Muco-Adhesive Liquid Ophthalmic Vehicles - Evaluation of Macromolecular Ionic Complexes of Pilocarpine

Abstract

Pilocarpine (Pi), a widely used anti-glaucoma drug, is characterized by a very low bioavailability, due to poor corneal penetration and extensive precorneal loss. Purpose of the present study was the preparation and “in vivo” evaluation of a series of liquid formulations containing salts (or ionic complexes) of Pi with soluble polyanionic polymers of natural, synthetic or semi-synthetic origin. It was speculated that since to some of the polymers have been attributed muco-adhesive properties, they might favour the preocular retention of the ionically bound drug, and enhance its bioavailability. The polymers submitted to investigation were a) hyaluronic acid (HA); b) poly-(galacturonic acid) (PGA); c) Mesoglycan (MG, a complex mixture of mucopolysaccharides); d) Carboxymethylchitin (CMCh) and d) two poly(acrylic acids) of different molecular weight (PAA1 and PAA2). Aqueous solutions of the Pi polymer salts, each containing 1.53% w/w Pi base (equivalent to 2.0% Pi nitrate) were tested for miotic activity in albino rabbits, using as reference an aqueous, 2% solution of Pi nitrate, either as such or viscosized with 1.5 and 5.0% poly(vinyl alcohol), (PVA). All polymeric solutions enhanced, in some cases to a statistically significant extent, the bioavailability of the drug with respect to the reference solutions. The relevance of viscosity effects, and of possible muco-adhesive phenomena to the bioavailability of Pi from the salt-vehicles are discussed