Reduction of cardiovascular side effects associated with ocular administration of metipranolol by inclusion in...

A new formulation of metipranolol base for ophthalmic administration was developed consisting of a colloidal suspension of polyepsiloncaprolactone nanocapsules with an oily core (Migliol 840) in which the drug is dissolved. Physicochemical properties of the nanocapsules show that the polymer coating around the oily droplets causes an important reduction of the droplet size, with no significant modification of the surface charge noted. When this formulation was administered to rabbits, a reduction of intraocular pressure similar to that seen with commercial eye drops was observed. Nevertheless, the evaluation of the cardiovascular side effects clearly showed lower conjunctival absorption of the encapsulated drug compared with the commercial drops. The direct (bradycardia) and the indirect evaluation (based on the study of the influence on the hypotensive and positive chronotropic effects of isoprenaline) showed that blockage of beta-adrenoreceptors was reduced greatly by the topical administration of the new formulation.