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Supersaturated dissolution data and their interpretation: the TPGS-carbamazepine model case.
Georgia Charkoftaki1, Aristides Dokoumetzidis, Georgia Valsami
1Laboratory of Biopharmaceutics-Pharmacokinetics, Faculty of Pharmacy, University of Athens, Panepistimiopolis 157 71, Athens, Greece.
The Journal of Pharmacy and Pharmacology
|July 14, 2011
Summary
d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) enhances carbamazepine (CBZ) solubility. A modified dissolution model successfully described supersaturated dissolution curves, particularly at 10°C.
Area of Science:
- Pharmaceutical Sciences
- Physical Chemistry
- Drug Delivery
Background:
- Carbamazepine (CBZ) is a widely used antiepileptic drug with poor aqueous solubility, limiting its bioavailability.
- Understanding drug dissolution is crucial for optimizing oral dosage forms.
- d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is a known solubilizer and absorption enhancer.
Purpose of the Study:
- To investigate the effect of vitamin E TPGS on carbamazepine (CBZ) dissolution from commercial tablets.
- To examine the influence of temperature on CBZ dissolution in the presence of TPGS.
- To modify a reaction-limited dissolution model for describing supersaturated dissolution data.
Main Methods:
- Solubility studies of CBZ were conducted with varying concentrations of TPGS and common excipients (silicon dioxide, microcrystalline cellulose) at 10, 25, and 37°C.
- Dissolution profiles of 200 mg CBZ (Tegretol®) tablets were generated.
- A modified reaction-limited dissolution model was developed and fitted to experimental data.
Main Results:
- CBZ solubility increased in a concentration-dependent manner with TPGS at all tested temperatures.
- Classical supersaturated dissolution curves, with concentration maxima exceeding solubility, were observed at 10°C.
- The developed model accurately described the dissolution data of CBZ in TPGS at 10°C.
Conclusions:
- Vitamin E TPGS significantly enhances carbamazepine solubility across a range of temperatures.
- The modified dissolution model provides a robust framework for analyzing supersaturated drug release profiles.
- This research offers insights into improving CBZ oral bioavailability through formulation strategies.
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