In Vitro–In Vivo Correlation (IVIVC): A Strategic Tool in Drug Product Development

Abstract

Abstract:

In a recent era many concepts are dealing as an emerging tool for the drug delivery application like Biopharmaceutical Classification System (BCS), In-vitro and In-vivo study, and Bioavailability/Bioequivalence (BA/BE) study etc.  To determine Therapeutic efficiency in-vitro is not enough so the concept of In-vitro-In-vivo correlation (IVIVC) is playing as an convincing correlation with this for concept of pharmaceutical dosage forms have been a main focus of attention of pharmaceutical industry, academia, and regulatory sectors. Formulation, Development and optimization of dosage form is an integral part of Research governed by technology transfer to scale up the manufacturing and then concurrent validation governed from the marketing of any therapeutic agent which is indeed a time consuming and costly process. A good correlation is a tool for predicting in-vivo results based on in-vitro data using IVIVC which gives indirect cost effective approach to dosage form optimization of trials in human, fixes dissolution acceptance criteria, and can be used as a tool to substitute for further bioequivalence studies; it is also recommended by regulatory authorities. Most correlations between in-vitro and in-vivo data (IVIVC) rely on linear relationships but sometimes it may not give linear behaviour due to some more factors in the actual in-vivo study. However, nonlinear IVIVC can be also observed, justified and validated. Thus the need for a tool to reliably correlate in-vitro and in-vivo drug release data has exceedingly increased. Such a tool shortens the drug development period, economizes the resources and leads to improved product quality. Increased activity in developing IVIVCs indicates the value of IVIVCs to the pharmaceutical industry. IVIVC can be used in the development of new pharmaceuticals to reduce the number of human studies during the formulation development as the main objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and to support biowaivers. It supports and/or validates the use of dissolution methods and specification adjustment. This review article represents the FDA guidance, development, evaluation, and validation of an IVIVC to grant biowaivers, and to set dissolution specifications for oral dosage forms, biopharmaceutical classification systems (BCS), BCS biowaivers, and applications of BCS in IVIVC development and concept of mapping. The importance of dissolution media and methodology and pharmacokinetic studies in the context of IVIVC has been highlighted. The principles of IVIVC also merged with non-oral products such as parenteral depot formulations and novel drug delivery systems as well.

Key Words: Fundamentals of IVIVC, Biopharmaceutical Classification System (BCS), Objectives, Biowaiver, Levels, Correlation, Dissolution methodologies, IVIVC of Novel Dosage Forms, Applications of IVIVC.