This thesis describes in vitro and in vivo evaluation of a gastric retention formulation (GRF) developed at Oregon State University. The formulation was prepared from xanthan gum and locust bean gum as gelling agents and other formulation ingredients were added, then it was originally vacuum oven dried. The effect of freeze drying on GRF was studied in this research. Freeze dried GRF were evaluated for dissolution and drug release properties using hydrochlorothiazide as a model drug. The effect of storage of GRF inside hard gelatin capsules on rate of swelling of the capsule shell and release of GRF was also studied. Storage for up to 12 months had no effect on capsule shell swelling and release of GRF. Gastric residence time, pharmacokinetics and bioavailability of hydrochlorothiazide, a drug that has an absorption window limited to the upper small intestine, from two different sizes of gastric retention formulations (GRF) were evaluated in 12 healthy volunteers in both fed and fasted states, and compared to immediate release tablets. Extent of bioavailability of drug from the larger formulation in this study was comparable to IR tablets in both fed and fasted states. Deconvolved input functions data suggest that the GRF stayed in the stomach providing sustained drug input for 12-28 hours. Initial blood pressure lowering and side effects of hydrochlorothiazide from a gastric retention formulation were evaluated and compared to immediate release tablets in 10 subjects with stage I hypertension. Gastric retention formulations produced an average reduction in systolic blood pressure 3 mm Hg lower than IR tablets regardless of sequence of administration. GRF also produced less blood pressure fluctuation in most subjects than IR tablets. Most subjects reported fewer and less severe side effects with GRF than IR tablets. / Graduation date: 2004