口服固体制剂通则比较

nullnullImpurity 杂质Content uniformity 含量均匀度 Uniformity of Dosage Unite 单位制剂均匀度郭建芳（Janie ）IMPURITIES 杂质IMPURITIES 杂质 郭建芳（Janie ） December 2008nullCONTENT 内容 财务内部控制制度的内容财务内部控制制度的内容人员招聘与配置的内容项目成本控制的内容消防安全演练内容 nullREFERENCEDEFINITION of IMPURITY　杂质的定义DEFINITION of IMPURITY　杂质的定义ChP.杂质：影响药品纯度的物质。 在药品质量 标准 excel标准偏差excel标准偏差函数exl标准差函数国标检验抽样标准表免费下载红头文件格式标准下载 中的杂质：在按照国家有关药品监督管理部门依法审查批准的规定工艺和规定原辅料生产的药品中，由其生产工艺或原辅料带入的杂质，或经稳定性试验确证的在贮存过程中产生的降解产物。 不包括：1.变更生产工艺or原辅料产生的新杂质。 2.渗入或污染的外来物质。 Ordinary impurities : those species in drug substances and/or drug products that have no significant, undesirable biological activity in the amounts present.〈466〉 一般杂质：在现剂量药物（或其制剂）中的无明显不良生物学活性的物质。 USPEP杂质：药用物质里面任何非药物的化学实体。DEFINITION of Related Substances　 有关物质的定义DEFINITION of Related Substances　 有关物质的定义ChP.有关物质：包括化学反应的前体、中间体、副产物和降解产物等。 Related Substances— Related substances are structurally related to a drug substance. 有关物质—有关物质与药物有结构相关性。 These substances may be (a) identified or unidentified impurities arising from synthesis manufacturing process such as intermediates or by-products and do not increase on storage or identified or unidentified degradation products that result from drug substance or drug product manufacturing processes or arise during storage of a material. USPEP有关物质：个论中用于有机杂质一般检验的标题。See 〈5.10〉 Other Definitions其他定义（已知杂质、 特定杂质）Other Definitions其他定义（已知杂质、 特定杂质） Identified Impurities and Identified Degradation Products— Impurities or degradation products for which structural characterizations have been achieved. Specified Impurities and Specified Degradation Products— Previously referred to as Signal Impurities, specified impurities or specified degradation products are impurities or degradation products that are individually listed and limited with specific acceptance criteria in individual monographs as applicable. Specified impurities or specified degradation products can be identified or unidentified. 〈1086〉 USPEPOther Definitions其他定义（共存物质）Other Definitions其他定义（共存物质）Concomitant components defined as species characteristic of many drug substances that are not considered to be impurities in the Pharmacopeial sense. Examples of concomitant components are geometric and optical isomers (or racemates) and antibiotics that are mixtures. Any component that can be considered a toxic impurity because of significant undesirable biological effect is not considered to be a concomitant component. 共存物质：很多药物的特殊种类，在药典意义上不认为是杂质。共存物质如几何异构体，旋光异构体（或外消旋物）或者是多组分抗生素等。（有不良生物学活性的毒性物质除外） 无定义。（共存异构体和抗生素多组分一般不作为杂质检查项目，必要时，在质量标准中规定其比例，共存物质是毒性杂质时，不再认为是共存物质） 无相关定义。 USPEPChP.Other Definitions其他定义Other Definitions其他定义Other Impurities其他杂质— Official substances may be obtained from more than one process, and thus may contain impurities not considered during preparation of monograph assays or tests. 〈Tests and Assays 〉 USPForeign Substances 外来物质(Extraneous Contaminants)— Foreign substances (extraneous contaminants), which are introduced by contamination or adulteration, are not consequences of the synthesis or preparation of compendial articles and thus cannot be anticipated when monograph tests and assays are selected. <1086>Inorganic Impurities无机杂质— Inorganic impurities can result from the manufacturing process (e.g., residual metals, inorganic salts, filter aids, etc.). Process Contaminants过程污染物— Process contaminants are identified or unidentified substances (excluding related substances and water), including reagents, catalysts, other inorganic impurities (e.g., heavy metals, chloride, or sulfate); and may also include foreign substances (extraneous contaminants). These contaminants may be introduced during manufacturing or handling procedures. Toxic Impurities毒性杂质— Toxic impurities have significant undesirable biological activity, even as minor components, and require individual identification and quantification by specific tests. Other Definitions其他定义Other Definitions其他定义EP 其他可检测杂质 See 〈5.10〉潜在杂质 See 〈5.10〉null ANALISIS METHOD药典中杂质检测 方法 快递客服问题件处理详细方法山木方法pdf计算方法pdf华与华方法下载八字理论方法下载 要求： 专属、灵敏 尽量使用现代分离 分析 定性数据统计分析pdf销售业绩分析模板建筑结构震害分析销售进度分析表京东商城竞争战略分析 手段，使主成分与杂质和降解物质均能分开 有机杂质：化学法、光谱法、色谱法。 其中常用的有HPLC、TLC、GC、CE（毛细管电泳）。 其中USP〈466〉的典型方法：TLC法。null ANALISIS METHOD药典中杂质检测方法无机杂质： 重金属的检查：重金属限度检查法（如砷盐检查法）、原子分光光度法、比色法等。 不挥发性无机杂质：炙灼残渣法等。 其他方法：如离子色谱法、电感耦合等发射光谱-质谱（ICP-MS） nullLimited 杂质限度null2034-1EP2034 limitsnull 药典中的杂质null 残留溶剂定义null 残留溶剂分类null 残留溶剂的分类（ICH、EP、USP）null 残留溶剂分析方法CLASS1CLASS1Table 1. Class 1 Residual Solvents (solvents that should be avoided)   中国药典内容null CLASS2EP中为 Dichloromethanenull CLASS3中国药典、美国药典和欧洲药典对残留溶剂的分级和各个级别残留溶剂的种类以及对相应残留溶剂的限度要求是相同的！null Other Residual Solvents Table 4. Other Residual Solvents (for which no adequate toxicological data was found) null残留溶剂的鉴别、控制和定量 EP〈5.4〉附录附录1 LIST OF THE SOLVENTS INCLUDED IN THE GUIDELINE(包括化学名称，结构式和相应的类别) 附录2 ADDITIONAL BACKGROUND 附录3 METHODS FOR ESTABLISHING EXPOSURE LIMITSUSP<467> OTHER ANALYTICAL PROCEDURES (used where specified in the individual monographs ) METHOD I METHOD IV METHOD V METHOD VInull残留溶剂的鉴别、控制和定量 USP区别于ChP.和EP：在〈467〉中规定了残留溶剂 测定的具体方法和操作步骤。 即该项下〈IDENTIFICATION, CONTROL, AND QUANTIFICATION OF RESIDUAL SOLVENTS 〉The following procedures are useful to identify and quantify residual solvents when the information regarding which solvents are likely to be present in the material is not available. When the information about the presence of specific residual solvents is available, only Procedure C is needed to quantify the amount of residual solvents present. 该程序用于没有药物中可能存在的残留溶剂的相关信息时,对残留溶剂进行鉴别和确认。（程序A—程序B—程序C） 当有某种残留溶剂存在的信息时，只需要程序C进行存在残留溶剂的定量USP中包括：水溶性残留物、水不溶性残留物的检测方法。CONTENT UNIFORMITY & UNIFORMITY OF DOSAGE UNITE 含量均匀度 单位制剂均匀度CONTENT UNIFORMITY & UNIFORMITY OF DOSAGE UNITE 含量均匀度 单位制剂均匀度 郭建芳（Janie ） December 2008nullCONTENT 内容含量均匀度定义含量均匀度定义SCOPE 范围SCOPE 范围ChP.EPEP Usp Table 1 Usp Table 1 续（表1）USP续（表1）USPnullCU检查方法和可接受标准1、中国药典测定方法： 10片测定——计算相对于标示量的含量X——求X的平均值，标准差S，标示量和均值的差的绝对值A ——评判！ 评判方法：A+1.80S≤15.0,供试品含量均匀度符合规定； 否则不符合规定。 A+1.80S＞15.0，A+S≤15.0,另取20片复试。计算30片均值，标准差S，标示量和均值的差的绝对值A ，评判！ 评判方法：A+1.45S≤15.0,供试品含量均匀度符合规定；否则不符合规定。其他限度其他限度2. EP2. EPnullnull3. USP uniformity of dosage units3. USP uniformity of dosage units 计算方法和评判标准：与EP相同！重量差异法（注：该法为单位制剂均匀度的测定方法之一）重量差异法（注：该法为单位制剂均匀度的测定方法之一）Usp，EP 选定30片——取10片分别称重——计算Xi，和W——评判！ 1, 可接受标准：与含量均匀度评判标准计算方法一致！AV=︱M-X均︱+ks，AV与L1%比较 评判方法：AV≤L1%,供试品含量均匀度符合规定；AV＞L1%，取剩余20片复试。计算30片AV。评判！ 评判方法：AV≤L1%,无单个剂量含量小于[1-(0.01)(L2)] M或者大于[1 + (0.01)(L2)] M则合格。L1，L2一般为15.0和25.0，除非各论中有特别规定。CHP: 在各个剂型中分别规定！最低装量最低装量中国药典，附录ⅩF《最低装量检查法》 适用范围：固体、半固体和液体制剂。（除制剂通则中规定检查重量差异的制剂及放射性药物外） 检查法：重量法、容量法。USP<755> MINIMUM FILL 适合乳膏，凝胶，凝胶剂、洗液、软膏、贴剂、粉末和喷雾剂，包括加压和未加压的包装在容器中的标示量不大于150g或者150ml的喷雾剂。 检查法：非喷雾剂检查法、喷雾剂检查法。最低装量限度最低装量限度ChP《最低装量检查法》 检查量：5剂量（50g or ml以上3剂量）。限度：USP<755> MINIMUM FILL 检查量：10剂量。限度：若有1个容器装量不符合规定，另取5个（或3个）复试，应全部符合规定。null 特别鸣谢！ 胡伟军 周良彬 特别鸣谢！ 胡伟军 周良彬