Ophthalmic antioxidant activity of a model antianginal drug using corneal hydrogel formulation: Effect of carboxymethyl starch on physicomechanical behaviour and release/permeation kinetics.

Trimetazidine (TIZ), a model antianginal drug helps reducing the formation of free radicals. Carboxymethyl starch (CMS) is acknowledged to improve mucoadhesion, flexibility and strength in combination with hydroxypropyl methylcellulose (HPMC) compared to HPMC alone. Ocular antioxidant activity of trimetazidine hydrogel has been undertaken after topical application. Effect of CMS on physicomechanical performance and release/permeation kinetics was also studied. HPMC based hydrogel was prepared in different combination with CMS. Carrageenan induced rat eyeball was extracted for histological analysis and malondialdehyde assay. Presence of CMS significantly increased viscosity, and also improved hardness, adhesive force, adhesiveness, and cohesiveness compared to its absence of the hydrogel. Carboxymethyl group of the CMS increased hydrophilicity, hydration and swelling property of the hydrogel. TIZ hydrogel presented organized and prolonged diffusion controlled drug release through the cornea for around 9 h. The histology of rat eye revealed that, the ganglionic layer damage in retina has been reduced prominently in the TIZ hydrogel treated group. Flexible docking studies demonstrated a stronger binding interaction between TIZ and IL-1β (-5.4 kJ/mol) compared to diclofenac (-4.68 kJ/mol) and dexamethasone (-5.33 kJ/mol). Trimetazidine hydrogel could be used for controlled ophthalmic antioxidant activity after topical application. Presence of CMS improved physicomechanical performance.