Recently a question was asked as to whether my suggested approach of IVIVP for predicting plasma drug levels, based on convolution technique, is applicable for evaluating the stability samples as well. The answer is yes, an explanation follows:
It appears that this question originates from the current thinking and belief that dissolution methods depend on the nature and source of a product. For example: it is quite common that different products such as IR and ER are often analyzed using different dissolution methods. Similarly, often dissolution methods for QC purposes and for product development are different. Unfortunately, this current thinking i.e. product dependent dissolution testing, is not correct.
Appropriate prediction of plasma drug levels requires that dissolution results should be obtained using physiologically relevant experimental conditions. As the physiological (GI tract) condition or environment is independent of the nature or source of the product one, therefore, requires the use of product independent dissolution testing as well.
The artefact of the poor stirring and mixing within dissolution vessels dictates that the tests using paddle and basket apparatuses should be conducted using product dependent experiment conditions. Therefore, results obtained using these apparatuses cannot be considered as physiologically relevant. The predicting of plasma drug levels to evaluate products using these apparatuses obviously becomes a futile exercise.
To overcome this deficiency, a new stirrer has also been proposed which is known as a crescent shape spindle. This spindle provides an efficient and reproducible stirring environment, thus have the ability of providing a single and product independent dissolution testing environment. The suggested dissolution testing experimental conditions are: 900 mL of distilled water maintained at 37 °C using the crescent shape spindle set at 25 rpm. A small of amount of solubiliser (e.g. SLS) may be required for drugs which have low solubility in water.
As the experimental conditions are set, the tester becomes a tester in the true sense of the word, meaning that the analyst can just drop the product (tablet/capsule) into the vessel and measure the dissolution. The source of product (stability, QC, product development or from a stability study) is immaterial. In fact, a dissolution tester must possess such a quality and have the ability to be used to determine dissolution characteristics of a product, because the analyst likes to evaluate the impact of variation in products based on dissolution results. If a dissolution test is dependent on the product or its source then one cannot observe or compare the effect of variations of the products on dissolution, which would defeat the purpose of the dissolution testing.
For dissolution testing purposes, the tester with a crescent shape spindle should be considered exactly like a spectrophotometer. In the case of a spectrophotometer, which measures the absorption value of a solution, the solution can be from any of the sources such as tablets/capsules (QC, stability, product development). Analysts measure the absorbance and calculate the concentration of the solution and relate it to the product. Similarly, a dissolution tester with the crescent shape spindle provides the rate of solution formation or dissolution and the product (table/capsules) can be from any source QC, stability or product development. The dissolution tester is and should be blinded to the source. An analyst takes out dissolution samples, measures the concentration of the solutions, and report the results as percent drug released with time or further convert these results into plasma drug levels using the suggested convolution (mathematical manipulation/calculation) approach. The results are then related back to the product to establish consistency and change in its quality. It is to be noted that both the tester, including the experimental condition, and the calculation of plasma levels are independent of type and source of products. It is, indeed, a truly simple yet an extremely powerful approach for measuring dissolution and then predicting plasma drug levels leading to products development and evaluation.
A more detailed description and discussion on the crescent shape spindle, suggestion and use of a single set of experimental conditions and convolution approach may found in scientific literature and/or on the website (www.drug-dissolution-testing.com). If you have a question or would like further information in this regard, you may obtain it by writing to moderator@drug-dissolution-testing.com
