Copyright © 2006 Elsevier B.V. All rights reserved.
Research paper
Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers
Received 11 March 2006;
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Abstract
Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire® 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol® F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer–Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug–poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.
Keywords: BCS Class II; Rofecoxib; Bioavailability; Dissolution; Polyethylene glycol; Gelucire; Polyols; Hydrotrope; Poloxamer; Release kinetics
Article Outline
- 1. Introduction
- 2. Materials and methods
- 2.1. Materials
- 2.2. Preparation of solid dispersions and corresponding physical mixtures
- 2.3. Phase-solubility studies
- 2.4. In vitro dissolution studies
- 2.5. Powder X-ray diffraction studies
- 2.6. Differential scanning calorimetric studies
- 2.7. Fourier transform infra red spectroscopy
- 2.8. Scanning electron microscopy (SEM)
- 2.9. Data analysis
- 2.9.1. Phase-solubility studies
- 2.9.2. In vitro dissolution data
- 3. Results and discussion
- 3.1. Phase-solubility studies
- 3.2. In vitro dissolution studies
- 3.2.1. Effect of different carriers on the dissolution of RFX from solid dispersions
- 3.2.2. Effect of concentration of the carriers on the dissolution of RFX from solid dispersions
- 3.3. Mathematical modeling
- 3.4. Solid state characterization
- 4. Conclusions
- Acknowledgements
- References







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