This thesis investigated the possible use of transdermal iontophoresis in paediatric care, as an alternative strategy to the oral and intravenous routes. More specifically, the potential for non-invasive delivery of ranitidine, midazolam, and phenobarbital; and the clinical sampling of iohexol through the skin were examined. The feasibility for monitoring kidney function was assessed in vitro and in vivo using the glomerular filtration rate (GFR) marker, iohexol. Sampling of iohexol in vitro was sensitive to the changes in its subdermal concentration, and pharmacokinetic parameters estimated from skin sampling agreed well with reference subdermal values. Similar observations were confirmed in vivo in a pilot study performed in four children undergoing routine iohexol GFR test. Iontophoresis was well tolerated in all subjects and the marker was successfully extracted through the skin. In 3 of 4 subjects, the elimination rate constant estimated from skin sampling data agreed well with blood sampling results. This study demonstrated the potential of transdermal iontophoresis as a non-invasive sampling approach which could significantly improve the quality-of-life of children. Drug delivery by transdermal iontophoresis was examined in vitro for three commonly used paediatric medicaments: ranitidine, midazolam, and phenobarbital. Experiments used both intact and compromised pig skin to model the less resistant skin of premature babies. Iontophoretic delivery across intact skin was superior than passive delivery and optimised conditions were achieved by use of maximal molar fraction of the drug, higher current intensity, and appropriate vehicle pH. Pluronic® F-127 gels were suitable drug matrices for the iontophoretic delivery of ranitidine. Midazolam and phenobarbital transdermal delivery through partially compromised skin barriers was controlled by iontophoresis. Across highly compromised skin, however, passive diffusion increased drastically and iontophoretic control was lost. Overall, it was possible to deliver therapeutically meaningful fluxes of all three drugs with acceptable patch application area.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:512312 |
| Date | January 2009 |
| Creators | Djabri, Asma |
| Contributors | Guy, Richard ; Delgado-Charro, Maria |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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