《溶出度实验的开发和验证讲解》由会员分享，可在线阅读，更多相关《溶出度实验的开发和验证讲解（128页珍藏版）》请在金锄头文库上搜索。
1、 THE DISSOLUTION PROCEDURE: DEVELOPMENT AND VALIDATIONINTRODUCTIONPurpose 目的The dissolution procedure: development and validation provides a comprehensive approach covering items to consider for developing and validating dissolution procedures and the accompanying analytical procedures. It addresses
2、 the use of automation throughout the test and provides guidance and criteria for validation. It also addresses the treatment of the data generated and the interpretation of acceptance criteria for immediate- and modified-release solid oral dosage forms.溶出度试验的开发和验证目的是为溶出度的测定提供了全面的开发和验证的方法以及相应的分析技术。本
3、指导原则贯穿溶出度测定的全部过程，并对方法验证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产生的数据和接受标准进行说明。Scope 范围Chapter addresses the development and validation of dissolution procedures, with a focus on solid oral dosage forms. Many of the concepts presented, however, may be applicable to other dosage forms and routes of administration.
4、 General recommendations are given with the understanding that modificaions of the apparatus and procedures as given in USP general 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部分在USP通则中给出了合理的说明。The organization of follows the sequence of actions often p
5、erformed in the development and validation of a dissolution test. The sections appear in the following sequence.在进行溶解度实验的开发和验证时，常遵循指导原则，具体内容如下：1. PRELIMINARY ASSESSMENT (FOR EARLY STAGES OF PRODUCTDEVELOPMENT/DISSOLUTION METHOD DEVELOPMENT) 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 Compatibil
6、ity 滤膜相容性研究1.2 Determining Solubility and Stability of DrugSubstance in Various Media 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 溶出介质和体积选择1.4 Choosing an Apparatus 溶出设备选择（桨法和篮法以及其他方法）2. METHOD DEVELOPMENT 方法开发2.1 Deaeration 脱气2.2 Sinkers 沉降篮2.3 Agitation 转速2.4 Study Design 研究设计2.4.1 Time
7、 Points 取样时间点2.4.2 Observations 观察2.4.3 Sampling 取样2.4.4 Cleaning 清洗2.5 Data Handling 数据处理2.6 Dissolution Procedure Assessment 溶出方法评估3. ANALYTICAL FINISH 完成分析3.1 Sample Processing 样品处理3.2 Filters 过滤3.3 Centrifugation 离心3.4 Analytical Procedure 分析方法3.5 Spectrophotometric Analysis 光谱分析3.6 HPLC4. AUTOM
8、ATION 自动化4.1 Medium Preparation 介质的配制4.2 Sample Introduction and Timing 定时进样4.3 Sampling and Filtration 取样和过滤4.4 Cleaning 清洗4.5 Operating Software and Computation of Results 操作软件和计算的结果5. VALIDATION 验证5.1 Specificity/Placebo Interference 专属性/安慰剂（辅料）干扰5.2 Linearity and Range 线性和范围5.3 Accuracy/Recovery
9、 准确度/回收率5.4 Precision 精密度5.4.1 REPEATABILITY OF ANALYSIS 重复性5.4.2 INTERMEDIATE PRECISION/RUGGEDNESS 中间精密度/耐用性5.4.3 REPRODUCIBILITY 重现性5.5 Robustness 耐用性5.6 Stability of Standard and Sample Solutions 样品溶液和标准溶液的稳定性5.7 Considerations for Automation 自动操作注意事项6. ACCEPTANCE CRITERIA 可接受标准6.1 Immediate-Rele
10、ase Dosage Forms 速释剂型6.2 Delayed-Release Dosage Forms 延迟释放剂型6.3 Extended-Release Dosage Forms 延长释放剂型6.4 Multiple Dissolution Tests 多个溶解度试验6.5 Interpretation of Dissolution Results 溶出结果说明6.5.1 IMMEDIATE-RELEASE DOSAGE FORMS 即时释放剂型6.5.2 DELAYED-RELEASE DOSAGE FORMS 延迟释放剂型6.5.3 EXTENDED-RELEASE DOSAGE
11、FORMS 延长释放剂型1. PRELIMINARY ASSESSMENT (FOR EARLY STAGES OF PRODUCT DEVELOPMENT/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）Before method development can begin, it is important to characterize the molecule so that the filter, medium, volume of medium, and apparatus can be chosen prop
12、erly in order to evaluate the performance of the dosage form.在溶出方法开发之前，了解颗粒的性质是非常重要的，以便对用以评估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恰当的筛选。1.1 Performing Filter Compatibility1.1 滤膜相容性研究Filtration is a key sample-preparation step in achieving accurate test results. The purpose of filtration is to remove undissolv
13、ed drug and excipients from the withdrawn solution. If not removed from the sample solution, particles of the drug will continue to dissolve and can bias the results. Therefore, filtering the dissolution samples is usually necessary and should be done immediately if the filter is not positioned on t
14、he 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，对溶出液进行过滤通常是必须的，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 insoluble excipients that may otherwise interfere with the analytical finish. Selection of the proper filter material is imp
15、ortant and should be accomplished, and experimentally justified, early in the development of the dissolution procedure. Important characteristics to consider when choosing a filter material are type, size, and pore size. The filter that is selected based on evaluation during the early stages of dissolution procedure development may need to be reconsidered at a later time point. Requalification has to be considered after a change in composition of the drug product or changes in the quality of the ingredients (e.g. particle size of microcrystalline cellulose).过滤也
