1 The essential features and mode of action of oral osmotic drug delivery systems (Oros®) for metoprolol fumarate and oxprenolol succinate are described. 2 Critical aspects in the development of systems for once-daily administration of both drugs are discussed, and methods for evaluating in vitro release characteristics are presented. 3 In vitro testing confirmed that drug delivery corresponded closely to the theoretical release behaviour predicted from the physicochemical and membrane permeability characteristics for both oxprenolol and metoprolol systems. 4 In vitro release rates were also shown to be unaffected by pH, in vitro test procedures, dissolution media and long-term storage at different temperatures.

We applied drugs in aqueous gels to the buccal mucosae of normal volunteers to develop an assay of gastrointestinal irritation potential. We studied effects of pH, concentrations, and formulations. We evaluated irritation by subjects' reports of their sensations and observers' grading of visible reactions. On an irritation log ranking scaled 0 to 5, placebo gels produced virtually no irritation, except those formulated at pH 1, 2, and 14. Albuterol, furosemide, and methyldopa produced essentially no irritation. Minutes of exposure to sodium indomethacin, sodium naproxen, and propranolol (at, respectively, pH 8.2, 9.6, and 4.8 and concentrations of 12%, 40%, and 8%) caused ulceration that took up to weeks to heal. Acid forms of naproxen and indomethacin caused minimal or no irritation. Although irritation models based on one gastrointestinal area have limitations, our results indicate that the minimally invasive buccal assay allows ranking of contact irritation potential of drugs and formulations that could aid in selecting optimum formulations for clinical use.