The objective of the research proposal is to study the formulation and processing variables that influence the in vitro and in vivo availability of Triamterene (TRM)/Hydrochlorothiazide (HCT) combination oral solid dosage forms. TRM/HCT tablets and capsules are indicated for the treatment of serious diseases such as edema of congestive heart failure, hepatic cirrhosis, certain renal dysfunctions and hypertension. Serious problems could occur should these products exhibit fluctuations in their bioavailability. A study of the affects of the formulation factors such as diluents, disintegrants, and lubricants, and the processing variables, such as mixing time and compression pressure, will be carried out. Various diluents (Avicel, Emcompress, lactose, Delaflo and their combinations), disintegrants (Ac-Di-Sol, Polyplasdone XL, and Explotab) and lubricants (magnesium stearate, stearic acid, talc, and sodium stearyl fumarate) will be systematically evaluated. The mixing time (using P-K blender) and the compression pressure (using an instrumented Manesty D3B tableting press) over the practical range of operation will be studied. The objective is to develop acceptable tablet formulation(s) and processing variables that produce tablets of optimum mechanical strength (Heberlein crushing strength and Roche friability) and in vitro availability (USP XXI dissolution test). These tablets will then be subjected to an accelerated storage program to identify optimally stable tablets for further in vitro and in vivo availability studies. The in vivo availability of two of the formulations, selected based on their pharmaceutical quality and in vitro availability, will be tested in beagle dogs in comparison with the commercial capsule and tablet. Blood levels and urinary excretion of TRM and HCT and/or their metabolites will be analyzed (HPLC). Na+, K+ and creatinine excretion will be determined. Computer analysis will be performed to determine the relevant bioavailability/bioequivalence parameters such as the extent of bioavailability and the rate of bioavailability. A correlation will be attempted between Na+, K+ and total urinary output, and AUC, C-max and t-max.