Intravitreal Implantable Film Containing Ketorolac Tromethamine Microsponges – In Vitro/In Vivo Correlation

Abstract

This research involved preparation, optimization, in vitro and in vivo evaluation of Ketorolac Tromethamine (KT) from the implantable film containing KT-microsponges to be inserted at the posterior part of the eye and may treat some complicated conditions such as cystoid macular edema (CME) and/or diabetic macular edema (DME). Specific amount of our previously prepared KT microsponges (equivalent to 6 mg KT) was added to a film base composed of poly vinyl alcohol (PVA) and glycerol to which 3 mg uncoated (pure) KT added then casting the combination to get film (0.6 cm × 0.3 cm). The prepared film was evaluated for weight uniformity, thickness, folding endurance, surface pH and the percentage of moisture absorption (PMA) and percentage moisture loss (PML) as well as in vitro release and in vivo tests. The obtained film showed average weight (8.87mg ± 0.2) with variation less than (5%), thickness (0.3 cm ± 0.04), surface pH ranged (7-7.3), folding endurance more than (300) times indicating excellent elasticity with good integrity through measuring percentage moisture absorption (PMA) and percentage moisture loss (PML). The in vitro release showed biphasic release where 40% of the drug was released within the first day (initial phase) followed by sustained release continued to give 90% of the drug within 3 months. The in vivo test showed that the implanted film in the vitreous chamber of the rabbit eye had good ant-inflammatory properties against acute and chronic inflammation as well as prevent recurrent inflammation. The work succeeded to prepare KT film containing microsponges to be implanted intravitreally at the posterior chamber of the eye and suggested to treat complicated condition including postoperative cystoid macular edema as well as diabetic macular edema as alternative to repeated intravitreal KT injections, so decreasing side effects with improved patient compliance.