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Studies of Drug-Surfactant Interactions

Patel, Rajesh; (2000) Studies of Drug-Surfactant Interactions. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Dissolution is commonly the rate limiting step to the absorption of poorly water-soluble drugs. Surfactants can be used to improve the dissolution rate and thus enhance the bioavailability of such drugs. In this thesis, the possible effects of a series of ionic and nonionic surfactants on the solubility and dissolution rate of a poorly water-soluble drug simvastatin were studied. The emphasis of this thesis has been to study drug surfactant interactions from a mechanistic perspective, and therefore improve the understanding of how surfactants affect the dissolution rate of poorly water-soluble drugs. The first part of the work involves studying the dissolution and solubility of simvastatin in a series of surfactants. In the next section surface energy studies on both the drug and surfactant were conducted. It was shown that there was a correlation between the increase in solubility and the free energy of interaction between the drug and surfactant. Dynamic surface tension data were collected and used to explain anomalies in the apparent diffusion coefficients between the ionic surfactants and nonionic surfactants. It was shown that an electrical barrier impeded the adsorption of ionic surfactants to the drug surface. Subsequently, the dissolution rate corrected for solubility was lower in the presence of ionic surfactants. In addition purity effects of surfactant were found not to affect the solubility, but influenced the dissolution rate. This was due to the slower adsorption of impure surfactant to the simvastatin surface. Isothermal microcalorimetry was used as a tool to study the thermodynamics of interaction between the drug and the surfactants. It was also found that small deviations from ideal solution behaviour could be detected using this method. Overall the study confirms that macroscopic observations such as dissolution and solubility can be interpreted more fully by utilising molecular arguments derived from surface energetics, thermodynamics and adsorption dynamics.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies of Drug-Surfactant Interactions
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10116676
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