In-vitro and in-vivo evaluation of ocular delivery of diclofenac sodium from ophthalmic solutions and gel

Diclofenac sodium is successfully used in the treatment of ophthalmic disorders.  Diclofenac sodium (0.1​% w​/v)​, was formulated in various viscous solns. and gels in order to modulate the release of the drug and thereby, achieve controlled drug delivery for topical ophthalmic application.  The polymer utilized to prep. the viscous solns. and gel was Pluronic F 127 (Poloxamer 407)​.  The rheol. behavior of the prepns. was studied and showed pseudoplastic flow characteristics at high polymer concns.  The IR spectra and DSC anal. for the drug, Poloxamer and phys. mixt. (1:1, drug:polymer ratio) were investigated and the results obtained revealed that, there is no interaction between the drug and the utilized polymer.  The in-​vitro release of the drug, from the prepd. formulations into a simulating tear fluid, were carried out by adopting the dialysis method.  As the concn. of the polymer increases the amt. of drug released was progressively decreased and the release profile followed Higuchi diffusion mechanism.  The effect of diclofenac sodium formulations (viscous solns., gel and Vltaren eye drops) on the healing rate of ulcerative cornea of rabbits were studied.  The statistical anal. of the in-​vivo data revealed that, the viscosity of the system dictates the in-​vivo performance of the drug only within narrow and low range i.e. 5-​15 cP.  The in-​vivo study also, revealed that Poloxamer enhances, drastically, the drug healing rate of ulcerative cornea of rabbits.  Poloxamer recovered the lethally heat-​shocked fibroblast and acted as a non ionic surfactant offering means of enhancing drug permeation through the cornea.  Also, Poloxamer acts as viscosity imparting agent which lead to increase in drug contact time with the ulcerative cornea.