One of the requirements to conduct an appropriate drug dissolution test is to use a sufficient volume of dissolution medium, which should be able to dissolve the expected amount of drug released from a product. This ability of the medium to dissolve the expected amount of drug is known as a “sink condition”. It is important to note that a dissolution test should not be conducted in a volume of the medium which 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 often times limited volume is available for in vitro dissolution testing such as with the vessel based apparatuses, one is required to add some solubilising 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 blood, metabolised 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 solubiliser. It is very important to note, as has been highlighted in other situations as well, 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 the body temperature. One does not 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 what the temperature of the body is at a certain time point.
Similarly, for dissolution testing we would like to see how a product will behave (release) in a physiological environment which is represented by an aqueous based medium having a pH of 5 to 7. If the product would be of a highly soluble drug, the analyst needs not to do any thing further except taking the sample and measuring the drug to finish off 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 in such a way that it solubilises the drug but should remain physiologically relevant as well. Therefore, for bile salts, which are present in the GI tract, equivalents such as sodium lauryl sulphate are used as the solubiliser. Thus, an analyst must first establish if a solubiliser 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 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 solubiliser) required to dissolve the expected amount of the drug. The multiples as noted above and often described in 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 solubiliser, 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.
