In recent years dissolution testing has become increasingly important in the pharmaceutical industry. Dissolution testing provides information on batch homogeneity and conformity, and is routinely used for quality control purposes. In addition, conclusions about the in vivo behavior of the product can be drawn from its in-vitro dissolution behavior. Therefore, the dissolution test has become an indispensable tool in the development of new solid oral dosage forms and the assessment of the physical stability of the formulation. For marketed products dissolution data are of great importance to justify variations and can be under certain conditions a waiver for bioavailability studies. To generate reliable dissolution data a careful development of the dissolution test method is required. An appropriate in-vitro-dissolution test method should meet the following criteria:
- Sufficient discriminatory power Identification of critical manufacturing variables
- Low variability of the method
- Proof of batch homogeneity
- Proof of batch conformity
- In-vitro-in-vivo comparison
- Assessment of the physical stability of the formulation
In order to accomplish these goals standardized dissolution conditions are routinely used at Bayer AG, which are then further optimized based on the test results obtained. The volume of the experimental work highly depends on the stage of the development of the formulation. The influence of the following dissolution parameters on the dissolution profile is generally studied:
- Dissolution medium: pH dependency, type and concentration of surfactant
- Rotation speed of the paddle
- Influence of sinkers
- Deaeration of the medium
When the dissolution conditions are fixed, specification limits for the dissolution have to be defined to ensure the batch-to-batch consistency. A formulation is regarded as an immediate release drug, when at least 80% of the drug substance is dissolved in about 20-30 minutes, corresponding to "Q" = 75%. For modified-release formulations at least three time points have to be chosen for dissolution specifications.