Experimental studies on the application of iontophoresis method

It was aimed to increase the permeation of sildenafil through skin effectively, controlled by iontophoresis. The UV and IR spectrums were first evaluated, Solubility values (0.088 to 2.041 mg/ml) and octanol water partition coefficients (- 1,293 to -1,272) of sildenafil citrate were determined for the pH range of 2 to 8. The permeation properties of sildenafil through various membranes were then investigated using Franz type diffusion cells. As a result, the permeability coefficients were found to be with the following order: dialysis membrane>PDMS membrane>rabbit skin>human skin (log k values: -1,135>-2,694>-2,982>-2,995 cm/h respectively). When iontophoresis experiments were conducted, higher permeation values were observed for all membrane types. In PDMS m embrane experiments, higher permeations were observed when higher amounts of NaCI were employed to the donor phase. This observation was an evidence for the mechanism of sildenafil penetration to b e a ctive iontophophoretic transport. This was also suggested that the presence of CI" ion at the donor chamber (anode) was necessary when Ag/AgCI electrodes were used for iontophoresis experiments. The penetrations of sildenafil through different skin layers were also investigated and the stratum corneum layer was found to be the main barrier. The gel formulation of sildenafil was also developed comprising transkutol, hidroxypropil cellulose, propylene glycol and NaCI and it was applied to the dorsal part of rabbit skin. A constant electric c urrent ( 0.5 m A/cm2) (iontophoresis) was applied and blood sildenafil contents were analysed by HPLC and results of iontophoresis experiments were compared with passive penetration and sildenafil blood p rofiles a fter o rai s ildenafil a dministration. When c onstant e lectric c urrents (iontophoresis) were employed, higher AUC and Cmax. values were obtained (AUCi0ntophoresis=80,950 ug/ml.min.; AUCpassive=15,013 um/ml.min.; A UCorai= 15.634 ug/ml.min; Cmax.iontoPhoresis=0,620ug/ml.; Cmax.passive=0,166 ug/ml.; Cmax.Orai=0,082 ug/ml.). The possibility of the different usage or application of the iontophoresis was investigated at the other part of the study. The electroforetic mobility of the urea159 molecule was first established in this study and the effective and controlled delivery of the urea molecule was demonstrated during in-vitro hemodialysis experiment by iontophoresis. Similarly, the determination/prediction of the blood urea level was achived after extracting the urea from the body through skin by reverse iontophoresis. There was a very good correlation found between real blood urea levels and extracted urea levels from the skin by iontophoresis when adult patients were used with renal insufficiency (87.8% - &99.1%). The developed method was also applied to t he pediatric patients with end stage renal failure. Similarly their blood urea levels were successfully predicted before and after they received the hemodialysis. The same method was also used to determine blood lithium levels of the psychiatric patients who have been receiving lithium and there was a correlation found between blood lithium levels and extracted lithium levels from the skin by iontophoresis. As a result, rabbit skin was found to be a suitable model for sildenafil penetration experiments by presenting similar permeability values with human skin. Iontophoresis was found to be a very useful technique and method to increase sildenafil penetration through skin; to remove undesired substances from the blood during hemodialysis and to predict and determine the blood levels of some substances like urea and lithium by applying reverse iontophoresis as it was demonstrated.