Can dosage form-dependent food effects be predicted using biorelevant dissolution tests? Case example extended release nifedipine.
OBJECTIVE
Food intake is known to have various effects on gastrointestinal luminal conditions in terms of transit times, hydrodynamic forces and/or luminal fluid composition and can therefore affect the dissolution behavior of solid oral dosage forms. The aim of this study was to investigate and detect the dosage form-dependent food effect that has been observed for two extended-release formulations of nifedipine using in vitro dissolution tests.


METHODS
Two monolithic extended release formulations, the osmotic pump Adalat® XL 60mg and matrix-type Adalat® Eins 30mg formulation, were investigated with biorelevant dissolution methods using the USP apparatus III and IV under both simulated prandial states, and their corresponding quality control dissolution method. In vitro data were compared to published and unpublished in vivo data using deconvolution-based in vitro - in vivo correlation (IVIVC) approaches.


RESULTS
Quality control dissolution methods tended to overestimate the dissolution rate due to the excessive solubilizing capabilities of the sodium dodecyl sulfate (SDS)-containing dissolution media. Using Level II biorelevant media the dosage form dependent food effect for nifedipine was described well when studied with the USP apparatus III, whereas the USP apparatus IV failed to detect the positive food effect for the matrix-type dosage form.


CONCLUSIONS
It was demonstrated that biorelevant methods can serve as a useful tool during formulation development as they were able to qualitatively reflect the in vivo data.
Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Max-von-Laue Strasse 9, 60438 Frankfurt am Main, Germany.
Cord J
CJ
Andreas
Pfizer Ltd., Discovery Park House, Sandwich, Kent CT13 9NJ, England, United Kingdom.
Irena
I
Tomaszewska
Bayer Pharma AG, Research Center Wuppertal-Aprath, Wuppertal, Germany.
Uwe
U
Muenster
Bayer Pharma AG, Research Center Wuppertal-Aprath, Wuppertal, Germany.
Dorina
D
van der Mey
Bayer Pharma AG, Research Center Wuppertal-Aprath, Wuppertal, Germany.
Wolfgang
W
Mueck
Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Max-von-Laue Strasse 9, 60438 Frankfurt am Main, Germany. Electronic address: Dressman@em.uni-frankfurt.de.
Jennifer B
JB
Dressman
D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D018565:Food-Drug Interactions; D006801:Humans; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology*; D012995:Solubility
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D009543:Nifedipine
Biorelevant dissolution testing; Clinical study; Extended release; Food effects; IVIVC; Nifedipine; USP apparatus III (BioDis); USP apparatus IV (flow through cell)