In Vitro-In Vivo Correlations

This book represents the invited presentations and some of the posters presented at the conference entitled "In Vitro-In Vivo Relationship (IVIVR) Workshop" held in Sep­ tember, 1996. The workshop was organized by the IVIVR Cooperative Working Group which has drawn together scientists from a number of organizations and institutions, both academic and industrial. In addition to Elan Corporation, which is a drug delivery com­ pany specializing in the development of ER (Extended Release) dosage forms, the IVIVR Cooperative Working Group consists of collaborators from the University of Maryland at Baltimore, University College Dublin, Trinity College Dublin, and the University of Not­ tingham in the UK. The principal collaborators are: Dr. Jackie Butler, Elan Corporation Prof. Owen Corrigan, Trinity College Dublin Dr. lain Cumming, Elan Corporation Dr. John Devane, Elan Corporation Dr. Adrian Dunne, University College Dublin Dr. Stuart Madden, Elan Corporation Dr. Colin Melia, University of Nottingham Mr. Tom O'Hara, Elan Corporation Dr. Deborah Piscitelli, University of Maryland at Baltimore Dr. Araz Raoof, Elan Corporation Mr. Paul Stark, Elan Corporation Dr. David Young, University of Maryland at Baltimore The purpose of the workshop was to discuss new concepts and methods in the devel­ opment of in vitro-in vivo relationships for ER products. The original idea went back ap­ proximately 15 months prior to the workshop itself. For some time, the principal collaborators had been working together on various aspects of dosage form development.

1. Examples of in Vitro-in Vivo Relationships with a Diverse Range of Quality.- 2. Dissolution Assay Development for in Vitro-in Vivo Correlations: Theory and.- 3. In Vitro Dissolution Profile Comparison and IVIVR: Carbamazepine Case.- 4. A General Framework for Non-Parametric Subject-Specific and Population Deconvolution Methods for in Vivo-in Vitro Correlation.- 5. Convolution-Based Approaches for in Vivo-in Vitro Correlation Modeling.- 6. Approaches to IVIVR Modelling and Statistical Analysis.- 7. Validation of in Vitro-in Vivo Correlation Models.- 8. Examples of Developing in Vitro-in Vivo Relationships.- 9. The Biopharmaceutic Drug Classification and Drugs Administered in Extended Release (ER) Formulations.- 10. Investigating in Vitro Drug Release Mechanisms Inside Dosage Forms: Monitoring Liquid Ingress in HPMC Hydrophilic Matrices Using Confocal Microscopy.- 11. Determination of Critical Manufacturing and Formulation Variables for a Hydrophilic Matrix Tablet Formulation Using an in Vitro Discriminatory Dissolution Method.- 12. Artificial Neural Network Based in Vitro-in Vivo Correlations.- 13. Setting Dissolution Specifications for Modified-Release Dosage Forms.- 14. Review of Methodologies for the Comparison of Dissolution Profile Data.- 15. Assessing Whether Controlled Release Products with Differing in Vitro Dissolution Rates Have the Same in Vivo-in Vitro Relationship.- 16. Comparison of Methodologies for Evaluating Regional Intestinal Permeability.- 17. In Vitro-in Vivo Relationships of Several “Immediate” Release Tablets Containing a Low Permeability Drug.- 18. Nonlinear in Vitro-in Vivo Correlations.- 19. Use of Nonlinear Mixed Effects Modelling in the Development of in Vitro-inVivo Correlations.- 20. The Development of a Novel in Vitro DiscriminatoryDissolution Method for a Class I Drug in a Matrix Tablet Formulation.- 21. In Vivo-in Vitro Evaluation of the Impact of Accelerated Stability Conditions on a Hydrophilic Matrix Tablet.- 22. Development of in Vitro-in Vivo Correlations Using Various Artificial Neural Network Configurations.- 23. Impact of IVIVR on Product Development.- 24. The Role of in Vitro-in Vivo Correlations (IVIVC) to Regulatory Agencies.- 25. Draft Guidance for Industry Extended-Release Solid Oral Dosage Forms: Development, Evaluation and Application of in Vitro-in Vivo Correlations.- 26. Issues Important to in Vitro-in Vivo Correlation: IVIVR Workshop Open Discussion.