Development of In Vitro–In Vivo Correlation for Extended‐Release Niacin After Administration of Hypromellose‐Based Matrix Formulations to Healthy Volunteers. Issue 11 (24th September 2014)

• Record Type: Journal Article
• Authors: Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter‐Jan; Vargo, Ryan
• Is Part Of: Journal of pharmaceutical sciences. Volume 103:Issue 11(2014:Nov.)
• Page Start: 3713
• Page End: 3723
• Publication Date: 2014-09-24
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24179
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Development of <italic>in vitro</italic>–<italic>in vivo</italic> correlations (IVIVCs) for extended‐release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross‐over study against immediate‐release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3713–3723, 2014</p> </abstract>