Formulation and Evaluation of Therapeutic Contact Lenses for Ophthlmic drug delivery

Abstract

Glaucoma is a chronic disease currently treated with high dose frequent instillation of eye drops. Fixed combination of bimatoprost/timolol eye drop solution is used to newlinemanage elevated intraocular pressure in the glaucoma patients, including the individuals who are uncontrolled by the monotherapy. Generally, higher doses of eye newlinedrop solutions are given, due to its poor ocular bioavailability, which leads to hyperaemia and systemic cardiac side effects. Here, we introduce multiple implantsladen newlinecontact lens (IM) to deliver timolol, bimatoprost and hyaluronic acid (HA) at the therapeutically relevant doses without high burst release. The drug-loaded implants newlinewere individually implanted in the outer periphery of the silicon contact lenses. newlineAtomic force microscopy report showed a smooth surface of the implant contact lens, as the implants were within/inside the contact lens matrix. The implant lens (IM) newlineshowed major loss of drugs [timolol = 51.74 and#956;g (60.6 %), bimatoprost = 31.38 and#956;g (61.75 %) and HA = 12.04 and#956;g (46.03 %)] during the monomer extraction and wet sterilization, newlinewhile the option of dry radiation sterilization (IM-R lens) and hydration for 24 h prior to use showed relatively lesser loss of drugs [timolol = 14.40 and#956;g (16.87 %), bimatoprost newline= 24.42 and#956;g (47.95 %) and HA = 6.43 and#956;g (24.41 %)]. The in vitro drug release data of IMR lens, showed sustained release for 72 h, with low burst release in comparison to the newlinesoaked (SM) and direct drugs-laden contact lenses (DL). The in vivo drug release data in the rabbit tear fluid showed sustained release using IM-R lens in comparison to the newlineSM lens and eye drop therapy. The burst release with the IM-R lens was many folds reduced, which could bypass the side effects associated with the multiple eye drop newlinetherapy. The in vivo pharmacodynamic study in the rabbit model showed peak and valley profile with multiple eye drop therapy. In contrast, IM-R lens prolongs reduction newlinein the intraocular pressure (IOP) for 120 h.