In vitro dissolution profile comparison and IVIVR. Carbamazepine case.
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.
Sathe
P
P
Office of Pharmaceutical Sciences, U.S. Food and Drug Administration, Rockville, Maryland 20855, USA.
Tsong
Y
Y
Shah
V P
VP
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
D004304:Dosage Forms; D013607:Tablets; D002220:Carbamazepine