Skin permeation of gemcitabine hydrochloride by passive diffusion, iontophoresis and sonophoresis: In vitro and in vivo evaluations

Abstract The present study was undertaken to assess skin permeation of gemcitabine hydrochloride (GEM) following passive diffusion, iontophoresis and sonophoresis. In vitro passive diffusion were carried out in HEPES solution of pH 4.5, 5.8, 7.4 and 9.2 which revealed a pH-dependent permeation of GEM. Further, cathodic and anodic iontophoresis were carried out and the results indicated that anodic iontophoresis exhibited highest amount of GEM permeated at the end of 6 h (Q 6h  = 2203.74 ± 128.75 μg/cm 2 ). Subsequently, effect of varying drug concentration on the permeation of GEM with iontophoresis was studied. The results demonstrated that GEM exhibited a concentration-dependent permeation profile with the highest permeation observed at 50 mg/mL (Q 6h  = 3334.94 ± 133.38 μg/cm 2 ). In sonophoresis, among the different amplitudes tested, highest skin permeation of GEM was observed at 40 W amplitude. Also, effect of sonophoresis on varying drug concentrations revealed that highest permeation of GEM was observed at 50 mg/mL (Q 30min  = 950.24 ± 38.61 μg/cm 2 ). In vivo permeation studies carried out using passive diffusion, anodic iontophoresis or sonophoresis indicated that anodic iontophoresis of GEM showed a higher plasma concentration (2472.83 ± 90.91 ng/mL) as compared to sonophoresis (2198.27 ± 109.91 ng/mL) and passive diffusion (845.21 ± 52.70 ng/mL). This study illustrates the application of iontophoresis or sonophoresis as a non-invasive drug delivery modality for GEM.