Use of in vitro-in vivo correlation to predict the pharmacokinetics of several products containing a BCS class 1 drug in extended release matrices.
OBJECTIVE
To determine if an IVIVC model can predict PK profiles of varying formulations of a BCS Class 1 drug that is a salt of a weak base.


METHODS
An IVIVC model (Level A) was created by correlating deconvoluted in vivo absorption data obtained from oral administration of 50 mg, 100 mg, and 200 mg fast and slow extended release formulations with in vitro percent dissolved using residual regression analysis. The model was then used to predict the in vivo profile of five test products that varied in formulation characteristics.


RESULTS
The model passed internal validation for predicted Cmax and AUC. For external validation, in vitro data of five different test formulations was utilized. The model passed external validation for two test formulations that were different but belonging to the same release mechanism as that of the reference formulation. Three formulations failed external validation because they belonged to either a mixed or different release mechanism. The model and results were further confirmed using GatstroPlus™ simulation software.


CONCLUSIONS
These observations indicate that an IVIVC model for a BCS class I drug may be applicable to varying formulations if the principle of the drug release is similar.
Food and Drug Administration Division of Product Quality Research, CDER/OPS/OTR/DPQR, White Oak, LS Building 64 10903 New Hampshire Ave, Silver Spring, Maryland 20993, USA. Tahseen.mirza@fda.hhs.gov
Tahseen
T
Mirza
Srikant A
SA
Bykadi
Christopher D
CD
Ellison
Yongsheng
Y
Yang
Barbara M
BM
Davit
Mansoor A
MA
Khan
D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D003198:Computer Simulation; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D010599:Pharmacokinetics; D012044:Regression Analysis; D012995:Solubility
D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations