Effect of Preservatives on Systemic Delivery of Insulin by Ocular Instillation in Rabbits

Abstract

The effects of absorption promoters and ophthalmic preservatives on the systemic absorption of insulin through the ocular route were investigated in albino rabbits. Insulin absorption was evaluated by its hypoglycaemic response. Although ocular instillation of insulin alone did not decrease the serum glucose concentration, instillation of insulin with absorption promoters such as EDTA and saponin decreased it. The promoting effect depended on the concentration of the absorption promoters. Of ophthalmic preservatives investigated (benzalkonium chloride, paraben, 2-phenylethanol, benzyl alcohol and sorbic acid), benzalkonium, chloride and paraben showed promoting effects. The promoting effect for benzalkonium chloride was reversible and dependent on concentration of both benzalkonium chloride and insulin in the formulation.

Electrophysiological Characterization of Tight Junctional Pathway of Rabbit Cornea Treated with Ophthalmic Ingredients

“…They were previously reported to be effective for the corneal penetration of various drugs at those concentrations without severe toxicity. 6,7,13,17) The ingredients decreased TEER. The electrophysiological method enables evaluation of the change of the paracellular pathway transiently.…”

“…Newton et al 5) reported that Azone, a transdermal absorption enhancer, increased the ocular delivery of instilled cyclosporine and enhanced immunosuppression activity. We previously reported that ocular absorption of insulin was increased by ethylenediaminetetraacetic acid (EDTA) and benzalkonium chloride (BK), 6) and corneal penetration of sorbitol was improved by EDTA and chlorhexidine acetate. 7) The paracellular pathway can be monitored in real time by continuous measurement of the electrophysiological property of the cornea.…”

Effect of Brij-78 on Systemic Delivery of Insulin from an Ocular Device

“…The pharmaceutical aspects of these eyedrops, such as the absorption site for insulin, 1 the role of absorption enhancers, [1][2][3][4][5][6][7][8][9][10] and the correlation between its pharmacokinetics and pharmacodynamics, 1,10 have been well established. The latter allows scientists to easily quantitate the release of insulin by monitoring the changes in blood glucose levels.…”

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

“…Combination of MP and PP has been reported to enhance the corneal permeation of insulin, a peptide. 19) SMS is used as antioxidant and has also got preservative action. Addition of SMS or EDTA to diclofenac ophthalmic solution 0.1％ (w /v) was also found to signiˆcantly increase the permeation.…”