media containing surfactants or lipidsmay presentproblems. Carryover may occur for successive samples taken over amultipletime-point test, as well as at the beginning of a new test due to thecleaningsolution. This topic is discussed in section 4.4 Cleaning.
当后续样品受残留或先前取样条件的影响，可能会发生交叉污染；第一个样品或条件的影响传递到第二样品。在处理液体时，在样品溶液中先前液体的残留物可能污染后续样品溶液。溶出介质包含表面活性剂或脂质可能会存在一些问题。根据清洗方案在多个时间点测试和在开始新的检测以及连续采样都可能发生残留。这个问题将在4.4节清洁进行讨论。
Interaction of dissolved drugsubstancewith the sampling and transfer devices is an important consideration.Whenadsorption of the dissolved drug substance occurs, it most ofteninvolvessurfaces of the dissolution apparatus or sampling filters and
tubing. Adsorption may be pHdependent in the case ofcharged, dissolved drug substance. Adsorption of thedissolved drug to the partsof the sampling device should be assessed using atypical sample solution(dissolution sample from the product or
drug substance withformulation matrix) with knownconcentration. The typical design is across-validation with aliquots of thesame sample solution passing andbypassing the sampling device (including thesampling probe, filter, tubing,valves, and pump). There is no generalrecommendation that may give preferenceto any kind of material or equipmentconstruction (e.g., glass or specificpolymers). See section 5.7Considerationsfor Automation for more information.
溶解的原料药的取样和设备转移之间的相互作用是需要重点考虑的，当溶解的原料药发生吸附时，通常发生在溶解装置或抽样滤波器和管道的表面上。溶解的原料药在带有电荷时发生吸附可能是pH依赖性的。溶解的原料药到采样装置部件的吸附应当使用已知浓度的典型样品溶液进行评估（使用制剂或原料和辅料混合组分进行溶出的样品）。通常使用同一样品溶液分成两等份，设计一个交叉验证试验，分别通过和绕过取样装置（包括采样探头，过滤器，管道，阀门和泵）。有可能对任何种类的材料或设备结构（例如，玻璃或特定的聚合物）的优先选择不能给出建议。参见5.7自动化注意事项的详细信息。
In addition to the informationin section2.4.3 Sampling,connections of pumps and tubing may be sources of contaminationin automatedsystems. Interferences with the spectroscopic analyticalprocedures, which arecommonly
used for dissolution testing, are less of aconcern. However,interferences must be evaluated if the product underinvestigation containslow-dose metal salts, as do some dietary supplements.
除了在2.4.3取样部分的信息外,泵和管道的连接处可能是自动化系统污染的来源。在溶出测定时，光谱分析方法产生的干扰通常关注较少。但是，研究的制剂如果含有低剂量的金属盐，如做一些膳食补充剂必须对干扰进行评估。
Liquid transfer usually isundertaken viapolymeric tubing. Inert materials such aspolytetrafluoroethylene (PTFE)sometimes cannot be used because of their mechanicalproperties. Where flexibletubes are required, for example in peristaltic pumpsor for coiling in a smallradius, polypropylene (PP) or high-densitypolyethylene (HDPE) may be the preferredmaterials. Depending on the type ofpolymer and its crystallinity and density,leaching of constituents, mainlyplasticizers, may occur. Leachables caninterfere with the
analyticalprocedure. The concentration leached to the samplesolution usually depends onthe surface,the temperature, the exposure time, thehydrodynamic conditions,and the composition of the media.
液体转移通常是通过聚合物管进行。惰性材料如聚四氟乙烯（PTFE），因为它们的机械性能有时也无法使用。需要使用软管时，例如在蠕动泵或用于在小半径环绕，聚丙烯（PP）或高密度聚乙烯（HDPE）是优选的材料。取决于聚合物的类型、结晶度和密度、主要增塑剂，可能产生组分浸出。溶出物可能干扰分析测定。被过滤到样品溶液中的浓度通常取决于表面、温度、暴露时间、流体动力学条件和溶出介质的组成。 4.4 Cleaning 4.4 清洗
In addition to the informationin section2.4.4 Cleaning,automated systems have specific cleaning issues. For example,evaluation of theeffectiveness of purging and rinsing between sampling timesand within-runcondition of the tubing is recommended. Also it is important toevaluate thecleaning process between tests.
除了2.4.4清洁部分的信息，自动系统也有具体的清洁问题。例如，推荐在采样时间和管的批内运行条件评估清洗和冲洗的有效性。在试验之间评估清洁过程也是很重要的。
4.5 Operating Software andComputation ofResults 4.5操作软件和计算的结果
The software systems for dataevaluationand instrument operation must be validated as per 21 CFR 11 (17).
根据21 CFR11（17）仪器操作系统和数据评估软件必须进行验证。 4.6 Common Deviations from theCompendialProcedures That May Require Validation
4.6药典方法常见偏差需要进行验证
Some common areas of deviationfromcompendial procedures include the following:
? Sample introduction relativeto start ofspindle rotation ? Residence time andpositioning ofsampling probes ? Recirculated versusconsumptive sampling
? Sample volume replacement inconsumptivesampling. 药典方法的一些常见偏差包括： ?主轴开始旋转投入样品引起的偏差 ? 停留时间和采样探头位置 ?循环与消耗采样
?在消耗采样时取样体积更换。 5. VALIDATION 5.验证
Thevalidation topics described in this section are typical but not all-inclusiveand can be viewed in the context of Validation of Compendial Procedures <1225>,as well as the International Conference on Harmonization (ICH) document, Validationof Analytical Procedures (18). Validation for both parts of the dissolutionprocedure, the analytical finish and the dissolution step, willbediscussed in this section. The dissolution step is the release of the drug inthe dissolution medium and sampling. The analyticalfinish is defined insection 3. Analytical Finish. Validation of the analytical finish willevaluate the attributes, linearity andrange, precision, specificity,accuracy/recovery, robustness, and stability of the sample and standardsolutions. Validation of thedissolution step will include evaluation ofprecision and robustness of the dissolution sample preparation. Validation ofthe analyticalfinish is performed either using a standard solution orspiked placebo or by the method of standard addition (spikeddrugproduct as described in Accuracy in <1225>), as specified in thesections below. Validation of the dissolution step requiresthe use of awell-characterized dosage form (e.g., having tight content uniformity anduniform performance). Depending onthe parameter of interest, validationof the sample handling and analytical procedure can be performed in situ, e.g.,within thedissolution vessel. The validation parameters addressed andthe extent of
the validation may vary, depending on the phase ofdevelopmentor the intended use for the data.
本章节所涉及的验证是一些典型的验证，但不包括所有的验证，这些验证在
药典分析方法验证<1225>的上下文中和ICH指导原则分析方法验证。本章节讨论的溶出实验的验证包括溶出和分析两部分验证。溶出步骤是指药物在溶出介质中的释放和取样，分析方法的定义详见第3章节分析方法。分析方法的验证包括专属性、线性和范围、精密度、准确定/回收率、耐用性、对照品溶液和供试品溶液的稳定性。而溶出步骤的验证主要是对溶出样品制备的精密度和耐用性评估。分析方法验证一般使用标准溶液或者空白辅料溶液或通过下面章节中指定的标准加入法（按照<1225>准确度试验中描述的加入标准的药品）。溶出步骤的验证需要使用具有良好特性的产品（例如：具有良好的含量均匀度和溶出均一性）。根据关注的参数，在原来位置，比如在溶出仪里进行分析方法和样品处理的验证。验证参数处理和验证程度会有所不同，这取决于开发阶段或数据的使用目的。
The acceptance criteria are presented as guidelinesonly, and may differ for some products. Manufacturers should document theappropriate acceptance criteria for their products in pertinent StandardOperating Procedures (SOPs) or in validation protocols.Other considerations maybe important for special dosage forms. Validation studies should be performedacross the range of profile time points. For products containing more than asingle active ingredient, the dissolution procedure needs to be validatedfor each active ingredient. It is expected that investigations into
filtersuitability and the potential for glass adsorption will have been undertakenalready (see 1.1 Performing Filter Compatibility). Validation of theseassessments may occur during spiked recovery experiments.
本章节的验证标准仅作为指导，对有些产品可能有所不同。生产厂家应该在相关的标准操作规程（SOP）中或在验证方案中对制剂产品提供合适的可接受标准。对特殊剂型的其他考虑也是重要的。所进行的验证研究应横跨溶出曲线时间点范围。对于复方或者多组分制剂，每一种活性成分的溶出方法均需要进行验证。过滤器的相容性以及玻璃器的潜在吸收已经进行研究（见1.1滤膜的选择和相容性），在加标回收率试验中将对这些评估进行验证。 5.1 Specificity/PlaceboInterference 5.1专属性/安慰剂（辅料）干扰
It isnecessary to demonstrate that the results are not unduly affected by
placeboconstituents, other active drugs, or degradants. The placebo consists of allthe excipients and coatings, with inks and capsule shells included ifappropriate, without the active ingredient. Placebo interference can beevaluated by using a spiked placebo that is prepared by weighing samples of theplacebo blend, dissolving or dispersing them in
dissolution medium atconcentrations that would be encountered during testing, and adding a knownamount of the drug in solution. It may be preferable to perform this experimentat 37°, comparing the solution to a standard solution at the concentrationexpected to be encountered during testing, by using the formula: Result = (AP/AS) × CS × (V/L) × 100 AP =absorbance of the placebo AS =absorbance of the standard
CS =concentration of the standard (mg/mL) V =volume of the medium (mL) L =label claim (mg)
证明安慰剂（空白辅料）成分、其他活性药物或降解产物并非影响试验结果是很有必要的。安慰剂是指除了活性成分以外的所有辅料和包衣材料，在适当的时候还包括油墨和胶囊壳。安慰剂的干扰可以使用加入标准的安慰剂进行评价，通过称取安慰剂的混合样品，将该混合样品溶解或分散在溶出介质中，制备的浓度为测试过程中使用的浓度，然后向溶液中加入一定量药物，优选在37℃试验条件进行这个试验，使用如下公式比较样品溶液和标准溶液在测试过程中预计浓度点的吸光度：
结果= (AP/AS)×Cs×(V/L)×100 AP为安慰剂的吸光度 AS为标准溶液的吸光度 Cs为标准溶液的浓度（mg/ml） V为溶出介质的体积（ml） L为标示量（mg）
Theinterference should not exceed 2%. Note that for extended-release products, aplacebo version of the finished dosage form may be more appropriate than
blendsbecause this placebo formulation will release the various excipients in amanner more nearly reflecting the product than will a simple blend of theexcipients. In this case, it may be appropriate to evaluate potentialinterference at multiple sampling points in the release profile, withworst-case interference expected at the later sampling points.
干扰不能超过2%。值得注意的是：缓释制剂，空白剂型可能比混合物更合适，因为空白剂型比各种辅料简单的混合物更能反映出不同辅料制剂的释放方式。在这种情况下，在多个取样点的释放曲线更适合评估潜在干扰，尤其是后面的取样点预计出现的最坏干扰。
The blank is the dissolution medium withoutdissolved sample, and it is treated in the same manner as the sample. Theeffect of the absorbance of the blank at the analytical wavelength should beevaluated. In most cases, the absorbance of the dissolution medium blank maynot exceed 1% of the standard solution at the
