The objective of this study was to develop a losartan potassium sustained-release and hydrochlorothiazide immediate-release formulation for the treatment of hypertension. This can be achieved by formulating microbeads on the basis of a regular 32-factorial design. The microbeads of Losartan Potassium were prepared by an ionotropic gelation technique using excipients such as gellan gum, calcium chloride, and chitosan. Compatibility studies of drugs and polymers were performed by FTIR spectroscopy and DSC. A variety of measurements were carried out on the microbeads, such as measurement and drug entrapment efficiency, bulk density, compressebility index, Hausner’s ratio, scanning electron microscopy, dissolution rate studies, and in vitro drug release. Sodium lauryl sulfate, sodium bicarbonate, croscarmellose, and sodium starch glycolate were used as excipients for hydrochlorothiazide immediate release granules. FTIR spectroscopy and DSC were used to conduct drug and polymer compatibility investigations for tablets made from hydrochlorothiazide quick-release granules. The tablets were then evaluated for bulk density, Carr’s Compressibility index, Hausner's ratio, disintegration test, and uniformity of drug content. FTIR spectroscopy and DSC studies revealed that there was no possible interaction between drugs and polymers. The in vitro release of Losartan Potassium is within the limit. The minimum disintegration time of Hydrochlorothiazide immediate release tablets was found in formulation (GF7), which was selected as an optimized formulation. Granules of hydrochlorothiazide were found to contain the medicine in formulation (GF7), which was chosen as the best formulation. Losartan