Electrochemical Methods for Drug Characterisation and Transdermal Delivery : Capillary Zone Electrophoresis, Conductometry, and Iontophoresis

• Main Author: Merclin, Nadia
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Institutionen för farmaci 2003
• Subjects: Pharmaceutical chemistry; Capillary zone electrophoresis; precision conductometry; iontophoresis; passive diffusion; lidocaine; ALA; ALA-ester derivatives; sponge phase; carbopol gel; Farmaceutisk kemi
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3774; http://nbn-resolving.de/urn:isbn:91-554-5803-3

This thesis concerns the development and utilisation of techniques for characterisation and transdermal delivery of various systems for pharmaceutical applications. The degree of dissociation of drug molecules and the mobilities of the different species formed are essential factors affecting the rate of drug delivery by iontophoresis. Hence, determination of drug mobility parameters and equilibrium constants are important for the development of iontophoretic systems. With capillary zone electrophoresis using a partial filling technique and methyl-β-cyclodextrin as chiral selector, the enantiomers of orciprenaline were separated. The association constants between the enantiomers of the drug and the selector were also evaluated. Precision conductometry studies were performed for the hydrochloride salts of lidocaine and 5-aminolevulinic acid in aqueous propylene glycol and water as media, respectively. Iontophoresis is a technique for drug delivery where charged molecules are transported into and through skin by application of a weak direct electrical current. The drugs 5-aminolevulinic acid and its methyl ester were used as model compounds and incorporated in two different drug delivery vehicles, a sponge phase and carbopol gel. The bicontinuous structure of the sponge phase, constituted of monoolein and a mixture of propylene glycol and water, makes it interesting for use in iontophoretic delivery, since ions can move more or less freely in the aqueous as well as in the lipid domains. Furthermore, all three components are known for their penetration enhancing abilities. Hydrogels like carbopol gels are interesting media with respect to iontophoretic studies, since devices for iontophoresis often utilize hydrogels as contact interfaces between the skin and the electrodes. The results indicate that the transport achieved iontophoretically using the gel (1 % active substance) was comparable with the passive delivery of clinically used formulations (16 % - 20 % active substance).