.wd（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 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指导原那么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。本指导原那么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承受标准进展说明。Scope范围Chapter 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.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局部在USP通那么中给出了合理的说明。The organization of follows the sequence of actions often performed inthe development and validation of a dissolution test. The sections appear inthe following sequence.在进展溶解度实验的开发和验证时，常遵循指导原那么，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 Compatibility1.1滤膜相容性研究1.2 Determining Solubility and Stability of DrugSubstance in Various Media1.2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 Volume1.3溶出介质和体积选择1.4 Choosing an Apparatus1.4溶出设备选择桨法和篮法以及其他方法2. METHOD DEVELOPMENT2.方法开发2.1 Deaeration2.1脱气2.2 Sinkers2.2沉降篮2.3 Agitation2.3转速2.4 Study Design2.4研究设计2.4.1 TimePoints2.4.1取样时间点2.4.2 Observations2.4.2观察2.4.3 Sampling2.4.3取样2.4.4 Cleaning2.4.4清洗2.5 Data Handling2.5数据处理2.6 Dissolution Procedure Assessment2.6溶出方法评估3. ANALYTICAL FINISH3.完成分析3.1 Sample Processing3.1 样品处理3.2 Filters3.2 过滤3.3 Centrifugation3.3 离心3.4 Analytical Procedure3.4 分析方法3.5 Spectrophotometric Analysis3.5 光谱分析3.6 HPLC3.6HPLC法4. AUTOMATION4.自动化4.1 Medium Preparation4.1介质的配制4.2 Sample Introduction and Timing4.2定时进样4.3 Sampling and Filtration4.3取样和过滤4.4 Cleaning4.4 清洗4.5 Operating Software and Computation of Results4.5操作软件和计算的结果5. VALIDATION5.验证5.1 Specificity/Placebo Interference5.1专属性/抚慰剂辅料干扰5.2 Linearity and Range5.2线性和范围5.3 Accuracy/Recovery5.3准确度/回收率5.4 Precision5.4精细度5.4.1 REPEATABILITY OF ANALYSIS5.4.1重复性5.4.2 INTERMEDIATE PRECISION/RUGGEDNESS5.4.2中间精细度/耐用性5.4.3 REPRODUCIBILITY5.4.3重现性5.5 Robustness5.5耐用性5.6 Stability of Standard and Sample Solutions5.6样品溶液和标准溶液的稳定性5.7 Considerations for Automation5.7自动操作考前须知6. ACCEPTANCE CRITERIA6.可承受标准6.1 Immediate-Release Dosage Forms6.1速释剂型6.2 Delayed-Release Dosage Forms6.2延迟释放剂型6.3 Extended-Release Dosage Forms6.3延长释放剂型6.4 Multiple Dissolution Tests6.4多个溶解度试验6.5 Interpretation of Dissolution Results6.5溶出结果说明6.5.1 IMMEDIATE-RELEASE DOSAGE FORMS6.5.1即时释放剂型6.5.2 DELAYED-RELEASE DOSAGE FORMS6.5.2延迟释放剂型6.5.3 EXTENDED-RELEASE DOSAGE FORMS6.5.3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.在开场溶出方法开发之前，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展适当的筛选是非常重要的。1.1 Performing Filter Compatibility1.1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展过滤。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 prod