The most commonly reported results from dissolution testing for establishing the performance of oral products (e.g. tablets/capsules), in particular for immediate-release (IR) products, is that products should meet a criterion of not less than 80% drug dissolution within less than 60 minutes, mostly 30 minutes.

Let us assume that a dissolution test (n=6) provides the following results (% drug dissolved) at 30 minutes (96, 88, 65, 110, 66, 65; Ave = 82; RSD = 23%). Obviously, this test/product, with at Q of 80%, would not meet the USP tolerance at the first stage. However, with a bit of luck and a second round of testing of 6 units it may meet/pass the USP Tolerance criteria. For details, please see the link, in particular the data set in row one.

Let us discuss the interpretation of these observed results. Continue reading →

Drug absorption from the GI tract is generally dependent on dissolution characteristics of a product which in turn is dependent on the aqueous solubility of the drug. In general, it is assumed that the higher the solubility, the higher the expected drug absorption will be, and vice versa.

Before considering the link between absorption and solubility, it should be prudent to define and establish the solubility characteristics of a drug for absorption purposes. In this regard, it is a well-known fact that drugs are mostly absorbed from the intestinal part of the GI tract (link). The liquid phase in the intestine is aqueous-based having a pH in the range of 5 to 7. For all practical purposes one may consider a pH of 6 (average of 5 to 7) for the intestinal fluid. Thus, to represent intestinal fluid, for dissolution testing, one may use water itself, which usually has pH around 6 or a (phosphate) buffer having a pH of 6. Therefore, in the following discussion, solubility of drugs in water will only be considered.

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The quality of a solid oral dosage form, such as a tablet or capsule product, may be defined as its ability to provide expected and consistent (reproducible) drug levels in plasma/blood. The product is introduced into the GI tract through the oral cavity (mouth) to release its drug, which gets dissolved in the aqueous milieu and gets transferred into the blood stream to produce its therapeutic effects.

This transfer of a drug from the GI tract to the blood stream is described by different terminologies, often interchangeably, such as permeability, absorption and bioavailability of the drug.  However, these terminologies have distinct meanings, and for clarity purposes should not be interchangeably used. The purpose of this article is to describe and explain these terminologies to facilitate an appropriate development and evaluation of the products in particular for the use of in vitro drug dissolution testing.  Please click here for complete article

At the product development stage the objective is to develop a product (tablet/capsule) having certain desired drug release/dissolution characteristics in humans. Therefore, one requires a dissolution method mimicking in vivo or the GI tract environment (in particular that of the intestinal). Commonly, this in vivo environment for dissolution testing purposes is represented by three variants: (i) temperature (37 ºC); (ii) an aqueous based solvent/medium; (iii) a container or vessel with a stirrer to provide interaction between product and solvent.

Another requirement, which is perhaps the most critical one and is often overlooked, is that the method or testing environment must also be product independent as does the GI tract environment.

It is further important to note that the method to be used must have already been developed and validated independently of the product which is underdevelopment. On the other hand, it is a common practice that people use or develop product dependent dissolution methods. However, unfortunately such a practice is neither scientifically valid nor correct. Furthermore, the use of a product dependent method cannot provide true or actual dissolution characteristics of the product (link).

At present, none of the commonly suggested/recommended testers/methods, including pharmacopeial, provide common and/or product independent methods or experimental conditions. Thus such tests/methods cannot provide scientifically valid and/or true dissolution characteristics of a product during the product development stage.

This present day limitation can easily be addressed with the use of the crescent-shape spindle set at 25 rpm with 900 mL of water maintained at 37 ºC. A small amount solubilizer may be added to water/medium if the drug is of low aqueous solubility. For more details regarding advantages of using crescent-shape spindle please follow the link.