老王八Gelatin, in the prence of certain compounds and/or in certain storage conditions, including but not restricted to high humidity and temperature, may prent cross-linking.
A pellicle may form on the external and/or internal surface of the gelatin capsule shell or on the dosage form that prevents the drug from being relead during dissolution testing (e more information in Capsules—Dissolution Testing and Related Quality Attributes <1094>).
明胶，存在于某一处方和/或某一储存条件下，如：高温高湿，可能存在明胶交联结合作用。在胶囊壳或其他剂型的外外表和/或内外表形成一层膜阻止溶出试验过程中药物的释放〔见胶囊-溶出度检测和相关质量属性<1094>〕。
N OTE— All references to a chapter above <1000> are for information purpos only, for u as a helpful resource. The chapters are not mandatory unless explicitly called out for this application.
注-超过<1000>章节的所有引用应用的目的仅为提供参考信息。这些章节是非强制的，除非另有规定。
Dissolution Medium with pH ≤4.0 pH ≤4.0的溶出介质
Enzyme: Pepsin, activity determined by the procedure in purified pepsin, in the Reagent Specificatio
ns ction
酶：胃蛋白酶，活性视试剂规格局部中的胃蛋白酶提纯过程而定。
Amount: A quantity of pepsin that results in an activity of NMT 750,000 Units/L of dissolution medium
数量：一些胃蛋白酶对溶出介质提供NMT 750,000 单位/L的生物活性。Dissolution Medium with pH >4.0 and <6.8 pH >4.0 和<6.8的溶出介质
Enzyme: Papain, activity determined by the Assay test in the monograph for Papain; or bromelain, activity determined by the procedure in bromelain, in the Reagent Specifications ction
降血压都有哪些药酶：木瓜蛋白酶，活性视木瓜蛋白酶专论中的分析测试而定；或菠萝蛋白酶，活性视试剂规格局部中的菠萝蛋白酶生产过程而定。
Amount: A quantity of papain that results in an activity of NMT 550,000 Units/L of dissolution medium, or a quantity of bromelain that results in an activity of NMT 30 gelatin-digesting units (GDU)/L of dissolution medium
薄皇后数量：一些木瓜蛋白酶对溶出介质提供NMT 550,000 单位/L的生物活性；一些菠萝蛋白酶对溶出介质提供NMT 30明胶消化单位/L的生物活性。
Dissolution Medium with pH ≥6.8pH ≥6.8的溶出介质
Enzyme: Pancreatin, protea activity determined by the procedure in Assay for protea activity (Cain digestive power) in the monograph for Pancreatin
酶：胰液素，蛋白酶活性视胰液素专论中的蛋白酶活性〔酪蛋白消化能力〕分析中的生产过程而定。
Amount: A quantity of pancreatin that results in a protea activity of NMT 2000 Units/L of dissolution medium
数量：一些胰液素对溶出介质提供NMT 550,000 单位/L的蛋白酶活性。
Dissolution Medium Containing Surfactant or Other Ingredients Known to Denature the Enzyme含有外表活性剂或其他成分变性酶的溶出介质自编现代诗
If the dissolution medium contains surfactant or other ingredients that are known to denature the enzyme ud, a pretreatment step in the dissolution testing of the dosage form may be applied. This pretreatment step is done using the specified dissolution medium without the surfactant or the ingredient and with the addition of the appropriate amount of enzyme according to the medium pH. The amount of enzyme added is appropriate to the volume of dissolution medium ud in the pretrea
tment. To achieve the specified medium volume for the final dissolution testing, the pretreatment step may be conducted with a smaller volume of medium without the ingredient such that the final volume is obtained when the ingredient is added at the end of the pretreatment step. All of the other conditions of the test (apparatus, rotation, or flow rate) should remain as described in the method or monograph. Typically, the duration of the pretreatment step is NMT 15 min. The required pretreatment time should be evaluated on a ca-by-ca basis and should be scientifically justified. This time should be included in the total time of the test. As an example, if the total time of the test is 45 min and 15 min are ud in the pretreatment step, the test will continue for 30 min after the addition of the ingredient.
如果溶出介质中添加了外表活性剂或其他成分的变性酶，那么此溶出实验就要把预处理步骤考虑进去。预处理过程就是是根据溶出介质的pH来确定参加酶的量，此处的溶出介质不含有外表活性剂和原料。酶参加NMT 15 min。所需的预处理时间应该根据具体案例具体分析，且应该科学、合理。预处理时间应该包含在实验的总时间里。例如，如果实验的总时间为45min，预处理时间为15min，那么参加原料后实验还要继续进行30min。
USP Reference Standards 〈11〉—USP Prednisone Tablets RS.
USP参考标准<11>-USP强的松片RS。
APPARATUS仪器
Apparatus 1 (Basket Apparatus)第1法〔篮法〕
The asmbly consists of the following: a vesl, which may be covered, and made of glass or other inert, transparent material;1 a motor; a metallic drive shaft; and a cylindrical basket. The vesl is partially immerd in a suitable water bath of any convenient size or heated by a suitable device, such as a heating jacket. The water bath or heating device permits holding the temperature inside the vesl at 37 ± 0.5° during the test and keeps the bath fluid in constant, smooth motion. No part of the asmbly, including the environment in which the asmbly is placed, contributes significant motion, agitation, or vibration beyond that due to the smoothly rotating, stirring element. An apparatus that permits obrvation of the specimen and of the stirring element during the test is preferable. The vesl is cylindrical, with a hemispherical bottom and with one of the following dimensions and capacities: for a nominal capacity of 1 L, the height is 160–210 mm, and its inside diameter is 98–106 mm; for a nominal capacity of 2 L, the height is 280–300 mm, and its inside diameter is 98–106 mm; and for a nominal capacity of 4 L, the height is 280–300 mm, and its inside diameter is 145–
155 mm. Its sides are flanged at the top. A fitted cover may be ud to retard evaporation.2 The shaft is positioned so that its axis is NMT 2 mm at any point from the vertical axis of the vesl and rotates smoothly and without significant wobble that could affect the results. A speed-regulating device is ud that allows the shaft rotation speed to be lected and maintained at the specified rate given in the individual monograph within ±4%.
设备由以下局部组成：有盖或无盖的溶出杯，由玻璃或其他惰性的透明材料1制成；马达；转轴；转篮。溶出杯局部浸没在适宜大小的水浴中，或者由适宜的装置加热，例如电热套。水浴或加热装置需能在测试过程中将杯内温度保持在37±0.5℃，并且容许杯内液体持续、平缓的流动。整个仪器包括周围的环境，除了平稳转动的搅拌部件，不得有明显的运动，搅动或振动。仪器最好能允许在检测过程中能够观察到检品和搅拌部件。溶出杯为圆柱形，底部为半球形，尺寸和容积如下：名义容积1L的，高160-210mm，内径98-106mm；名义容积2L的，高280-300mm，内径98-106mm；名义容积4L的，高280-300mm，内径145-155mm。内壁顶部有缘。可以使用适宜的盖子减缓溶剂蒸发2。转轴与溶出杯的纵轴在任意部位不得相差差过2mm，转动平滑，无明显摇晃以至于影响检测结果。速度调节装置控制转轴的转速，并可维持在各论中规定值的±4%范围内。Shaft and basket components of the stirring element are fabricated of stainless steel, type 316, or other inert material, to the specifications shown in Figure 1. A basket having a gold coating of about 0.0001 inch (2.5 µm) thick
may be ud. A dosage unit is placed in a dry basket at the beginning of each test. The distance between the inside bottom of the vesl and the bottom of the basket is maintained at 25 ± 2 mm during the test.
转轴和篮筐组件由3161所示。可使用镀金厚度0.0001英寸〔2.5μm〕的篮筐。开始检测时，将一剂药品至于枯燥的篮筐中。在测试过程中，溶出杯底部到篮筐底部的距离应保持在25±2mm。
Figure 1. Basket stirring element.
图1. 转篮组成
Apparatus 2 (Paddle Apparatus)第2法〔桨法〕
U the asmbly from Apparatus 1, except that a paddle formed from a blade and a shaft is ud as the stirring element. The shaft is positioned so that its axis is NMT 2 mm from the vertical axis of the vesl at any point and rotates smoothly without significant wobble that could affect the results. The vertical center line of the blade pass through the axis of the shaft so that the bottom of the blade is flush with the bottom of the shaft. The paddle conforms to the specifications shown in Figure 2. The distance of 25 ± 2 mm between the bottom of the blade and the inside bottom of the vesl is
maintained during the test. The metallic or suitably inert, rigid blade and shaft compo a single entity. A suitable two-part, detachable design may be ud, provided that the asmbly remains firmly engaged during the test. The paddle blade and shaft may be coated with a suitable coating so as to make both of them inert. The dosage unit is allowed to sink to the bottom of the vesl before rotation of the blade is started. A small, loo piece of nonreactive material, such as NMT a few turns of wire helix, may
be attached to dosage units that would otherwi float. An alternative sinker device is shown in Figure 2a. Other validated sinker devices may be ud.
使用第1法中的设备，除了使用一个由叶片和转轴组成的桨作为搅拌单元。转轴与溶出杯的纵轴在任意部位不得相差差过2mm，转动平滑，无明显摇晃以至于影响检测结果。叶片的垂直中性线穿过转轴的轴线，叶片的下缘与转轴底部平齐。桨的尺寸应符合图2中的规定。在测试过程中，叶片底部与溶出杯底部的距离应保持在25±2mm。金属或硬质的叶片和转轴应是一个整体。两局部组合的设计也可以使用，只要组件在检测过程中牢固固定在一起。可以在桨叶和转轴上涂布适宜的涂层以使其为惰性。在桨叶开始旋转前，将一剂药品沉至溶出杯底。如果药剂浮在页面上，可以在其上附着一个惰性，松弛的小部件，例如几圈线圈，使其漂浮。图2是一种可替代使用的沉子。其他经验证的沉子也可以使用。
Figure 2. Paddle stirring element.
图2. 搅拌桨组成
Figure 2a. Alternative sinker. All dimensions are expresd in mm.
图2a. 可选的沉降篮〔单位均为mm〕
Apparatus 3 (Reciprocating Cylinder)第3法〔往复圆筒法〕
NOT ACCEPTED BY THE JAPANESE PHARMACOPOEIA日本药典未收录
脑神经核The asmbly consists of a t of cylindrical, flat-bottomed glass vesls; a t of glass reciprocating cylinders; inert fittings (stainless steel type 316 or other suitable material), and screens that are made of suitable nonsorbing and nonreactive material and that are designed to fit the tops and bottoms of the reciprocating cylinders; and a motor and drive asmbly to reciprocate the cylinders vertically inside the vesls; if desired, index the reciprocating cylinders horizontally to a different row of vesls. The vesls are partially immerd in a suitable water bath of any convenient size that permits holding the temperature at 37 ± 0.5° during the test. No part of the asmbly, including the environment in which the asmbly is placed, contributes significant motion, agitation, or vibratio
n beyond that due to the smooth, vertically reciprocating cylinder. A device is ud that allows the reciprocation rate to be lected and maintained at the specified dip rate given in the individual monograph within ±5%. An apparatus that permits obrvation of the specimens and reciprocating cylinders is preferable. The vesls are provided with evaporation caps that remain in place for the duration of the test. The components conform to the dimensions shown in Figure 3, unless otherwi specified in the individual monograph.
乱爱家庭所用设备包含一套圆柱形平底玻璃杯；一套玻璃往复圆筒；惰性配件〔316不反响材料制成的筛网，挡在往复圆筒的上下两端；一套马达和传动装置，将圆筒在玻璃杯中垂直往复运动，如果需要，也可以将往复圆筒平行移至另一行玻璃杯中。玻璃杯局部浸没在适宜尺寸的水浴中，水浴温度保持在37±0.5℃。仪器的任何部件，以及仪器所处的环境，都不应当引起明显的移动，搅动，振动，除了平滑的垂直往复运动的圆筒。使用设备维持往复速度在各论中所规定值的±5%范围内。仪器最好可以在检测过程中观察到样品和往复圆筒。玻璃杯配有蒸发帽，在检测中一直盖在玻璃杯上。除另有规定外，各局部的尺寸如图3所示。
Figure 3. Apparatus 3 (reciprocating cylinder).
图3. 图3 第3法〔往复圆筒法〕设备
使用拼音Apparatus 4 (Flow-Through Cell)第4法〔流通池法〕
The asmbly consists of a rervoir and a pump for the Dissolution medium; a flow-through cell; and a water bath that maintains the Dissolution medium at 37 ± 0.5°. U the specified cell size as given in the individual monograph.
所用设备包含一个溶出介质的容器和相应的泵，一个流通池和水浴。水浴将溶出介质保持在37±0.5℃。使用各论中规定的尺寸。
The pump forces the Dissolution medium upward through the flow-through cell. The pump has a delivery range between 240 and 960 mL/h, with standard flow rates of 4, 8, and 16 mL/min. It must deliver a constant flow (±5% of the nominal flow rate); the flow profile is sinusoidal with a pulsation of 120 ± 10 puls/min. A pump without pulsation may also be ud. Dissolution test procedures using a flow-through cell must be characterized with respect to rate and any pulsation.
泵将溶出介质推动，向上通过流通池。泵的传输能力在240到960mL每小时之间，标准速率为4，8，16mL每分钟。泵的流速必须均匀〔名义流量的±5%以内〕。泵的流量特性曲线应为正弦波，脉冲为每分钟120 ± 10 冲。无脉冲泵也可以使用。使用流通池法的溶出度测试必须对应特定的流速和脉冲。
The flow-through cell (e Figure 4 and Figure 5), of transparent and inert material, is mounted vertically with a filter system (specified in the individual monograph) that prevents escape of undissolved particles from the top of the cell; standard cell diameters are 12 and 22.6 mm; the bottom cone is usually filled with small glass beads of about 1-mm diameter with one bead of about 5 mm, positioned at the apex to protect the fluid entry tube; and a tablet holder (e Figure 4 and Figure 5) is available for positioning of special dosage forms, e.g., inlay tablets. The cell is immerd in a water bath, and the temperature is maintained at 37 ± 0.5°.
由透明且惰性材料制成的流通池〔见图4和图5〕垂直安放，配有过滤系统〔在各论中规定〕以防止未溶解的颗粒从流通池顶部逸出。标准的流通池直径为12和22.6mm。底部的锥形通常填有直径约1mm的小玻璃珠，其中一颗约5mm大的玻璃珠置于顶点处，以保护液体输入管。流通池配有药片架〔见图4和图5〕一满足特殊制剂的需要，如泡腾片。流通池浸没在37±0.5℃的水浴中。
Figure 4. Apparatus 4: large cell for tablets and capsules (top); tablet holder for the large cell (bottom). (All measurements are expresd in mm unless noted otherwi.)
书香满校园图4.第4法设备，盛装片剂和胶囊的大流通池〔上〕，大药片架〔下〕。〔除另有说明，所有尺寸单位为mm。〕Figure 5. Apparatus 4: small cell for tablets and capsules (top); tablet holder for the small cell (bottom). (All measurements are expresd in mm unless noted otherwi.)
图5 第4法设备，盛装片剂和胶囊的小流通池〔上〕，小药片架〔下〕。〔除另有说明，所有尺寸单位为mm。〕
