（原创）中美溶出仪机械确认指南原则对比

hongwei2000

编号	CFDA	FDA	点评
1	二、机械验证的测量工具    溶出仪的机械验证，应将待测部件置于正常溶出试验位置，由相关技术人员使用适宜的测量工具测量各项机械参数。    可采用单一测量工具（如倾角仪、同轴度测量工具、摆度表、深度表、转速计和温度计等），也可采用模块化集成测量工具。不论哪种测量工具，均应在检定合格周期内使用，并能够进行量值溯源。		对于设备而言，用“确认”这个词比“验证”这个词更恰当。
2	三、机械验证的周期    溶出仪在安装、移动或维修后都应对其进行机械验证。除另有规定外，通常每六个月对溶出仪进行一次机械验证。如果在试验过程中发现异常现象，应立即对溶出仪进行机械验证。若溶出仪不常使用，可适当延长验证周期，一般不超过12个月。	Perform the following in the order given  for mechanical calibration of each apparatus. Some iteration may be necessary  if extensive adjustments are needed. Perform these tests every 6 months or  after any repair, move, etc. If the instrument is not in routine use, the  mechanical calibration may be performed prior to performing the first  dissolution test after the six month interval. Some dissolution instruments  require the use of manufacturer’s supplied special tools or incorporate  automatic mechanical devices to perform the following tests. These may be  used provided they follow the general principle of the procedure.	超过6个月没有使用，在使用前进行再确认应该更合理。
3	（一）溶出仪的水平度    在溶出杯的水平面板上从两个垂直方向上测量，倾斜度均不得超过0.5°。	无
4	（二）篮（桨）轴垂直度    紧贴篮（桨）轴测量垂直度，再沿篮（桨）轴旋转90°测量，每根篮（桨）轴两次测量数值均不得超过0.5°。	Paddle  and Basket Shaft Verticality    Lower the drive unit to where it would be  during an actual dissolution test. If necessary the shaft verticality may be  checked with the shafts raised above the drive unit. Place an accurate bubble  level on the front edge of each of the shafts. The bubble should be within  the lines of the level. Rotate the level 90o so it is on the side of the  shaft. The bubble should again be within the lines of the level for each  shaft. If the shafts are not vertical adjust the feet of the apparatus until  they are vertical. A digital leveling device may also be used to determine  the shaft verticality. The shaft must be ≤0.5° from vertical.	FDA的方法相比CFDA明确了测量位置和具体方法。
5	（三）溶出杯的垂直度    沿溶出杯内壁（避免触及溶出杯底部圆弧部分）测量垂直度，再沿内壁旋转90°测量，每个溶出杯两次测量数值均不得超过1.0°。	Vessel  Verticality    The vessel verticality can be calculated  using the centering measurements and the difference in height between the two  measurements or it can be determined using a digital leveling device placed  on the inside wall of the vessel. The verticality should be determined at two  positions 90° apart. Adjustments can be made by placing shims (such as tape)  under one side of the lip of the vessel or vessel centering collar. The  vessel must be ≤ 1.0° from vertical.    After each vessel has been centered and  made vertical, each vessel and vessel plate opening must be numbered and a  mark must be placed on the lip of each vessel and on the vessel plate  directly next to the mark on the vessel lip. Each vessel must be returned to  the same vessel plate opening and positioned in the exact same position  inside the vessel plate opening for all future dissolution tests.	很重要的一点就是，每个位置的杯、杆、篮和桨都要编号并且固定的。
6	（四）溶出杯与篮（桨）轴的同轴度    篮法：一个测量点位于篮上方距篮上缘2mm，另一个测量点位于篮上方距篮上缘60mm。    桨法：一个测量点位于桨叶上方距桨叶上缘2mm，另一个测量点位于桨叶上方距桨叶上缘80mm。    在上述两个测量点，每个溶出杯轴心与篮（桨）轴轴心的偏差均不得超过1.0mm。    通过了垂直度与同轴度验证的篮轴、桨和溶出杯均应编号，在溶出杯上缘与固定装置相连的位置上做好标记。在进行溶出度试验时，应将各篮轴、桨和溶出杯放在原已通过验证的位置上，保持各溶出杯与固定装置的相对位置不变。为满足同轴度要求，在调整了溶出杯的位置后应重新验证其垂直度。	Vessel  Centering    The vessel plate of an apparatus may warp  or bend or the thickness of a vessel lip or centering collar lip may not be  perfectly uniform. If either of these occurs, even though the shafts are  vertical and the vessel plate is level, the vessel walls may not be vertical.  Use centering tools which measure centering inside the vessel. Two centering  tools are used to center the vessels around the paddle or basket shafts and  to align the vessels so that their sides are vertical. For the paddle method,  the bottom of one centering tool is placed 2 mm above the top of the paddle  blade and the bottom of the second centering tool is clamped on the shaft 80  mm above the blade with the probes positioned in the same direction towards  the glass vessel wall. For the basket method, the bottom of one centering  tool is placed 2 mm above the top of the basket and the bottom of one  centering tool is placed 60 mm above the top of the basket with the probes  positioned in the same direction towards the glass vessel wall. Carefully  lower the shaft and centering tools into the vessels so that the paddle blade  or basket bottom is about 2.5 cm above the bottom of the vessel. Manually  rotate the shaft slowly and check the centering at both levels. If the vessel  is not centered at either level, adjust the vessel to center it. Adjustments  can be made by rotating the vessel or the vessel with the centering collar  inside the vessel plate, moving the vessel sideways within the vessel plate  or placing shims (such as tape) under one side of the lip of the vessel or  vessel centering collar. Repeat this process until both bottom and top  positions are centered within 1.0 mm from the center line. An alternative  procedure is to use a mechanical or digital centering device that centers the  inside of the vessel around the shaft or a surrogate shaft. The centering is  measured at two positions inside the vessel in the cylindrical portion, one  near the top but below the rim and one just above the bottom portion of the  vessel. The shaft or surrogate shaft must be centered within 1.0 mm from the  center line.
7	（五）篮（桨）轴的摆动    在篮（桨叶）上方20mm处测量。篮（桨）轴以每分钟50转旋转时，连续测量15秒钟，每根篮（桨）轴的摆动不得超过1.0mm。	Shaft  Wobble    A runout gauge is placed on top of the  vessel plate, and the drive module is positioned so that the gauge probe  touches the shaft about 2 cm above the top of the paddle blade or basket. The  gauge is placed so that the probe slightly presses in on the turning shaft.  If a mechanical gauge is used, the gauge’s pointer should read slightly more  than zero. The pointer will vary from a minimum to a maximum reading, and the  difference is called the wobble. The specification is ≤1.0 mm total runout.    Basket  Wobble    A runout gauge is placed on top of the  vessel plate and the drive unit is positioned so that the gauge probe touches  the bottom rim of the basket. The gauge is placed so that the probe slightly  presses in on the turning shaft. If a mechanical gauge is used, the gauge’s  pointer should read slightly more than zero. The pointer will vary from a  minimum to a maximum reading and the difference is called the wobble. The  specification is ≤ 1.0 mm total runout.	转速可能影响摆动度，明确转速是很有必要的。
8	（六）篮的摆动    在篮下缘处测量。篮轴以每分钟50转旋转时，连续测量15秒钟，每个篮的摆动不得超过1.0mm。    通过了摆动验证的篮应编号，在进行溶出度试验时，应将各篮放在原已通过验证的位置上，保持与固定装置的相对位置不变。	无	篮足够圆是非常重要的。
9	（七）篮（桨）的深度    测量每个溶出杯内篮（桨）下缘与溶出杯底部的距离，均应为25mm±2mm。	Basket and Paddle Depth The actual  distance between the bottom of the vessel and bottom of the basket or paddle  is determined. If the depth of the basket/paddle is adjustable, first a depth  gauge is used to set the distance between the bottom of the paddle blade or  basket and the bottom of the vessel. The depth gauge is set at 25 mm and  placed on the bottom of the vessel. Each shaft is raised into the apparatus  drive module. The drive unit is then lowered to its operating position. The  paddle or basket is then lowered into the vessel until it touches the top of  the depth gauge. The shafts are locked into this height. This is repeated for  each shaft. The specification is 25 mm ± 2 mm.	如果量块是非金属的，很难保证多年后的高度/直径能够符合要求。
10	（八）篮（桨）轴的转速    将篮（桨）轴的转速设定在每分钟50（100）转。连续记录60秒，各篮（桨）轴的转速均应在50（100）±4%转范围内。	Rotational Speed A tachometer should be  used to measure the rotational speed of the paddle or basket. The shafts  should be rotating smoothly at ± 2 rpm of the target value.	这个FDA更严格一些；应测定每个位置的转速；应注意超出50-100转的方法需要进行相应的确认。
11	（九）溶出杯中的温度    设定好溶出仪的水浴温度，取水900ml注入各溶出杯中，待温度恒定后，测量各溶出杯内溶出介质的温度，均应为37℃±0.5℃。	无	应明确温度计探头放置的位置。
12	（十）振动    溶出仪运转时，整套装置应保持平稳，溶出仪任一部分（包括所处的环境）不应产生明显的移动或振动（≤0.1mil）。	无	应明确转速。
13	无	Sinkers    Sinkers are required for capsules that  float when the Apparatus 2 (Paddle) method is used. Some commercial sinkers  have too many coils that trap the capsule material inside the sinker. DPA uses  sinkers that are recommended by the USP. A detailed procedure on how to make  them is in the proposed USP General Chapter <1092>The Dissolution Procedure:  Development and Validation, USP Pharmacopeial Forum, 31(5), 2005, p. 1463. If  a method states to use a particular commercially available sinker, the DPA  chemist must use the specified sinker.	中国未做规定。
桨板	桨板宽度：74.0± 5.0mm	桨板宽度：74.0mm—75.0mm	CHP标准明显太宽！

北重楼

谢谢！可以了解一下

雪锋

值得学习！

syhorchid

学习一下

毒手药王邓智先

桨板 桨板宽度：74.0± 5.0mm 桨板宽度：74.0mm—75.0mm CHP标准明显太宽！

胜利者

谢谢分享

warfire

很有意义，谢谢楼主

pinna1992

感谢分享！

唐僧洗头爱飘柔

感谢分享！谢谢你

云水泱泱

LZ每次都是干货啊

orochisq

（四）溶出杯与篮（桨）轴的同轴度

  

篮法：一个测量点位于篮上方距篮上缘2mm，另一个测量点位于篮上方距篮上缘60mm。

  

桨法：一个测量点位于桨叶上方距桨叶上缘2mm，另一个测量点位于桨叶上方距桨叶上缘80mm。

  

在上述两个测量点，每个溶出杯轴心与篮（桨）轴轴心的偏差均不得超过1.0mm。

这里有误，应该是

“可通过在溶出杯圆柱体内的篮（桨）轴上下各取一个点，以篮（桨）轴为中心旋转一周，测量篮（桨）轴与溶出杯内壁距离的变化，来表征溶出杯垂直轴与篮（桨）轴的偏离。一个测量点位于溶出杯上部靠近溶出杯上缘，另一个测量点位于溶出杯圆柱体内靠近篮（桨叶）上方。每个溶出杯在2个点测量的最大值与最小值之差均不得超出2.0mm。”

楼主的材料应该是征求意见稿，正式的指导原则发生了变化。

phoebecheng

谢谢楼主的分享

lanran

谢谢！可以学习学习