000			03625nam a2200313 i 4500
999			_c12906 _d12906
005			20210307151614.0
008			210307s2002 -usa|||| m||| 00| 0 eng d
040			_aEG-NcFUE _erda
082	0	0	_221 _a615.1 _bH.E.A
100	1	0	_aHamed, ehab ahmed mamdouh _eauthor
245	1	0	_aApplication and evaluation of extended release technology to loop diuretics / _cEhab Ahmed Mamdouh Hamed .
264	1		_aCincinnati, Ohio : _bUniversity of Cincinnati, _c2002 .
300			_a208 pages : _billustrations ; _c23 cm.
336			_2rdacontent _atext
337			_2rdamedia _aunmediated
338			_2rdacarrier _avolume
500			_aIncludes abstract
502			_aThesis (Ph.D.)--University of Cincinnati, 2002
504			_aIncludes bibliographical references
520			_aLoop diuretics offer great advantages in treating edematous states associated with congestive heart failure, liver cirrhosis and kidney failure owing to their intense diuretic effect. Evidences suggested the diuretic effect can be exaggerated by careful control of the rate at which loop diuretics are made available to the urinary tubules. If optimally designed, peroral extended release formulation can provide better utilization of the same total dose of loop diuretic, an effect of utmost importance in edematous patients with high resistance to loop diuretics. Bumetanide multiparticulate immediate and extended release formulations were developed and tested in rabbits. A novel multiple response optimization technique based on superimposing contour diagrams was developed and successfully used to optimize bumetanide release. Instability in drug release from multiparticulate formulations after storage warrants in depth investigation of different formulation and processing factors controlling drug release. Curing time, temperature, plasticizer level, coating polymer lipophilicity, and the use of hydrophilic seal coat were explored in this study. The findings proved instability in bumetanide release is attributed to drug migration into the film coat during storage. Careful selection of plasticizer level and curing conditions together with the use of hydrophilic seal coat prevented drug migration and stabilized drug release after storage. When compared to immediate release formulation in rabbits, equivalent amounts of bumetanide were excreted from both formulations yet at different rates. The slow delivery of bumetanide from the extended release formulation improved its diuretic and natriuretic efficiencies within the first day after dosing. The activation of compensatory mechanisms is thought to diminish the response to extended release bumetanide formulation within the second day. While providing comparable diuretic and saliuretic effects to that of immediate release formulation, extended release bumetanide formulation can offer the advantage of avoiding the initial, unpleasant and intense diuretic effect experienced with immediate release formulations
650			_aPharmaceutical Sciences
700	1	0	_acacini,william _esupervisor.
700	1	0	_aGerson, Myron _esupervisor.
700	1	0	_aDesai , pankaj _esupervisor.
700	1	0	_aMillard , Ronlad _esupervisor.
700	1	0	_aSakr, Adel Mohamed, _933831 _esupervisor.
942			_2ddc _cTHESIS