（1092）溶出度试验的开发和验证【中英文对照版】
INTRODUCTION
前言
Purpose 目的
The Dissolution Procedure: Developmentand Validation <1092> provides a comprehensive approach covering items to considerfor developing and validating dissolution procedures and the accompanyinganalytical procedures. It addresses the use of automation throughout the testand provides guidance and criteria for validation. It also addresses thetreatment of the data generated and the interpretation of acceptance criteriafor immediate- and modified-release solid oral dosage forms.
溶出实验:开发和验证（1092）指导原则提供了在溶出度方法开发和验证过程中以及采用相应分析方法时需要考虑的因素。本指导原则贯穿溶出度实验的全部过程，并对方法提供了指导和验证标准。同时它还涉及对普通制剂和缓释制剂所生成的数据和接受标准进行说明。
Scope 范围
Chapter <1092> addresses the development andvalidation of dissolution procedures, with a focus on solid oral dosage forms.Many of the concepts presented, however, may be applicable to other dosageforms and routes of administration. General recommendations are given with theunderstanding that modifications of the apparatus and procedures as given in USPgeneral chapters need to be justified.
<1092>章节讨论了溶出度实验的开发和验证，重点是口服固体制剂。所提出的许多概念也可能适用于其他剂型和给药途径。关于设备和方法的修改部分在USP通则中给出了合理的说明。
The organization of <1092> follows the sequence of actions often performed inthe development and validation of a dissolution test. The sections appear inthe following sequence.
在进行溶解度实验的开发和验证时，常遵循指导原则<1092>，具体内容如下： 1. PRELIMINARY ASSESSMENT (FOR EARLY STAGES OF
PRODUCTDEVELOPMENT/DISSOLUTION METHOD DEVELOPMENT) 1.前期评估（对产品开发以及溶出度方法开发的前期研究评估） 1.1 Performing Filter Compatibility 1.1滤膜相容性研究
1.2 Determining Solubility and Stability of DrugSubstance in Various Media 1.2原料药在不同溶出介质中溶解度测定和稳定性研究
1.3 Choosing a Medium and Volume 1.3溶出介质和体积选择 1.4 Choosing an Apparatus
1.4溶出设备选择（桨法和篮法以及其他方法） 2. METHOD DEVELOPMENT 2.方法开发 2.1 Deaeration 2.1脱气 2.2 Sinkers 2.2沉降篮 2.3 Agitation 2.3转速 2.4 Study Design 2.4研究设计 2.4.1 TimePoints 2.4.1取样时间点 2.4.2 Observations 2.4.2观察 2.4.3 Sampling 2.4.3取样 2.4.4 Cleaning 2.4.4清洗 2.5 Data Handling 2.5数据处理
2.6 Dissolution Procedure Assessment 2.6溶出方法评估 3. ANALYTICAL FINISH 3.完成分析
3.1 Sample Processing 3.1 样品处理 3.2 Filters 3.2 过滤 3.3 Centrifugation 3.3 离心
3.4 Analytical Procedure 3.4 分析方法
3.5 Spectrophotometric Analysis
3.5 光谱分析 3.6 HPLC 3.6HPLC法 4. AUTOMATION 4.自动化
4.1 Medium Preparation 4.1介质的配制
4.2 Sample Introduction and Timing 4.2定时进样
4.3 Sampling and Filtration 4.3取样和过滤 4.4 Cleaning 4.4 清洗
4.5 Operating Software and Computation of Results 4.5操作软件和计算的结果 5. VALIDATION 5.验证
5.1 Specificity/Placebo Interference 5.1专属性/安慰剂（辅料）干扰 5.2 Linearity and Range 5.2线性和范围 5.3 Accuracy/Recovery 5.3准确度/回收率 5.4 Precision 5.4精密度
5.4.1 REPEATABILITY OF ANALYSIS 5.4.1重复性
5.4.2 INTERMEDIATE PRECISION/RUGGEDNESS 5.4.2中间精密度/耐用性 5.4.3 REPRODUCIBILITY 5.4.3重现性 5.5 Robustness 5.5耐用性
5.6 Stability of Standard and Sample Solutions 5.6样品溶液和标准溶液的稳定性 5.7 Considerations for Automation 5.7自动操作注意事项
6. ACCEPTANCE CRITERIA 6.可接受标准
6.1 Immediate-Release Dosage Forms 6.1速释剂型
6.2 Delayed-Release Dosage Forms 6.2延迟释放剂型
6.3 Extended-Release Dosage Forms 6.3延长释放剂型
6.4 Multiple Dissolution Tests 6.4多个溶解度试验
6.5 Interpretation of Dissolution Results 6.5溶出结果说明
6.5.1 IMMEDIATE-RELEASE DOSAGE FORMS 6.5.1即时释放剂型
6.5.2 DELAYED-RELEASE DOSAGE FORMS 6.5.2延迟释放剂型
6.5.3 EXTENDED-RELEASE DOSAGE FORMS 6.5.3延长释放剂型
1. PRELIMINARYASSESSMENT (FOR EARLY STAGES OF PRODUCT DEVELOPMENT/DISSOLUTION METHODDEVELOPMENT) 1. 前期评估（产品开发/溶出度方法开发的初期阶段）
Beforemethod development can begin, it is important to characterize the molecule sothat the filter, medium, volume of medium, and apparatus can be chosen properlyin order to evaluate the performance of the dosage form.
在开始溶出方法开发之前，我们对用以评价制剂溶出行为的滤膜、溶出介质、溶出介质体积和溶出设备进行适当的筛选是非常重要的。 1.1 Performing Filter Compatibility 1.1滤膜相容性研究
Filtrationis a key sample-preparation step in achieving accurate test results. Thepurpose of filtration is to remove undissolved drug and excipients from thewithdrawn solution. If not removed from the sample solution, particles of thedrug will continue to dissolve and can bias the results. Therefore, filteringthe dissolution samples is usually necessary and should be done immediately ifthe filter is not positioned on the cannula.
为获得准确试验结果，过滤是样品制备的一个关键步骤。过滤的目的是为了除去溶出液中未溶解的药物和辅料。如果不把未溶解的药物和辅料从样品溶液中
除去，那么未溶解的药物颗粒将会继续溶解使试验结果出现偏差，因此，如果取样管中没有过滤器，应立即对溶出度样品进行过滤。
Filtration also removes insolubleexcipients that may otherwise interfere with the analytical finish. Selectionof the proper filter material is important and should be accomplished, andexperimentally justified, early in the development of the dissolutionprocedure. Important characteristics to consider when choosing a filtermaterial are type, filter size, and pore size. The filter that is selectedbased on evaluation during the early stages of dissolution procedure developmentmay need to be reconsidered at a later time point. Requalification has to beconsidered after a change in composition of the drug product or changes in thequality of the ingredients (e.g. particle size of microcrystalline cellulose).
过滤也可除去可能会干扰分析测定的不溶性辅料。选择适当的过滤材料是非常重要，应该在早期溶出方法开发的过程中通过实验确定和完成。在选择滤膜时有必要重点考虑滤膜的材料、型号和孔径大小。通常对早期阶段溶出方法开发过程的评价选择过滤器，但在后期试验中如果制剂成分改变或组成成分质量变化可能需要重新考虑过滤器，（例如：微晶纤维素粒径的改变）。
Examples of filters used in dissolutiontesting can be cannula filters, filter disks or frits, filter tips, or syringefilters. The filter material has to be compatible with the media and the drug.Common pore sizes range from 0.20 to 70 mm, however, filters of other poresizes can be used as needed. If the drug substance particle size is very small(e.g., micronized or nanoparticles), it can be challenging to find a filterpore size that excludes these small particles.
用于溶出试验的过滤器有管路过滤器、过滤盘或玻璃过滤器、滤头或针头式过滤器。过滤材料必须与介质和药物相适合。常见孔径大小范围：0.20～70μm，如果需要也可使用其他孔径大小的过滤器。如果原料药的粒度很小（例如，微分化颗粒或纳米颗粒），找到一个合适的过滤器过滤这些小颗粒至今仍具有挑战性。 Adsorption of the drug(s) by the filtermay occur and needs to be evaluated. Filter materials will interact withdissolution media to affect the recovery of the individual solutes and must beconsidered on a case-by-case basis. Different filter materials exhibitdifferent drug-binding properties. Percentage of drug loss from the filtratedue to binding may be dependent on the drug concentration. Therefore theadsorptive interference should be evaluated on sample solutions at differentconcentrations bracketing the expected concentration range. Where the drugadsorption is saturable, discarding an initial volume of filtrate may allow thecollection of a subsequent solution that approaches the original solutionconcentration. Alternative filter materials that minimize adsorptiveinterference can usually be found. Prewetting of the filter with the medium maybe necessary. In addition, it is important that leachables from the filter
