溶出度检查法美国药典USP711.docx

1、溶出度检查法美国药典USP711 DISSOLUTION溶出度(USP39-NF34 Page 540)General chapterDissolutionis being harmonized with the corresponding texts of theEuropean Pharmacopoeiaand/or theJapanese Pharmacopoeia. These pharmacopeias have undertaken to not make any unilateral change to this harmonized chapter.通则溶出度与欧盟药典和日本药

2、典中的相应部分相统一。这三部药典承诺不做单方面的修改。Portions of the present general chapter text that are nationalUSPtext, and therefore not part of the harmonized text, are marked with symbols to specify this fact.本章中的部分文字为本国USP容，并没有与其他药典统一。此部分以（）标注。This test is provided to determine compliance with the dissolution require

3、mentswhere stated in the individual monographfor dosage forms administered orally. In this general chapter, a dosage unit is defined as 1 tablet or 1 capsule or the amount specified.Of the types of apparatus designs described herein, use the one specified in the individual monograph. Where the label

4、 states that an article is enteric coated and a dissolution or disintegration test does not specifically state that it is to be applied todelayed-releasearticles and is included in the individual monograph, the procedure and interpretation given forDelayed-Release Dosage Formsare applied, unless oth

5、erwise specified in the individual monograph.本测试用于检测药品口服制剂的溶出度是否符合各论中的规定。本章中，除另有规定外，单位制剂定义为1片或1粒胶囊。对于本章中所述多种仪器，使用各论中规定的种类。除各论中另有规定外，如果检品是肠溶衣片且各论中的溶出度或崩解时限检查项下没有特别指出适用迟释剂的，使用本章中适用于迟释剂的流程和解释。FOR DOSAGE FORMS CONTAINING OR COATED WITH GELATIN涂有或包含明胶的剂型If the dosage form containing gelatin does not meet

6、 the criteria in the appropriateAcceptance Table(seeInterpretation,Immediate-Release Dosage Forms,Extended-Release Dosage Forms, orDelayed-Release Dosage Forms) because of evidence of the presence of cross-linking, the dissolution procedure should be repeated with the addition of enzymes to the medi

7、um, as described below, and the dissolution results should be evaluated starting at the first stage of the appropriateAcceptance Table. It is not necessary to continue testing through the last stage (up to 24 units) when criteria are not met during the first stage testing, and evidence of cross-link

8、ing is observed.如果剂型中含有明胶，其不符合验收表中的标准（见判断，速释制剂，延释制剂，缓释制剂），因为存在明胶交联结合作用，它的溶解过程与外加的媒介酶是重复的，见下面的描述，并且溶解结果可以通过适当的验收表的开始的第一阶段标准进行评估。如果溶出结果不满足第一阶段的测试标准，那么就没有必要继续测试到最后阶段，并且也证明了明胶交联结合作用的存在。Gelatin, in the presence of certain compounds and/or in certain storage conditions, including but not restricted to hig

9、h humidity and temperature, may present cross-linking. A pellicle may form on the external and/or internal surface of the gelatin capsule shell or on the dosage form that prevents the drug from being released during dissolution testing (see more information inCapsulesDissolution Testing and Related

10、Quality Attributes).明胶，存在于某一处方和/或某一储存条件下，如：高温高湿，可能存在明胶交联结合作用。在胶囊壳或其他剂型的外表面和/或表面形成一层膜阻止溶出试验过程中药物的释放（见胶囊-溶出度检测和相关质量属性）。NoteAll references to a chapter aboveare for information purposes only, for use as a helpful resource. These chapters are not mandatory unless explicitly called out for this applicati

11、on.注-超过章节的所有引用应用的目的仅为提供参考信息。这些章节是非强制的，除非另有规定。Dissolution Medium with pH4.0 pH4.0的溶出介质Enzyme:Pepsin, activity determined by the procedure inpurified pepsin, in theReagent Specificationssection酶：胃蛋白酶，活性视试剂规格部分中的胃蛋白酶提纯过程而定。Amount:A quantity of pepsin that results in an activity of NMT 750,000 Units/L o

12、f dissolution medium数量：一些胃蛋白酶对溶出介质提供NMT 750,000 单位/L的生物活性。Dissolution Medium with pH 4.0 and 4.0 和 6.8的溶出介质Enzyme:Papain, activity determined by theAssaytest in the monograph forPapain; or bromelain, activity determined by the procedure inbromelain, in theReagent Specificationssection酶：木瓜蛋白酶，活性视木瓜蛋白

13、酶专论中的分析测试而定；或菠萝蛋白酶，活性视试剂规格部分中的菠萝蛋白酶生产过程而定。Amount:A quantity of papain that results in an activity of NMT 550,000 Units/L of dissolution medium, or a quantity of bromelain that results in an activity of NMT 30 gelatin-digesting units (GDU)/L of dissolution medium数量：一些木瓜蛋白酶对溶出介质提供NMT 550,000 单位/L的生物活性

14、；一些菠萝蛋白酶对溶出介质提供NMT 30明胶消化单位/L的生物活性。Dissolution Medium with pH6.8 pH6.8的溶出介质Enzyme:Pancreatin, protease activity determined by the procedure inAssay for protease activity(Casein digestive power) in the monograph forPancreatin酶：胰液素，蛋白酶活性视胰液素专论中的蛋白酶活性（酪蛋白消化能力）分析中的生产过程而定。Amount:A quantity of pancreatin

15、that results in a protease activity of NMT 2000 Units/L of dissolution medium数量：一些胰液素对溶出介质提供NMT 550,000 单位/L的蛋白酶活性。Dissolution Medium Containing Surfactant or Other Ingredients Known to Denature the Enzyme含有表面活性剂或其他已知成分变性酶的溶出介质If the dissolution medium contains surfactant or other ingredients that a

16、re known to denature the enzyme used, a pretreatment step in the dissolution testing of the dosage form may be applied. This pretreatment step is done using the specified dissolution medium without the surfactant or the ingredient and with the addition of the appropriate amount of enzyme according t

17、o the medium pH. The amount of enzyme added is appropriate to the volume of dissolution medium used in the pretreatment. To achieve the specified medium volume for the final dissolution testing, the pretreatment step may be conducted with a smaller volume of medium without the ingredient such that t

18、he final volume is obtained when the ingredient is added at the end of the pretreatment step. All of the other conditions of the test (apparatus, rotation, or flow rate) should remain as described in the method or monograph. Typically, the duration of the pretreatment step is NMT 15 min. The require

19、d pretreatment time should be evaluated on a case-by-case basis and should be scientifically justified. This time should be included in the total time of the test. As an example, if the total time of the test is 45 min and 15 min are used in the pretreatment step, the test will continue for 30 min a

20、fter the addition of the ingredient.如果溶出介质中添加了表面活性剂或其他已知成分的变性酶，那么此溶出实验就要把预处理步骤考虑进去。预处理过程就是是根据溶出介质的pH来确定加入酶的量，此处的溶出介质不含有表面活性剂和原料。酶加入的量要适合预处理所用的溶出介质的体积。为了达到最终溶出试验所需要的特定的溶出介质的体积，预处理阶段所用的溶出介质（不含原料）的体积要稍微小点，如此在预处理最后阶段加入原料的时候方可获得最终的溶出介质体积。其他所有的测试条件（如：设备、转速、流速）应该与方法或专论中描述的一致。通常预处理阶段的持续时间为NMT 15 min。所需的预处理时

21、间应该根据具体案例具体分析，且应该科学、合理。预处理时间应该包含在实验的总时间里。例如，如果实验的总时间为45min，预处理时间为15min，那么加入原料后实验还要继续进行30min。USP Reference Standards11USP Prednisone Tablets RS.USP参考标准-USP强的松片 RS。APPARATUS仪器Apparatus 1 (Basket Apparatus) 第1法（篮法）The assembly consists of the following: a vessel, which may be covered, and made of glass

22、 or other inert, transparent material;1a motor; a metallic drive shaft; and a cylindrical basket. The vessel is partially immersed in a suitable water bath of any convenient size or heated by a suitable device, such as a heating jacket. The water bath or heating device permits holding the temperatur

23、e inside the vessel at 37 0.5 during the test and keeps the bath fluid in constant, smooth motion. No part of the assembly, including the environment in which the assembly is placed, contributes significant motion, agitation, or vibration beyond that due to the smoothly rotating, stirring element. A

24、n apparatus that permits observation of the specimen and of the stirring element during the test is preferable. The vessel is cylindrical, with a hemispherical bottom andwith one of the following dimensions and capacities: for a nominalcapacity of 1 L, the height is 160210 mm, and its inside diamete

25、r is 98106 mm;for a nominal capacity of 2 L, the height is 280300 mm, and its inside diameter is 98106 mm; and for a nominal capacity of 4 L, the height is 280300 mm, and its inside diameter is 145155 mm. Its sides are flanged at the top. A fitted cover may be used to retard evaporation.2The shaft i

26、s positioned so that its axis is NMT 2 mm at any point from the vertical axis of the vessel and rotates smoothly and without significant wobble that could affect the results. A speed-regulating device is used that allows the shaft rotation speed to be selected and maintained at the specified rategiv

27、en in the individual monographwithin 4%.设备由下列部分组成：有盖或无盖的溶出杯，由玻璃或其他惰性的透明材料1制成；马达；转轴；转篮。溶出杯部分浸没在合适大小的水浴中，或者由合适的装置加热，例如电热套。水浴或加热装置需能在测试过程中将杯温度保持在370.5，并且容许杯液体持续、平缓的流动。整个仪器包括周围的环境，除了平稳转动的搅拌部件，不得有明显的运动，搅动或振动。仪器最好能允许在检测过程中能够观察到检品和搅拌部件。溶出杯为圆柱形，底部为半球形，尺寸和容积如下：名义容积1L的，高160-210mm，径98-106mm；名义容积2L的，高280-300mm，

28、径98-106mm；名义容积4L的，高280-300mm，径145-155mm。壁顶部有缘。可以使用合适的盖子减缓溶剂蒸发2。转轴与溶出杯的纵轴在任意部位不得相差差过2mm，转动平滑，无明显摇晃以至于影响检测结果。速度调节装置控制转轴的转速，并可维持在各论中规定值的4%围。Shaft and basket components of the stirring element are fabricated of stainless steel, type 316, or other inert material, to the specifications shown inFigure 1. A

29、 basket having a gold coating of about 0.0001 inch (2.5 m) thick may be used. A dosage unit is placed in a dry basket at the beginning of each test. The distance between the inside bottom of the vessel and the bottom of the basket is maintained at 25 2 mm during the test.转轴和篮筐组件由316号不锈钢或者其他惰性材料制成，尺寸

30、如图1所示。可使用镀金厚度0.0001英寸（2.5m）的篮筐。开始检测时，将一剂药品至于干燥的篮筐中。在测试过程中，溶出杯底部到篮筐底部的距离应保持在252mm。Figure 1. Basket stirring element.图1. 转篮组成Apparatus 2 (Paddle Apparatus) 第2法（桨法）Use the assembly fromApparatus 1, except that a paddle formed from a blade and a shaft is used as the stirring element. The shaft is positi

31、oned so that its axis is NMT 2 mm from the vertical axis of the vessel at any point and rotates smoothly without significant wobble that could affect the results. The vertical center line of the blade passes through the axis of the shaft so that the bottom of the blade is flush with the bottom of th

32、e shaft. The paddle conforms to the specifications shown inFigure 2. The distance of 25 2 mm between the bottom of the blade and the inside bottom of the vessel is maintained during the test. The metallic or suitably inert, rigid blade and shaft compose a single entity. A suitable two-part, detachable design may be used, provided that the assembly remains firmly engaged during the test. The pad