PREPARATION OF SUSTAINED-RELEASE GRANULES OF BUMETANIDE

Sustained release granules of bumetanide (BN) were prepared to obtain mild and sustained diuresis. BN was dispersed in combined matrixes of ethylcellulose (EC) with hydroxypropylmethylcellulose phthalate (HPMCP ), povidone (PVP) or cyclodextrins (CDs). Release of BN from these pre parations was evaluated by the JP XIII dissolution test in JP disinteg ration media No. 1 (pH 1.2) and No. 2 (pH 6.8) at 37 degrees C, The in teraction of BN with CDs in buffer solutions with different pHs was al so investigated, and BN from the preparation with the component of BN: gamma-CD:EC=1:4:2 (weight ratio) showed the most favorable sustained r elease pattern. The apparent stability constant of the gamma-CD system on the BN solubility was greater than those of the alpha- or beta-CD systems. Crystalline BN was not observed in this system in studies usi ng powder X-ray diffraction spectra and a differential scanning calori meter.