Modeling the influence of cyclodextrins on oral absorption of low solubility drugs: II. Experimental validation
✍ Scribed by Ece Dilber Gamsiz; Lee Miller; Avinash G. Thombre; Imran Ahmed; Rebecca Lyn Carrier
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 369 KB
- Volume
- 105
- Category
- Article
- ISSN
- 0006-3592
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
A model was developed for predicting the influence of cyclodextrins (CDs) delivered as a physical mixture with drug on oral absorption. CDs are cyclic oligosaccharides which form inclusion complexes with many drugs and are often used as solubilizing agents. The purpose of this work is to compare the simulation predictions with in vitro as well as in vivo experimental results to test the model's ability to capture the influence of CD on key processes in the gastrointestinal (GI) tract environment. Dissolution and absorption kinetics of low solubility drugs (Naproxen and Nifedipine) were tested in the presence and absence of CD in a simulated gastrointestinal environment. Model predictions were also compared with in vivo experimental results (Glibenclamide and Carbamazepine) from the literature to demonstrate the model's ability to predict oral bioavailability. Comparisons of simulation and experimental results indicate that a model incorporating the influence of CD (delivered as a physical mixture) on dissolution kinetics and binding of neutral drug can predict trends in the influence of CD on bioavailability. Overall, a minimal effect of CD dosed as a physical mixture was observed and predicted. Modeling may aid in enabling rational design of CD containing formulations. Biotechnol. Bioeng. 2010; 105: 421–430. © 2009 Wiley Periodicals, Inc.