The broad long-term goal of this research is to reduce morbidity due to arthritis by developing injectable long term intra-articular drug delivery systems. Intra-articular steroids have been a mainstay of treatment for arthritis for more than 50 years. For many patients multiple injections are necessary [1], and the longer acting the steroid the more effective it is [2][3-5]. We have developed a series of steroid delivery systems which can deliver fluocinolone or dexamethasone at therapeutic levels in the eye for as long as 3 years from a single implantation [6, 7]. These delivery systems have been extensively tested in animal models and have completed Phase III clinical testing in patients with ocular inflammatory disease. We believe that the development of an injectable intra-articular sustained release steroid delivery formulation is readily achievable and that this device will become a useful tool in the treatment of rheumatoid arthritis. The specific aims of this proposal are to: 1, formulate sustained release suspensions for rimexolone; 2, test the in vitro release characteristics of these formulations into buffer; and 3, test the in vivo pharmacokinetics and the safety of the formulations in the sheep. The team of investigators is expert in polymer chemistry, pharmacokinetics and drug development. The Vitrasert(r) implant for the treatment of AIDS-related CMV retinitis was developed in the lab of the Principal Investigator of this proposal and we have successfully developed a nevirapine implant under SBIR grant program R43HD036548-01, R44AI047788-02 & R44AI047788-03: The Prevention of Vertical HIV Transmission. The successful completion of this project will lead rapidly to the development of an injectable dosage form that could ideally deliver continuous antiviral blood levels. The successful completion of these specific aims will constitute a readily identifiable milestone which will permit us to continue with Phase 2 of this proposal where we will test the efficacy of the devices in animal models of arthritis and complete the requisite laboratory work to apply for an Investigational New Drug Exemption from the FDA.