J Pharm Pharmaceut Sci (www. cspsCanada.org) 9 (2): 169-189, 2006 169 In vitro - In vivo Correlation: From Theory to Applications Jaber Emami Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran, Received March 20, 2006; Revised April 28, 2006; Accepted June 13, 2006; published June 16, 2006. ____________________________________ ABSTRACT. A key goal in pharmaceutical development of dosage forms is a good understanding of the in vitro and in vivo performance of the dosage forms. One of the challenges of biopharmaceutics research is correlating in vitro drug release information of various drug formulations to the in vivo drug profiles (IVIVC). 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 settings. This is because the IVIVC includes in vivo relevance to in vitro dissolution specifications. It can also assist in quality control for certain scale-up and post-approval changes (SUPAC). With the proliferation of modified-release products, it becomes necessary to examine the concept of IVIVC in greater depth. Investigations of IVIVC are increasingly becoming an integral part of extended release drug development. There must be some in vitro means of assuring that each batch of the same product will perform identically in vivo. 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, biopharmaceutics classification systems (BCS), BCS biowaivers, application 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 review also covers the literature examples of IVIVCs regarding internal and external validation, compendial dissolution assessment, formulation dependency of IVIVCs, and IVIVCs of pure enantiomers versus racemate drugs. The same principles of IVIVC used for oral extended release products may be applied for non-oral products such as parenteral depot formulations and novel drug delivery systems as well. INTRODUCTION In recent years, the concept and application of the in vitro-in vivo correlation (IVIVC) for pharmaceutical dosage forms have been a main focus of attention of pharmaceutical industry, academia, and regulatory sectors. Development and optimization of formulation is an integral part of manufacturing and marketing of any therapeutic agent which is indeed a time consuming and costly process. Optimization process may require alteration in formulation composition, manufacturing process, equipment and batch sizes. If these types of changes are applied to a formulation, studies in human healthy volunteers may be required to prove that the new formulation is bioequivalent with the old one. Certainly, implementation of these requirements not only halts the marketing of the new formulation but also increases the cost of the optimization processes. It would be, desirable, therefore, to develop in vitro tests that reflect bioavailability data. A regulatory guidance for both immediate- and modified-release dosage forms has been, therefore, developed by the FDA to minimize the need for bioavailability studies as part of the formulation design and optimization. IVIVC procedures are specific to certain countries but could be adopted or used as the background for regulatory recommendations by other countries. IVIVC can be used in the development of new pharmaceuticals to reduce the number of human studies during the formulation development. The main objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and to support biowaivers. IVIVCs could also be employed to establish dissolution specifications and to support and/or validate the use of dissolution methods. ________________________________________ Correspondence: Dr. Jaber Emami Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran, Tel: 98 (311) 792-2586, Fax: 98 (311) 668-0011, E-mail: emami@pharm.mui.ac.ir