Lopinavir metered-dose transdermal spray through microporated skin: Permeation enhancement to achieve therapeutic needs

摘要

A user friendly metered-dose transdermal spray (MDTS) of Lopinavir was developed and a combination of chemical and physical penetration enhancement techniques was utilized to enhance overall drug permeation across skin. Formulation was optimized varying Kollidon? VA 64 level while optimized batch was exhaustively characterized for in vitro drug release, ex vivo skin permeation and in vivo bioavail-ability. Safety and stability were also ascertained. Formulation containing 5 %w/v of Kollidon? had best sprayability and volatilization property. A significantly high permeation enhancement ratio (1.77) and steady state transdermal flux (52.5 ug/cm2/h) through microporated pig ear skin ex vivo indicated the permeation enhancement potential of the techniques applied. A remarkable 3-fold rise in relative bioavailability via transdermal route (Fmdts via microporated skin = 291.15%) as compared to oral suspension of marketed tablet (AUCo-?> = 45.94 h*ug/ml) further confirmed the validity of our hypothesis. The outcomes of in vitro, ex vivo and in vivo characterization of Lopinavir MDTS represented the system as safe, effective and stable which seems promising for their extended clinical evaluation.