也有可能会减少可接触的表面积导致溶出率下降。气泡对难溶性药物的干扰最敏感；因此检验这些类型的产品时需要脱气。在<711>部分附录中描述了脱气方法。典型的脱气方法：加热、过滤和在短时间内抽真空。其他脱气方法和常规使用的脱气方法也是可用的。一旦确定一个合适的脱气方法，应该作为溶出方法的一部分记录下来。通过测量总溶解气体压力或通过测量水中溶解的气体浓度来评估脱气的程度。例如，使用USP的性能验证测试泼尼松龙片校正片发现水中氧浓度低于6毫克/升时，表明水已充分脱气。
Media containing surfactants usuallyare not deaerated because the process results in excessive foaming, and usuallythe effect of dissolved air on the dissolution process is mitigated by thereduced surface tension of the medium. Sometimes, deaerating the medium beforeadding surfactants can be effective.
含有表面活性剂的溶出介质由于脱气过程会产生过多气泡通常不容易脱气，通常采用减少溶出介质中的表面张力，来减轻溶解的空气对溶解过程产生的影响，有时，在加入表面活性剂之前对溶出介质进行脱气是有效的。
To determine whetherdeaeration of the medium is necessary, compare results from dissolution samplesrun in non-deaeratedmedium and medium deaerated using a compendial technique,as described above. If no effect of deaeration is detected, this experiment could serve asjustification that deaeration is not required in the future. If there is aneffect, however, then it isnecessary to carefully control this parameter, andit is prudent to characterize the robustness of the deaeration process.
Thedissolvedgas content of deaerated media under atmospheric pressure is unstable and willtend toward saturation. Manipulationsof the deaerated medium such as stirringor pouring can increase the rate at which atmospheric gases are redissolved. 确定溶出介质是否需要脱气是必要的，如上面所描述的，使用药典技术中的脱气方法，比较样品在脱气和未脱气的溶出介质中的溶出试验结果。如果检测结果表明脱气对溶出结果没有影响，该试验就可以作为不需要进行脱气的理由进行说明。如果脱气对试验结果有影响，那么有必要准确控制这个参数，详细描述脱气过程中耐受性特点。在大气压强下，脱气介质中溶解的气体量是不稳定的，会趋向饱和。比如搅拌或倾倒已脱气的介质可以增加气体的再溶解速率。 2.2 Sinkers 2.2沉降篮
Sinkersare often used to adjust the buoyancy of dosage forms that would otherwisefloat during testing with Apparatus 2. When sinkers are used, a detaileddescription of the sinker must be provided in the written procedure. It may beuseful to evaluate different sinker types, recognizing that sinkers cansignificantly influence the dissolution profile of a dosage unit. Whentransferring the procedure, the same sinkers should be used, or if a differentdesign is used, it should be shown to produce equivalent results. There
areseveral types of commercially available sinkers. In <711>, a harmonizedsinker is described in Figure 2a.
在使用仪器2进行测试时，沉降篮通常用于调节易于漂浮的剂型。当使用沉降蓝时，必须对沉降篮仪器进行详细描述。评估沉降篮的不同类型，同时要认识到沉降篮能够显著影响溶出曲线。当转移这个方法时，应使用相同的沉降篮，或者如果使用不同设计的沉降篮，应当证明两种不同的沉降篮产生的结果相同。有几种可用的商业类型的沉降篮。在<711>中图2a中统一对沉降篮进行了详细的描述。
A standard sinker can be made by using theappropriate length of wire and coiling it around a cylinder. For materials,use316 stainless steel wire, typically 0.032 inch/20 gauge, or other inertmaterial and wind the wire around cylinders of appropriatediameter (e.g., corkborers) for an appropriate number of turns to fit the capsule shell type. Sizesare shown in Table 2. Theends of the coil can be curved to retain thecapsule within the sinker when they are immersed. Because the ends of thewiremay be rough, they may need to be filed. If the sinker is handmade, thesinker material and construction procedure instructionsshould be documented(e.g., dimension, design, number of coils); if a commercial sinker is used, thevendor part numbershould be reported if available. 一个标准的沉降篮可以通过使用合适长度的金属丝围绕圆柱体卷绕制成。使用316不锈钢丝为材料，通常0.032英寸/20号，或其它惰性材料和缠绕适当直径的圆柱体（如，木塞穿孔器）和缸丝匝数量以适合胶囊壳的类型。表2中列出了尺寸。线圈的端部可以是弯曲的，以保持胶囊在沉降篮内浸润。因为金属丝的端部是粗糙的，他们可能需要修整。如果沉降篮是手工制作，应记录沉降篮的材料和结构（例如，尺寸，设计，线圈数）;如果用的是商业沉降篮，应当提供供应商零件号。
Table 2. WireSinkers Used With Common Capsule Shell Sizes
表2普通胶囊壳规格使用的沉降篮金属线尺寸
Although sinkers are typically used to keep thedosage form at the bottom of the vessel, they can also be used to keep dosageforms from sticking to the vessel (e.g., film-coated tablets). The sinkershould be appropriate to the dosage form; therefore,the same sinker size maynot be suitable for all dosage-form sizes. The sinker should not be too tightaround the dosage form because this may restrict interaction with the
medium.Conversely, if wrapped too loosely, the dosage form may escape soon after the testbegins. The sinker should be small enough that the capsule does not change
itsorientation within the sinker.Care should be taken when testing capsules thathave some cross-linking present, to keep the sticky shell from attaching to thevessel bottom. In this case, the harmonized sinker design provided in Figure2a of <711>will be advantageous.
虽然通常使用的沉降篮是为了保持剂型在容器底部，它们也能够使剂型不粘附在容器壁中（例如：薄膜包衣片）。沉降篮应适合于剂型。因此，相同大小的沉降篮可能不适合所有的剂型型号。沉降篮不应围绕剂型太紧或太松，太紧可能会限制剂型与介质的相互作用，太松剂型可能会逃脱。在测试开始后不久。沉降篮应该足够小使得胶囊在沉降篮内不能改变方向。胶囊存在交联时，试验时应小心，以保持胶囊壳不粘附在容器底部。在这种情况下，在<711>图2a中统一提供的沉降篮设计将是有利的。 2.3 Agitation 2.3转速
Forimmediate-release capsule or tablet formulations, Apparatus 1 (baskets) at 50–100 rpm or Apparatus 2 (paddles) at 50or 75rpm are used commonly. Other agitation speeds are acceptable with appropriatejustification. Rates outside 25–150 rpmfor both the paddle and the basket are usually not appropriatebecause of mixing inconsistencies that can be generated bystirring too slow ortoo fast. Agitation rates between 25 and 50 rpm are generally acceptable forsuspensions.
对于速释胶囊或片剂，一般采用仪器1（篮法）50～100 rpm，或者仪器2（桨法）50或75rpm。如果有合适的理由选择其他转速也是可以接受的。考虑到转速太慢或太快产生混合不一致，无论是篮法或者桨法，低于25 rpm或高于150 rpm的转速，均是不能接受的。对于混悬剂一般推荐转速25rpm～50rpm。 For dosage forms that exhibit coning(mounding) under the paddle at 50 rpm, the coning can be reduced by increasingthe paddle speed to 75 rpm, thus reducing the artifact and improving the data.If justified, 100 rpm may be used with Apparatus 2, especially forextended-release products. Decreasing or increasing the apparatus rotationspeed may be justified if to achieve an in-vitro–in-vivo correlation (IVIVC)the resulting profiles better reflect in vivo performance, or if the methodresults in better discrimination without adversely affecting method variability.
桨转速50rpm时，剂型在浆下存在圆锥（丘）状，将转速增加至75 rpm可以减少圆锥状，从而提高溶出数据。尤其是对于缓释制剂制剂，如果经过证明，也可以采用桨法100rpm转速。如果能够实现体内外相关性（IVIVC），使体外溶出曲线更好的反应体内溶出特性，或者在不影响方法差异性的情况下溶出结果具有更好的区分力，增加或减小仪器转速均是合理的。
Apparatus 3 (reciprocating cylinder)can be used at dip rates ranging from 5 to 30 dips/min. The hydrodynamics areinfluenced by the cylinder's reciprocating motion and
the resulting movement ofthe sample in the medium. The reciprocating motion of the cylinder and screenmay cause foaming if the medium contains surfactants. Addition of ananti-foaming agent such as simethicone or n-octanol may be useful foravoiding foaming from surfactants.
仪器3（往复缸）可用于浸率范围5～30 dips/分钟。气缸的往复运动影响流体力学和样品在介质中溶出结果。如果溶出介质中含有表面活性剂，在气缸和监视器的往复运动会引起起泡。加入消泡剂，如硅油或正辛醇，可避免表面活性剂产生的泡沫。
Apparatus 4(flow-through cell) is described in <711> with standard flow rates of 4, 8,and 16 mL/min. Other flow rates for Apparatus 4 can be used if justified and ifwithin the capacity of the pump to conform with the requirements in á711?. Agitationin Apparatus 4 is not only related to the pump speed but can also be affectedby cell diameter. At a set flow rate, as measured by volume, the 12-mm cellwill develop a greater linear fluid velocity than is achieved in the 22.6-mmcell. Apparatus 4 can be configured with the addition of glass beads in theentry cone of the flow-through cell (packed column) or without glass beads(open column).
仪器4 (流通池)在<711>中描述了标准流速4、8、16ml/min。如果经过验证并且在该泵的承受的能力范围内符合<711>的要求，仪器4也可以使用其他流速。在仪器4中搅动不仅影响泵的速度也影响孔直径。通过测定体积设定流速，12mm孔径比22.6mm孔径产生的线性流速要大。仪器4在流体单元的入口通过加入玻璃珠（填充柱）或者去掉玻璃珠（开放柱）进行配置。 2.4 Study Design 2.4 研究设计
Selectionof the agitation rate and other study design elements for the dosage form,whether immediate release or modified release, should conform to therequirements and specifications (i.e., apparatus, procedures, andinterpretation) given in <711>.
不管是速释制剂或者是缓控释制剂，对转速选择和剂型的其他研究设计，均应符合<711>规范要求（即仪器，方法和说明）。 2.4.1 TIME POINTS 2.4.1 取样时间点
For immediate-release dosage forms, theduration of the dissolution procedure is typically 30–60 min; in most cases, asingle time point specification is adequate for pharmacopeial purposes. Formethod development, however, a sufficient number of time points should beselected to adequately characterize the ascending and plateau phases of thedissolution curve. Industrial and regulatory concepts of product comparabilityand performance may require additional time points, which may also be
requiredfor product registration or approval. According to the
BiopharmaceuticsClassification System referred to in severalFDA Guidances, highly soluble,highly permeable drugs formulated into very rapidly dissolving products neednot be subjected to a profile comparison if they can be shown to release 85% ormore of the drug substance within 15 min. For these types of products, aone-point test or disintegration will suffice. However, most products do notfall into this category. Dissolution profiles of immediate-release productstypically show a gradual increase reaching 85%–100% at about 30–45 min. Thus,sufficient dissolution time points are chosen to characterize the performancefor most immediate-release products. For some products,including suspensions,useful information may be obtained from earlier points, e.g., 5–10 min. Forslower-dissolving products, time points later than 60 min may be useful.Dissolution test times for compendial tests are usually established on thebasis of an evaluation of the dissolution profile data.
对于速释制剂，溶出度测定时间通常为30～60 min；在大多数情况下，单点取样设计足够满足药典的控制要求。但是，对于方法的开发阶段，应选择足够多的时间点来充分表征溶出量增加和达到溶出平台的趋势。工业和法规概念对产品的相似性和产品性能进行研究需要增加取样时间点，产品的注册或批准同样需要。根据FDA指导原则中生物药剂学分类系统，高溶解性高渗透性药物（快速溶出药物），如果在15分钟内溶出度达到85%以上，可不再进行曲线考察，单点试验就足够了。然而，大多数产品不属于这一分类。速释制剂的溶出度通常呈逐渐增加趋势，一般在30～45分钟溶出达到85%～100%。因此，大多数速释制剂会选择充足的时间点来表征产品的溶出特性。对于一些产品，包括悬浮液，早期取样时间点获得的信息比较有用，例如，5，10分钟。对于溶出速度较慢的产品，60分钟后的时间点可能是有用的。药典中规定溶解度试验时间的确定通常是建立在对溶出曲线数据评估的基础之上。
The f2 similarityfactor may not be useful when more than 85% is dissolved at 15 min. If the f2similarity factor is to be used,multiple time points for the dissolution testare required, with at least two time points with mean percent dissolved(typically for n = 12) below 85% dissolved and only one point above 85% forboth products (16). Therefore, the addition of early time points may be useful.
f2相似因子不适用于15分钟溶出量大于85%的制剂。如果使用f2相似因子进行比较，需要进行多个时间点溶出度测定，至少两个取样时间点平均溶出值低于85%（一般是n=12）并且两组产品的溶出度值只有一个时间点大于85%。因此，在早期增加时间点检查是有必要的。
For testing anextended-release dosage form, at least three time points are chosen, to guardagainst dose dumping, to define the in vitro release profile, and to show thatessentially complete release (>80%) of the drug is achieved. Additionalsampling
