析不同生产厂家和批号的盐酸环丙沙星片及胶囊溶出度,以此为例,探索固体制剂药物溶出过程的评价方法。方法采用光纤溶出度实时测定和《中国药典》规定的药物溶出度测定方法,比较2种方法测得的溶出百分率与药物相对标示量的百分含量之间的差异;提取FODT测定该制剂的溶出曲线,以及开始、中间及终末溶出3个阶段4项参数,并比较这些曲线和参数;考察相似因子（f2因子）及A值评价药物溶出过程的方法;同时观察该制剂在不同溶出介质中的溶出行为。结果 FODT 30min溶出百分率高出《中国药典》约4%,更接近药物相对百分含量;该制剂溶出曲线总体分为＂厂＂型和＂S＂型,2种溶出曲线类型的4项溶出参数有所不同;相对试验结果：f2与A值评定结果不一;盐酸环丙沙星片在磷酸盐缓冲液中几乎没有溶出。结论本试验结果表明：不同生产厂家批号的盐酸环丙沙星片及胶囊的药物溶出过程差异较大,应当建立简单实用的固体制剂溶出度的评价方法。     

应用光纤药物溶出仪对硝苯地平缓释片释放度的考察

目的:对硝苯地平缓释片进行全程的实时、原位在线释放度测定,并与该品种已有国标[1]释放度测定结果进行比较.方法:运用FODT-601光纤药物溶出仪,选择237/550 nm双波长法,消除赋形剂干扰,按该品种已有国标释放度检查项溶出条件,测试该药物溶出曲线,并与按国标方法测得的溶出曲线进行比较.结果:在3.37μg·mL-1～17.83μg·mL-1范围内,浓度(C)与吸光度(A)呈良好的线性关系,浓度对应的溶出量(Q)% 与吸光度(A)也呈良好的线性关系,相关系数均在0.9990以上;3个浓度各3份样在6个通道的平均回收率分别为98.52%、99.22%、98.78%;对应的RSD(n=18)分别为1.1%、0.7%、0.7%,溶出曲线与国标方法测定的溶出曲线无显著性差异(P>0.05).结论:硝苯地平缓释片光纤药物溶出仪测定结果与按常规国标方法测定结果基本一致,而且该法具有操作简便,测定快速,获取信息量更大的优点.     

In vitro dissolution medium with supramicellar surfactant concentration and its relevance for in vivo absorption

Use of a dissolution medium with supramicellar surfactant concentration is proposed for the in vitro testing of practically insoluble drugs (less than 0.01%). Based on the fact that the model drug tested—palmitoylcatechin—is absorbed in the intestine, a pH 6.8 phosphate buffer (Pharm. Eur.) with the addition of 50 mmol/1 sodium laurylsulfate was used in our work. At that concentration, this surfactive agent had similar solubilizing properties toward the drug as the natural bile salts sodium cholate and sodium taurocholate. Five experimental and commercial palmitoylcatechin preparations, namely four tablet and one capsule formulations, were tested. A preliminary disintegration stage in simulated gastric fluid (a 30-min period was adopted here) was sometimes necessary in order to better correlate dissolution and in vivo absorption data.     

Increased Dissolution Rate and Bioavailability Through Comicronization with Microcrystalline Cellulose

Micronization is a commonly used enabling technology to improve the bioavailability of compounds where absorption is dissolution rate limited. However, decreasing particle size often results in increased Van der Waals' interactions and electrostatic attraction between particles. This causes agglomeration of particles, thereby compromising the increase in surface area gained by micronization. Comicronization with excipients has been reported to offer significant advantages over neat micronization. The present work describes the comicronization of a model compound CI-1040 at a high drug load that shows an increase in the dissolution rate and bioavailability in male Wistar rats. Physicochemical characterization of the comicronized and neat micronized material is presented to help explain the in-vitro and in-vivo data.     

Oral Dosage Form Performance Tests: New Dissolution Approaches

No Heading The performance test is one of a series of tests that compose the specification in a United States Pharmacopeia (USP) dosage form monograph. For an orally administered, nonsolution dosage form, it is usually satisfied by either a dissolution or disintegration procedure. Dissolution acceptance criteria are usually set in private negotiations between an applicant and a regulatory agency. With information about this private agreement and other information provided in a sponsors Request for Revision to USP, the USPs Council of Experts elaborates a public dosage form monograph. Based on the relationship between the regulatory decisions and the Request for Revision, the USP dissolution procedure links to a regulatory judgment about bioavailability and bioequivalence and, ultimately, to a judgment about safety and efficacy. The current dissolution procedure and acceptance criteria are perceived as having worked well over the years and are generally accepted. This article discusses new approaches that merit consideration. These approaches focus on a) explicit use of hypothesis testing, b) use of parametric tolerance intervals, c) improved ways to set dissolution acceptance criteria, and d) a more flexible protocol to assess conformity. Application of the proposed approaches may better assess, manage, and communicate both manufacturer and consumer risk for dissolution testing.     

肝内局部用FMC Seakem HGT Agarose-卡铂合剂的体外释放试验

OBJECTIVETo investigate sustained release tested in vitro FMC SeaKem HGT Agarose-carbplatin mixture for the local intra-live. METHODTo establish the mode of the dissolution rate testing for the drug implanting in the local intra-liver. Improved the Flo     

不同厂家苯磺酸左旋氨氯地平片的含量、有关物质及溶出度评价

目的 对5种市售苯磺酸左旋氨氯地平片进行质量评价,为临床用药提供参考。方法 测定了5个厂家各1批次的苯磺酸左旋氨氯地平片的含量、有关物质及溶出度,并与络活喜进行比较。结果 5种市售苯磺酸左旋氨氯地平片1种杂质超标,3种与络活喜生物不等效可能性较大,1种在含量、有关物质及溶出度方面最接近络活喜。结论 市售不同厂家的国产苯磺酸左旋氨氯地平片质量存在显著差异。