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Enhancing the bioavailability of ABT-963 using solid dispersion containing Pluronic F-68
Y Chen1, G G Z Zhang, J Neilly
1Abbott Laboratories, Global Pharmaceutical R&D, 1401 Sheridan Road, North Chicago, IL 60064, USA. yisheng.1.chen@abbott.com
International Journal of Pharmaceutics
|October 27, 2004
Summary
Solid dispersions with Pluronic F-68 significantly enhance the dissolution and bioavailability of poorly water-soluble ABT-963. This formulation approach shows promise for improving drug delivery and therapeutic efficacy.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Materials Science
Background:
- ABT-963 is a poorly water-soluble compound requiring formulation strategies for improved bioavailability.
- Pluronic F-68 is a polymer carrier investigated for its potential in drug delivery.
Purpose of the Study:
- To develop and characterize solid dispersions of ABT-963 using Pluronic F-68.
- To evaluate the impact of solid dispersion on the in vitro dissolution and in vivo oral bioavailability of ABT-963.
Main Methods:
- Solid dispersions prepared by solvent evaporation and hot-melt extrusion.
- Characterization using DSC, PXRD, SEM, and elemental mapping.
- In vitro dissolution studies and in vivo oral bioavailability studies in fasted dogs.
Main Results:
- A eutectic mixture of ABT-963 and Pluronic F-68 was formed at approximately 7.5% composition.
- Solid dispersions exhibited crystalline drug and polymer across a wide composition range.
- Substantial increase in in vitro dissolution rate of ABT-963 was observed.
- Significant increase in oral bioavailability in fasted dogs compared to conventional capsules.
Conclusions:
- Solid dispersion formulation with Pluronic F-68 effectively improves ABT-963 dissolution and bioavailability.
- This approach is a promising strategy for developing drug products of poorly water-soluble compounds like ABT-963.