Drug in adhesive patch of palonosetron: Effect of pressure sensitive adhesive on drug skin permeation and in vitro-in vivo correlation

Abstract

Palonosetron (PAL) is recommended for the prevention of chemotherapy-induced nausea and vomiting. The aim of this study was to develop a long-acting PAL transdermal patch to improve patient compliance. We were particularly concerned about the effect of pressure sensitive adhesives (PSAs) on PAL skin permeability. Formulation factors including PSAs, backing films and drug loadings were investigated in the in vitro skin permeation study using rabbit skin. Fourier transform infrared spectrometer study and thermal analysis were conducted to investigate the drug-PSA interaction and thermodynamic activity of PSAs, respectively. The results indicated that high drug skin permeation amount was obtained in PSA DURO-TAK®87-2516, which had low interaction potential with PAL and high thermodynamic activity. The optimized patch was composed of PAL of 8 %, DURO-TAK®87-2516 as PSA, CoTran™ 9700 as backing film and Scotchpak™ 9744 as release liner. The in vitro skin permeation amount of the optimized patch was 734.0±55.8μg/cm2 during 3-day administration. The absolute bioavailability of the optimized patch was 43 % in rabbit and a good in vitro-in vivo correlation coefficient was obtained (R2=0.989). These results indicated the feasibility of PAL transdermal patch in the prevention of chemotherapy-induced nausea and vomiting.