FORMULATION AND ASSESSMENT COMBINATION OF SUSTAINED-RELEASE LOSARTAN POTASSIUM AND IMMEDIATE-RELEASE HYDROCHLOROTHIAZIDE

Bimal Debbarma* and Chandra Kishore Tyagi

ABSTRACT

The present study was aimed to develop bilayer tablets of Losartan potassium as Immediate Release layer and hydrochlorothiazide as Sustain Release layer to treat hypertension in type II diabetic patients. Hypertension is also one of the complications of type II Diabetes. The bilayer tablets were formulated to reduce the polytherapy to monotherapy, thus improving patient compliance. The tablets were formulated using hydrophilic polymers such as HPMC K4M and HPMC K100M in varying ratios to retard the drug release for a period of 10 hours. The immediate release layer of Losartan Potassium was formulated using Sodium Starch Glycolate (2% and 4%). The Drug-excipient interaction was investigated with FTIR spectroscopy. The study indicated that there was no interaction between the drugs and the excipients used in the formulations.The tablets were formulated by wet granulation technique because of the poor flowproperty of the drugs and blends. The formulated granules were evaluated for precompression studies which showed that the flow property was good. The formulated tablets were found to be within the limits with respect to uniformity of weight, hardness, thickness, diameter and friability. The disintegration time of Immediate Release tablets containing SSG 4% was found to be optimum. The drug content of the formulated Immediate Release tablets and Sustain Release tablets was found to be within the limits. The drug content of the bilayer tablets were estimated by simultaneous estimation method and it was found to be within the Pharmacopoeial limits. The in vitro dissolution study of the optimized bilayer tablets containing HPMC K4M and HPMC K100M in the 1:1 ratio retarded the release and met the IP specifications. The release kinetics of the optimized tablets showed that it follows first order release kinetics. The release of the drug from the matrix layer was depending on diffusion, swelling and erosion of the polymer. The stability studies indicated that the bilayer tablets were stable and do not show any significant changes in the physical characteristics, drug content and dissolution. The results obtained were found to be within the limits.

Keywords: Losartan potassium, Hydrochlorothiazide, Ethyl cellulose, Microcrystalline cellulose, Lactose, Starch, Sodium starch glycolate.