title: In vitro dissolution profile comparison and IVIVR. Carbamazepine case.
abstract: Dissolution data for the immediate or modified release drug products are usually collected as percent dissolved at multiple time points. Once an in-vitro/in-vivo relationship is established on a drug product, the dissolution profile becomes meaningful and important. In that context, if a firm desires to modify its formulation on which the in-vitro/in-vivo association has been established, a meaningful insight into the pharmacokinetics may be obtained by comparing the dissolution profiles of the two lots. In this presentation, we demonstrated a model dependent dissolution profile comparison approach using example of carbamazepine tablet dissolution data. Once a mathematical function was selected to describe the dissolution data coming from various standard lots, a similarity region could be constructed using the model parameter variances. To compare the test and reference lot dissolution profiles, a statistical distance was calculated between the mean parameters. A confidence region generated around the normalized mean statistical distance could then be compared with the similarity region to assess the similarity or dissimilarity of the dissolution profiles.
authors.affiliation: Office of Pharmaceutical Sciences, U.S. Food and Drug Administration, Rockville, Maryland 20855, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sathe
authors.forename: Y
authors.initials: Y
authors.lastname: Tsong
authors.forename: V P
authors.initials: VP
authors.lastname: Shah
mesh_terms: D001682:Biological Availability; D001699:Biometry; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004304:Dosage Forms; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D013607:Tablets
chemical_list: D004304:Dosage Forms; D013607:Tablets; D002220:Carbamazepine