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European Journal of Pharmaceutics and Biopharmaceutics
Volume 65, Issue 1, January 2007, Pages 26-38
 
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doi:10.1016/j.ejpb.2006.07.007    How to Cite or Link Using DOI (Opens New Window)
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

Naveen Ahujaa, Om Prakash Katarea and Bhupinder SinghCorresponding Author Contact Information, a, E-mail The Corresponding Author

aUniversity Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India

Received 11 March 2006; 
revised 14 June 2006; 
accepted 13 July 2006. 
Available online 20 July 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
2.9.2.1. Mathematical modeling of release kinetics
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
3.4.1. Powder X-ray diffraction spectroscopy
3.4.2. Fourier transform infrared spectroscopy
3.4.3. Differential scanning calorimetry studies
3.4.4. Scanning electron microscopy
4. Conclusions
Acknowledgements
References






 
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