Prostaglandin-releasing hydrogels for peptic ulcer disease

An oral polymeric drug delivery system for the release of prostaglandin F2alph (PGF2alph) is developed fro the induction of cytoprotection. Prostaglandins, in doses one-tenth that of amounts that cause adverse effects, induce the mucosa to be reinforced against ulcerogenic stimuli. The polymeric materials used are hydrogel copolymers of 2-hydroxyethyl methacrylate (HEMA) and related comonomers or HEMA and poly(tetramethylene oxide). When the copolymer discs are placed in prostaglandin hydroalcoholic solutions, the swelling hydrogel absorbs drug along with the solvent into the polymer network. Evaporation of solvent leaves drug trapped within a dried hydrogel matarix. Quantitation of drug payloads show maximal drug loading in the range of 0.1 to 1.1 % dried hydrogel weight occurring after 8 to 12 hours absorption time. Upon exposure to aqueous media, release of prostaglandin from the hydrogel is in response to dissolution of the drug by a advancing solvent front. Release profiles show an initial lag time possible due to the slow rate of release media flow through the in vitro system. Use of an agitation-type system decreases the lag time seen significantly. The lag time can be obviated by ionically bonding prostaglandin carboxylate anion to a charged quaternary ammonium hydrogel surface. Exposure to simulated gastric fluid causes immediate release of prostaglandin from the surface of up to 3 mg drug in four hours. Release of prostaglandin entrapped within the hydrogel matrix ranges from 5-30% of initial drug payload in the initial four hour period. In vivo release of prostaglandin from hydrogel rods is studied by introducing loaded, dried rods into Dprague-Dawley rats. Drug release of 38% of initial payload occurs in five hours and 67% of initial payload in a eight hour period, similar to results found in vitro rod studies. The results obtained from swelling-loaded and surface-loaded prostaglandin experiments will provide insight into development of an oral hydrogel prostaglandin-releasing delivery system for in vivo induction of cytoprotection utilizing minimum amounts of prostaglandin.