Dissolution tests are employed to establish drug release characteristics of solid oral products, such as tablets and capsules. The rationale for conducting these tests is that for a product to be therapeutically effective, the drug must be released from the product and should generally be dissolved in the fluid of the gastrointestinal (GI) tract. The drug in solution form facilitates the absorption of the drug from the GI tract into the systemic (blood) circulation to reach its desired target (site of action) to exert its effect. Therefore, a dissolution test may be considered as a critical step for the development and assessment of the quality of products linking to their safety and efficacy attributes. Thus, drug dissolution studies are conducted at every stage of a product’s life, including obtaining approval for marketing in a country from local regulatory authorities.
In reality, dissolution testing may be considered as an extraction technique such as a Soxhlet extractor for extracting compounds from their matrixes or perhaps a simple shake-flask technique for solubility determination. It is not to say that dissolution apparatuses may be replaced or substituted by apparatuses for the two types of techniques mentioned, but highlighting the fact that they all work on the same principle but with different objectives. The extraction techniques mentioned concerns with extraction/dissolution to the maximum of the test compounds using rather harsh experimental conditions such as boiling liquids, vigorous shaking and/or stirring at very high speeds. On the other hand, dissolution technique is based on extraction process with rather restrictive choices of solvents, temperature and stirring/shaking. The extraction solvent used in dissolution testing is limited to water or aqueous based solutions having pH in the range pH 5 to 7 and maintained at 37 °C. The stirring and mixing must be thorough but gentle to avoid any harsh abrasive impact on the product. The chosen solvent and experimental conditions are representative of the fluid present in the gastrointestinal (GI) tract to simulate extraction process within the GI tract.
It is important to note that dissolution extractor/tester, which is commonly based on a vessel and stir combination, does not reflect the GI physiology but the environment and process of the extraction within the human GI tract. Following the extraction, as for the other techniques mentioned above, samples are withdrawn, filtered and quantified using any of the common methods such as chromatographic/spectroscopic. The results are commonly obtained in the units of amount/volume (e.g. mg or ?g/mL). However, these results are further converted to other units, for example for solubility expression; they are reported as amount/100 mL. However, results from Soxhlet apparatus or dissolution technique are reported in percentage of the extracted amount based on the total amount of the matrix (Soxhlet) or total expected amount of the drug present in the product.
The preceding discussion about the similarity of the dissolution testing to other extraction techniques is presented to highlight the fact that the drug dissolution testing is a relatively simple analytical technique. It should not require any more elaborate method development/validation steps or reporting of results than for other simple analytical techniques such as the two described above. Such an understanding of the underlying principle of dissolution testing will help in critically evaluating current complex practices of reporting and evaluation the dissolution results and further simplifying them.
