提供以下两个角度供参考：

1 由于用来评价BCS I 类和 III 类药品，说明在250ml内已溶解完全，故使用500ml或900ml溶出介质进行溶出速率的测定可能影响不大；

2 500ml应该是可以使用的最低限制（介质体积再小则可能影响USP对溶出仪的要求），500ml到900ml中间的范围都可考虑选择；考虑到溶出仪的机械搅拌行为与胃肠内的崩解行为有一定的差别，这一变化可能并不如想象的重要。

Remember this is a biowaiver guidance and so is only applicable to very soluble drugs.  API amount for the largest dosage strength has to be soluble in 250 mL of aqueous media at pHs between pH 1 and pH 6.8 (change here, used to be pH 7.4).  So the drug must already be soluble in 250 mL.  Then comes the dosage form, and here the test is to check that the API dissolves sufficiently rapidly from the dosage form to be completely dissolved in 30 minutes, or for very rapidly dissolving, in 15 minutes.  So we already know the drug is soluble, it is the RATE of dissolution we are measuring. 

Dosage form dissolution testing is an artificial test which probably does not reflect dissolution in the GI tract.  It is subject to artifacts, like the so-called "mounding" effect when the disintegrated tablet or capsule contents gets stuck in a small hill or mound under the paddle and so is not being effectively stirred in the vessel and so dissolves very slowly. I do not know if artifacts are more common in 900 mL of media or 500 mL of media.  The change to the smaller volume will not effect sink conditions (that would occur for these drugs at somewhat less than 250 mL).  You cannot really use less than 500 mL in a dissolution experiment, especially for the basket and only for the paddle if you lower the paddle which means it no longer meets the USP definition of Apparatus II.  I suspect this change makes no real difference and they only did it because they think that the minimum possible volume should be used (ignoring the lack of correlation of this type of testing with the GI tract)

与旧指南相比，2015 指南草案 BCS的判别标准（判断高溶解性， 高渗透性）有如下调整 
A. Solubility – 高溶解性是pH1到pH6.8范围，最高剂量速释剂型的活性成分可完全溶解在250mL水溶液中；而2000年指南规定的是pH1-7.5。
B. Permeability – 高渗透性是有85%以上的量吸收；而2000年指南规定的是90%; 
C. Dissolution – 高溶出是pH1、4.5和6.8，USP第一法装置100转/分钟或USP第二法装置50或75转/分钟的条件下，500mL介质中30分钟取样的溶出限度Q值不少于85%；而2000年指南规定的是900ml;

余煊强2002年的文章 Biopharmaceutics Classification System: The Scientific Basis for Biowaiver Extensions， Pharm Res， 19(7):921-5 提供了以下观点：

1. pH1-7.5是考虑了回肠的pH在6.5-7.4之间，但是一个药物可能需要85分钟才能到达回肠。如果药物是快速溶出的，就可以把溶解条件定在1.0-6.8之间。与溶出度检测的条件是pH1.0， 4.5， 6.8一致。
2. 高渗透性的标准定为90%是保守的，因为对很多已经确认为完全吸收或良好吸收的药物在实验中吸收少于90%。所以建议界限定为85%。
3. 如果在空腹条件下，人的小肠体积变化在50ml到1100ml之间，平均值是500ml。 当喝了一杯水之后，药物会进入在250ml的胃液中，但是如果药物不在胃液溶解，会进入小肠，会有更多的液体。很多药物的吸收，如非甾体抗炎药，是BCS1类药物，是不在胃内溶解，在肠内溶解的，生物利用度90%以上的。研究人员对很多以确定BCS分类的药物和检测条件进行相关性分析。 

本指南草案， C Determining Drug Product Dissolution Characteristics and Dissolution Profile Similarity 章节，仍推荐500ml介质。但是也指出溶出条件是可以调整的。

”If the testing conditions need to be modified to better reflect rapid in vivo dissolution (e.g.， use of a different rotating speed)， such modifications can be justified by comparing in vitro dissolution with in vivo absorption data (e.g.， a relative BA study using a simple aqueous solution as the reference product)“