Iontophoresis mediated topical delivery of dermatologically relevant small molecules

Purpose. The aim of this dissertation was to evaluate iontophoresis as a potential enhancement method for the topical delivery of antibacterials and corticosteroids across hairless rat skin. Also, thermal enhancement of transdermal drug permeation in conjunction with enhancement techniques like iontophoresis and microporation was investigated.;Methods. In vitro studies were performed using excised hairless rat skin mounted on Franz diffusion cells. Drug candidates employed in this project were Dexamethasone sodium phosphate (DEX), Triamcinolone acetonide (TMCA) and Tetracycline hydrochloride (TTC). Cathodal and anodal iontophoresis were performed depending on the ionic state of the drug in the donor. Samples taken were analyzed by HPLC. In vivo studies were performed on anaesthetized hairless rats. Tape stripping was performed after iontophoresis and the underlying skin was excised and accounted for the amount of drug deposited. Transepidermal water loss (TEWL) was measured to confirm the removal of stratum corneum. Microdialysis was performed in vivo to determine the concentration of drugs in the dermis.;To study the effect of heat on transdermal permeation of drugs, in vitro studies were performed as described above at 37°C and 41°C in conjunction with iontophoresis and microporation.;Results. In vitro results showed six fold and seven fold enhancement of transdermal permeation for both DEX and TTC by iontophoresis compared to passive controls and anodal iontophoresis. No enhancement was evident for transdermal permeation of TMCA by iontophoresis.;Iontophoresis resulted in accumulation of twice the amount of DEX and TMCA in the stratum corneum by iontophoresis compared to passive delivery. Skin extraction substantiated the enhancement effect of iontophoresis in vivo. In vivo microdialysis demonstrated the effect of partition coefficient on the recovery and dermal levels of drugs.;Increasing the temperature by 4°C showed a two fold enhancement for the percutaneous permeation levels of DEX and TTC. Thermal enhancement with iontophoresis and microporation decreased the lag time of drug release by approximately two times. The release rates and permeability coefficient values indicate the formation of a DEX depot in the skin.;Conclusion. In vitro studies revealed that iontophoresis significantly enhanced the permeation of dexamethasone sodium phosphate and tetracycline hydrochloride across hairless rat skin but had no effect on the permeation of triamcinolone acetonide. In vivo results demonstrated significant deposition of DEX and TMCA in the stratum corneum and underlying skin by iontophoresis. In addition it was shown that DEX forms a depot in the stratum corneum of skin which is retained for 48h. Transdermal permeation of DEX and TTC was also affected by increase in temperature.