Drug-cyclodextrin complexes: an approach to enhance the solubility and dissolution properties of poorly soluble drugs
Rudrangi, Shashi Ravi Suman (2015) Drug-cyclodextrin complexes: an approach to enhance the solubility and dissolution properties of poorly soluble drugs. PhD thesis, University of Greenwich.
|
PDF
Shashi Ravi Suman Rudrangi 2015.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (21MB) | Preview |
Abstract
The main objective of this study was to investigate different manufacturing processes claimed to promote inclusion complexation between different drugs and cyclodextrins (econazole and α-cyclodextrin; indomethacin and methyl-β-cyclodextrin; olanzapine and methyl-β-cyclodextrin; flurbiprofen and methyl-β-cyclodextrin) in order to enhance the apparent solubility and dissolution properties of drugs. Specifically, the effectiveness of supercritical carbon dioxide processing for the preparation of solid drug-cyclodextrin inclusion complexes was investigated and compared to other preparation methods. Nitrate, besylate, sulfosalicylate dihydrate and maleate salts of econazole were synthesised. The solid drug-cyclodextrin inclusion complexes were prepared by physical mixing, freeze drying from aqueous solution and processing with supercritical carbon dioxide. The complexes were evaluated by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, 1H-nuclear magnetic resonance (nuclear Overhauser effect correlation spectroscopy and inversion recovery T1 measurement experiments), and dissolution rate studies. Inclusion yield (%) studies of econazole base into α- and methyl-β-cyclodextrin were conducted in supercritical carbon dioxide to investigate the influence of pressure, temperature and contact time on the inclusion. All the working parameters (pressure, temperature and contact time) played a significant role in the inclusion of econazole base into cyclodextrins. Isothermal titration calorimetric studies of econazole besylate and sulfosalicylate dihydrate salts and α-cyclodextrin confirmed the formation of complexes between the salts and α-cyclodextrin in a 1:1 stoichiometry. Different degrees of crystallinity were observed in the analyses of products prepared by various methods, suggesting the possibility of drug-cyclodextrin interactions of different efficiencies, which may give rise to different degrees of inclusion formation and/or crystallinity of the sample. Nevertheless, products obtained by the freeze-drying and supercritical carbon dioxide-inclusion methods were among the ones showing the highest interaction between the drug and the cyclodextrin. All systems based on α-cyclodextrin and methyl-β-cyclodextrin exhibited greater drug release profiles than the drug alone. Solid state complexation using supercritical carbon dioxide processing proved to be useful complexation method for econazole and its salts into α-cyclodextrin; indomethacin, olanzapine and flurbiprofen into methyl-β-cyclodextrin. The freeze drying method produced highly amorphous and rapid dissolving complexes; however, it was characterised by long, energy-intensive processing steps. Supercritical carbon dioxide inclusion method was shown to be an efficient approach for the preparation of solid-state inclusion complexes. It is an efficient and economic process that allows the formation of solid complexes based in strong intermolecular forces in high yield in a single step avoiding the use of organic solvents and the problems associated with their residues.
Item Type: | Thesis (PhD) |
---|---|
Uncontrolled Keywords: | Cyclodextrins; fluid technology; physiological chemistry; |
Subjects: | Q Science > QD Chemistry |
Faculty / School / Research Centre / Research Group: | Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI) |
Last Modified: | 23 Nov 2017 17:43 |
URI: | http://gala.gre.ac.uk/id/eprint/18143 |
Actions (login required)
View Item |
Downloads
Downloads per month over past year