In Vitro-In Vivo Correlation (IVIVC) and Determining Drug Concentrations in Blood from Dissolution Testing A Simple and Practical Approach~!2009-10-30~!2010-01-04~!2010-04-29~!

Evaluating an IVIVC is a desirable feature for any drug dissolution test to establish relevance and confidence in assessing the quality and safety of solid oral dosage products, such as tablets and capsules. However, success in this area has been limited. One of the reasons for this lack of success may be that the approaches described in the literature to achieve IVIVC appear to be intuitive expectations rather than an objective end-point based on scientific rationale. For ex- ample, rather than predicting an in vivo response based on in vitro results, which is the objective of IVIVC, attempts are usually made to match in vitro results with in vivo results by adjusting experimental conditions for in vitro testing. This ar- ticle provides a discussion and clarification on the underlying scientific principles to help in alleviating current difficulties in developing IVIVC. Further, it provides a simpler and practical approach based on experimental studies to achieve ap- propriate IVIVC by predicting blood drug levels from dissolution results. For a drug to be absorbed into the blood stream to reach its site of action it should be present in a solution form in the GI tract, more specifically in the intestine. The in vitro disso- lution testing is conducted to estimate or predict dissolution of the drug in the GI tract or in vivo. Therefore, some form of relationship between these two dissolution types is desir- able and it is commonly referred in the literature as in vitro- in vivo co-relationship (IVIVC). Developing and conducting a dissolution test based on such a relationship not only en- hances the credibility of an in vitro test but also provides a number of ethical and economical benefits such as reduction of the required number of in vivo studies in humans, thus simplifying and expediting the development and modifica- tion of the drug products.