Effect of Formulation Factors on In Vitro Permeation of Diclofenac from Experimental and Marketed Aqueous Eye Drops through Excised Goat Cornea

抄録

  The effect of formulation factors on permeation of diclofenac from some experimental and marketed aqueous eye drops through excised goat cornea was evaluated. Raising the pH of formulation from 6.0 to 8.0 or diclofenac concentration from 0.05 to 0.15% (w/v) or adjusting tonicity with mannitol or addition of viscolizing agent decreased apparent permeability coefficient (Papp). Formulation (pH 7.4) containing sodium metabisulfite or EDTA or combination of methyl and propyl paraben showed significantly (p<0.05) higher Papp whereas benzalkonium chloride (BAC) had no effect and sorbic acid (SA) had reduced permeation. Surprisingly marketed drops containing BAC or SA, showed significantly (p<0.05) higher Papp and decreased in the order of Difen>Voveran>NSAID>Dicol>Diclolab. Lower pH (7.1-7.3) and surface tension of drops indicating presence of surfactant, could mediate increased permeation and presence of buffer could cause irritation on in vivo instillation. The marketed formulations showed corneal hydration >83% suggesting corneal damaging potential.