IVIVC for Fenofibrate Immediate Release Tablets Using Solubility and Permeability as In Vitro Predictors for Pharmacokinetics

The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose®-technique. The in vitro determined drug solubility and permeability data were related to the Cmax values observed from two in vivo human st...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2010-10, Vol.99 (10), p.4427-4436
Main Authors: Buch, Philipp, Holm, Per, Thomassen, Jesper Qvist, Scherer, Dieter, Branscheid, Robert, Kolb, Ute, Langguth, Peter
Format: Article
Language:English
Subjects:
Adult
Aged
bioavailability
Biological and medical sciences
Biological Availability
Chromatography, High Pressure Liquid
Female
Fenofibrate - administration & dosage
Fenofibrate - pharmacokinetics
General pharmacology
Humans
In Vitro Techniques
in vitro/in vivo correlations (IVIVC)
Jejunum - metabolism
Male
Medical sciences
Microscopy, Electron, Transmission
Middle Aged
oral absorption
Permeability
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Solubility
Spectrophotometry, Ultraviolet
surfactants
Tablets
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Summary:The goal of this study was to investigate the in vitro-in vivo correlation (IVIVC) for fenofibrate immediate release (IR) tablet formulations based on MeltDose®-technique. The in vitro determined drug solubility and permeability data were related to the Cmax values observed from two in vivo human studies. Solubility and permeation studies of fenofibrate were conducted in medium simulating the fasted state conditions in the upper jejunum, containing the surfactant compositions of the six formulations at different concentrations. The behavior of all surfactant compositions was characterized by surface tension, dynamic light scattering, and cryo-TEM. The obtained solubility and permeation data were combined and compared with the Cmax values for the fenofibrate formulations, assuming a 50mL in vivo dissolution volume. A good IVIVC was observed for five fenofibrate formulations (R2=0.94). The in vitro studies revealed that the formulation compositions containing sodium lauryl sulfate (SLS) interfered with the vesicular drug solubilizing system of the biorelevant medium and antagonized its solubilization capacity. The opposing interaction of surfactants with the emulsifying physiological constituents in intestinal juice should be taken into consideration in order to prevent unsatisfactory in vivo performance of orally administered formulations with low soluble active pharmaceutical ingredients.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.22148