Development of Transdermal Delivery System of Dexamethasone, Palonosetron and Aprepitant for Combination Antiemetic Therapy

Purpose: The objective of this study was to assess the possible transdermal delivery for combination antiemetic therapy of dexamethasone, palonosetron and aprepitant, commonly prescribed in chemotherapy induced nausea and vomiting. Methods: Pluronic lecithin organogel formulation was optimized to incorporate all the three drugs. The influence of formulation parameters like drug concentration (1-5% w/w) and permeation enhancers (oleic acid, n-methyl-2-pyrrolidone, propylene glycol and polyethylene glycol 400) on the transdermal delivery of selected antiemetic agents were evaluated ex vivo. Results: Drug release profiles of dexamethasone, palonosetron and aprepitant from the gels were distinct and biphasic in nature. Higher permeability coefficient was observed in palonosetron, average in dexamethasone and was least in aprepitant. Proportional enhancement in the transdermal fluxes of all the three actives were observed with increase in drug concentrations studied. The highest drug concentrations were further treated with different chemical skin enhancers, which improved (1.2-3.3 folds) the permeability coefficient of actives, but not to the same extent. Greater flux values were observed with oleic acid (for dexamethasone) and propylene glycol (for palonosetron and aprepitant). Concomitant transdermal delivery reduced the flux values (P<0.001) of dexamethasone (9.82 ± 1.39 µg/cm2/h), palonosetron (21.36 ± 1.95 µg/cm2/h) and aprepitant (5.04 ± 0.62 µg/cm2/h), compared to their corresponding values when evaluated individually. Conclusion: This study conclude that the optimized pluronic lecithin organogel could be utilized for the simultaneous transdermal delivery of dexamethasone, palonosetron and aprepitant, which need to be proved further in vivo.