Modeling the influence of cyclodextrins on oral absorption of low-solubility drugs: I. Model development
Article first published online: 1 SEP 2009
Copyright © 2009 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 105, Issue 2, pages 409–420, 1 February 2010
How to Cite
Gamsiz, E. D., Miller, L., Thombre, A. G., Ahmed, I. and Carrier, R. L. (2010), Modeling the influence of cyclodextrins on oral absorption of low-solubility drugs: I. Model development. Biotechnol. Bioeng., 105: 409–420. doi: 10.1002/bit.22523
- Issue published online: 21 DEC 2009
- Article first published online: 1 SEP 2009
- Accepted manuscript online: 1 SEP 2009 12:00AM EST
- Manuscript Accepted: 25 AUG 2009
- Manuscript Revised: 13 AUG 2009
- Manuscript Received: 5 JUN 2009
- poorly-soluble drugs;
The ability to quantitatively predict the influence of a solubilization technology on oral absorption would be highly beneficial in rational selection of drug delivery technology and formulation design. Cyclodextrins (CDs) are cyclic oligosaccharides which form inclusion complexes with a large variety of compounds including drugs. There are many studies in the literature showing that complexation between CD and drug enhances oral bioavailability and some demonstrating failure of CD in bioavailability enhancement, but relatively little guidance regarding when CD can be used to enhance bioavailability. A model was developed based upon mass transport expressions for drug dissolution and absorption and a pseudo-equilibrium assumption for the complexation reaction with CD. The model considers neutral compound delivered as a physical mixture with CD in both immediate release (IR) and controlled release (CR) formulations. Simulation results demonstrated that cyclodextrins can enhance, have no effect, or hurt drug absorption when delivered as a physical mixture with drug. The predicted influence depends on interacting parameter values, including solubility, drug absorption constant, binding constant, CD:drug molar ratio, dose, and assumed volume of the intestinal lumen. In general, the predicted positive influence of dosing as a physical mixture with CD was minimal, alluding to the significance of dosing as a preformed complex. The model developed enabled examination of which physical and chemical properties result in oral absorption enhancement for neutral drug administered as a physical mixture with CD, demonstrating the utility of modeling the influence of a drug delivery agent (e.g., CD) on absorption for rational dosage form design. Biotechnol. Bioeng. 2010; 105: 409–420. © 2009 Wiley Periodicals, Inc.