Establishment of in vivo - in vitro Correlation: a Cogent Strategy in Product Development Process

Background: In vivo In vitro correlation (IVIVC) development and its validation is an extremely important phase of dosage form (new as well as generic) optimization. It is a liaison (preferentially linear) between a suitable pharmacokinetic parameter (peak plasma drug conc. i.e. Cmax, time for peak plasma drug conc. i.e. tmax and Area under the Curve i.e. AUC) and in vitro characteristics. Need: During optimization modifications in formulation composition, manufacturing method, required equipments or even in batch size. If these changes are made, in vivo bioavailability study in healthy human volunteers may be required to prove bioavailability of newly developed dosage form with the earlier one. These facts halt the marketing of new formulation with added cost. Thus, it would be enviable to develop in vitro test that corresponds to bioavailability data. Applications: Thus the main purpose of development of IVIVC is to replace in vivo bioavailability and to support bio waivers. As IVIVC comprises linkage between suitable in vivo pharmacokinetic parameter to in vitro characteristic pertaining to dissolution; it can also be used to set up dissolution specifications and/ or validation of methods of dissolution studies. It also assists as means of quality control for certain SUPAC (Scale Up and Post Approval Changes). Moreover there must be some in vitro means to assure batch to batch consistency during large scale manufacturing. After successful establishment of IVIVC; dissolution method used in such establishment is used as routine quality control test as a measure of physiological performance of drug product.