Predicting the effect of fed-state intestinal contents on drug dissolution.
OBJECTIVE
There are several endogenous and exogenous species in the gastrointestinal (GI) tract which can act as solubilizing agents and thereby affect drug dissolution. The purpose of this study is to understand food effects on drug dissolution and provide insight into their anticipated overall effect on absorption and bioavailability.


METHODS
Dissolution kinetics of 15 drugs of variable logP, charge, and molecular weight were tested in simulated intestinal environment. The ability of a film-equilibrium-based model to predict the influence of a simulated intestinal environment on drug dissolution was examined.


RESULTS
The most significant improvement in dissolution kinetics and solubility (up to 6-fold) was evident with highly hydrophobic compounds (logP > 4). Improvement in solubility did not always constitute improvement in dissolution kinetics on a relevant time scale. Comparison of simulation and experimental results indicates that a model considering micelle partitioning as a pseudo-equilibrium process can predict trends in the influence of food-related solubilizing agents on drug dissolution kinetics.


CONCLUSIONS
The significance of food-related solubilizing agents to drug dissolution is not always obvious, as it depends on multiple physicochemical parameters; however, simple modeling may provide insight into food effects on dissolution and, ultimately, overall absorption and bioavailability of compounds considered for oral formulation.
Department of Chemical Engineering, Northeastern University, 342 Snell Engineering Center, Boston, Massachusetts 02115, USA.
Ece Dilber
ED
Gamsiz
Mukul
M
Ashtikar
John
J
Crison
Walt
W
Woltosz
Michael B
MB
Bolger
Rebecca Lyn
RL
Carrier
D002851:Chromatography, High Pressure Liquid; D005502:Food; D005766:Gastrointestinal Contents; D007413:Intestinal Mucosa / Q000378:metabolism*; D008823:Micelles; D008954:Models, Biological; D010316:Particle Size; D010599:Pharmacokinetics; D012995:Solubility
D008823:Micelles