One of the requirements to conduct an appropriate drug dissolution test is to use a sufficient volume of dissolution medium, which should dissolve the expected amount of drug released from a product. This ability of the medium to dissolve the anticipated amount of drug is known as a “sink condition.” It is important to note that a dissolution test should not be conducted in a medium volume that would not dissolve the expected amount of the drug completely and freely. This is because of the obvious reasons that even if a product contains and releases 100% of the drug as expected, one cannot measure (quantify) it because for quantitation/sampling, the drug has to be in the solution. Therefore, it should be noted that this requirement of “freely soluble” or “sink condition” is the requirement for the quantitation (analytical chemistry) and has nothing to do with the physiological aspect. Considering that oftentimes limited volume is available for in vitro dissolution testing, such as with the vessel-based apparatuses, one is required to add some solubilizing agent (e.g., SLS) to create the sink condition for quantitation of the drug.
It is to be noted that a physiological environment deals with the availability of limited volume in a completely different manner. Here, the drug is continuously absorbed into the blood, metabolized, and eliminated, which provides a very efficient mechanism for providing a high solubility equivalent.
On the other hand, the limitation of having a smaller volume in vitro is compensated by the use of a solubilizer. It is very important to note, as has been highlighted in other situations, that to conduct a dissolution test, an analyst needs to simulate, not duplicate, the in vivo environment. This can be explained with an analogy of using a mercury thermometer to monitor body temperature. One does require duplicating the body’s mechanism to monitor the temperature. A human body does not have or require a mercury thermometer to monitor or maintain the body temperature. Furthermore, it also does not care what amount of mercury and what length of thermometer one uses. It is for our own convenience that we use mercury thermometers with the objective that we like to know the temperature of the body at a certain time point.
Similarly, for dissolution testing, we would like to see how a product will behave (release) in a physiological environment represented by an aqueous-based medium with a pH of 5 to 7. If the product is of a highly soluble drug, the analyst needs not do anything further except take the sample and measure the drug to finish the experiment/test. On the other hand, if it is required to test a product having the same formulation as in the previous case but with a low solubility drug, then the analyst may face a problem of quantitation. To address the problem of quantitation, the analyst is required to modify the medium so that it solubilises the drug but should remain physiologically relevant. Therefore, equivalents such as sodium lauryl sulphate are used as the solubiliser for bile salts, which are present in the GI tract. Thus, an analyst must first establish if a solubilizer will be required or not to meet the requirement of dissolving the expected amount of drug in the desired volume of the medium, commonly 900 mL.
Another requirement for the sink condition, often described in the literature, is that of the multiples (2x, 3x, 5x or 10X, etc.) of volumes of medium over and above the volume needed to saturate the medium with the expected amount of drug. It is very important to note that the only requirement for a sink condition is that the volume of the medium should be such that it would provide complete dissolution of the expected amount of the drug. Generally, this condition is fulfilled if an analyst uses a little more (10 to 15%) volume than the volume of the medium (with or without solubilizer) required to dissolve the expected amount of the drug. The multiples as noted above and often described in the literature have no scientific basis and are not supported by any experimental evidence. Therefore, analysts can easily ignore such requirements, if they choose, without any deleterious impact on the dissolution testing or product evaluation.
In short, a sink condition is solely an in vitro requirement which is required to quantify the drug when it is released and dissolved in a dissolution medium. The sink condition may be defined as the volume of dissolution medium, with or without a solubilizer, needed to provide complete dissolution of the expected amount of drug present in the product. One may use any multiple of this volume if so desired. However, scientific and experiment studies do not provide any support to such a requirement or practice.