Insoluble ionic complexes of polyacrylic acid with a cationic drug for useas a mucoadhesive, ophthalmic drug delivery system

We have developed a new mucoadhesive drug delivery formulation based on an ionic complex of partially neutralized poly(acrylic acid) (PAA) and a highl y potent beta blocker drug, levobetaxolol . hydrochloride (LB . HCl), for u se in the treatment of glaucoma. PAA was neutralized with sodium hydroxide to varying degrees of neutralization, Aqueous solutions containing concentr ations of LB . HCl equivalent to the degree of PAA neutralization were adde d to the PAA solutions and formed insoluble complexes, which were isolated. The complex formation was followed by turbidimetric titration, and the com plexes were characterized by IR and H-1 NMR spectroscopy. Complexes were pr epared with varying degrees of drug loading, such that the same PAA chain w ould have free -COOH groups for mucoadhesion along with ionic complexes of LB .H+ with COO- groups. Thin films of the complexes dissociated to release the drug by ion exchange with synthetic tear fluid. The films shrunk conti nuously during release of the drug and dissolved completely in 1 h. Solid i nserts of these films could be useful as a mucoadhesive ophthalmic drug del ivery system.