Developing a dissolution method requires an apparatus with associated experimental conditions capable of providing an expected outcome, in this case dissolution characteristics of a reference product. The dissolution characteristics of the reference product must be known and established independently. As, at present, there is no reference product available with known or accepted drug release characteristics, one cannot develop a dissolution method, in the true sense of the concept and/or practice of analytical chemistry.

However, this limitation may be addressed by using the concept of relative dissolution. i.e. developing a method (apparatus and associated experimental conditions) which will be capable of differentiating dissolution characteristics of approved IR and ER products of the same drug. Also, this differentiation in dissolution results should be achieved within the dosing interval of these (IR and ER) products. The practice of such an exercise will be called “dissolution method development” and such a method should be used for determining the dissolution characteristics of a test product. As a rule, an appropriate dissolution method has to be product independent.

It is important to note that a dissolution method cannot be developed using a product which is being developed. One should be careful in reading and interpreting the literature in this regard.

It is often described in literature that method developments for poorly/sparingly soluble drugs pose special challenges, thus, may require a more careful and elaborate approach. Such views do not appear to be convincing.

First of all a dissolution test is conducted for a product (tablet/capsule) not for a drug. Therefore, if the product (formulation/manufacturing) remains the same, containing either a freely or sparingly soluble drug, then the same method should perform well. However, the difference will be in the monitoring (quantitation). If an appropriate medium is not used, then quantitation would either be erratic or not possible for low solubility drugs.

On the other hand, often quantitation does not cause problems, because as a fundamental requirement, a dissolution test should only be conducted under a sink condition i.e. the expected amount of drug from the product must be freely soluble in the medium. This “sink” condition is established prior to method development. Therefore, it is important to note that high or low solubility relates to general aqueous solubilities of drugs, not to dissolution medium or testing. For a dissolution test a drug must be freely soluble, therefore, both (high and low solubility drugs) are equivalent for dissolution testing.

The question is then why do the products of these two types of drugs often behave differently in dissolution testing so that they required a different classification or different approaches. The reason is that it is because of the poor interaction between the product (disintegrated) content and the dissolution medium. Due to poor hydrodynamics within dissolution vessels, paddle and basket, the product contents tends to accumulate at the bottom. This accumulation is known as “cone” formation (as shown in the picture). Often such pronounced “cones” are not observed with the basket apparatus, but similar accumulation/settling of the product contents at the bottom of the vessel is present. Depending on the size of the “cone”, the release of the drug from the “cone” will be different, mostly slower and erratic than expected. The size and shape of the “cone” will depend on the excipients (nature and amount). Bulkier and larger amounts of excipients would have a greater impact. In short, it is not a problem because of the low aqueous solubility of a drug or the product itself, but poor hydrodynamic (stirring and mixing) in a dissolution vessel whether it is paddle or basket apparatus. Unfortunately, this is an inherent weakness of the paddle and basket stirrers and cannot be resolved.

In conclusion, classification of high (freely) or low (sparingly) solubility drugs do not appear relevant for drug dissolution test purposes.

A commonly asked question is how should one choose between Paddle and Basket apparatuses when selecting an apparatus? In short there is no clear cut answer, in particular based on a scientific merit or reasoning.

It is important to note that both of these apparatuses have been shown to provide highly variable and unpredictable results. Furthermore, the results obtained using these apparatuses often lack a link to physiological or in vivo characteristics of the test products. These apparatuses usually provide two different sets of results for the same product under similar operating conditions. Thus, it would be impossible to know which one is reflecting the actual/true dissolution behaviour of the product. Between the two, the Basket apparatus appears to provide more variable results than the Paddle apparatus.

It appears that traditional practices/views, rather than scientific merit, are used in selecting the apparatuses. For example, it is commonly suggested that the Basket apparatus may be preferred for products which may float in the dissolution vessels. On the other, hand, such floatation may be controlled with the use of a “sinker” if one prefers to use a Paddle apparatus. Eventually, it boils down to the personal preference of an analyst, as to what his or her expectations are for the dissolution behaviour of the test product.

In short, current practices are to choose an apparatus which would provide desired dissolution results (behaviour) of the test product. How useful or relevant would such results be? This remains an open and debatable question.