000			03859nam a22002657i 4500
999			_c12900 _d12900
005			20210308125659.0
008			210307s2003 -usa|||| m||| 00| 0 eng d
040			_aEG-NcFUE _erda
082	0	0	_221 _a615.1 _bP.H.E
100	1		_aPatel, Himanshu _eauthor.
245	1	4	_aThe effect of formulation and processing variables on the stability of levothyroxine sodium tablets / _cHimanshu Patel ؛committee chair adel sakr.
264		1	_aCincinnati, Ohio : _bUniversity of Cincinnati, _c2003.
300			_a144 pages : _billustrations ; _c30 cm.
336			_2rdacontent _atext
337			_2rdamedia _aunmediated
338			_2rdacarrier _avolume
500			_aIncludes abstract
502			_aThesis (Ph.D.)--University of Cincinnati, 2003
504			_aIncludes bibliographical references
520			_a Abstract: These series of experiments were devised to study the effects of various formulation and processing variables on the stability of levothyroxine. The studies were performed with levothyroxine drug substance (powder or solution), excipient slurries with levothyroxine at 50ʻC and tablet-incorporated levothyroxine under ICH accelerated stability conditions. Additionally, stability of tablets manufactured by wet granulation and / or direct compression at different compression pressures was evaluated under ICH accelerated stability conditions. It was found that the active, levothyroxine, was stable when stored for six months at 40ʻC/75% Relative Humidity (RH) in open or closed containers; also, it was non-hygroscopic under normal operating conditions (>30%RH). In diluent slurries when stored at 50ʻC for one month, levothyroxine was more stable at pH 11 than at pH 3. Levothyroxine tablets manufactured with dibasic calcium phosphate or mannitol and stored under accelerated stability conditions met USP assay requirements at three months, but not at six months. Tablets manufactured with lactose anhydrous, starch, and microcrystalline cellulose failed to meet USP requirements at three months. After six months at accelerated stability conditions, tablets manufactured with basic pH modifiers had less than 5% loss in potency, and thus, they met USP assay requirements. Therefore, it was concluded that excipients used in the manufacture of levothyroxine tablets affected levothyroxine stability. The use of desiccant for while storing levothyroxine tablets, didn't appear to affect their stability at ICH accelerated stability conditions. Furthermore, the use of basic pH modifiers is a technique for improving tablet- incorporated levothyroxine stability. After 3 months storage at ICH accelerated stability conditions the tablets manufactured by wet granulation or direct compression did not show significant difference in stability. Thus, the type of manufacturing method does not influence the stability of levothyroxine tablets, manufactured with / without sodium carbonate and using dibasic calcium phosphate as diluent. Interestingly, it was found that the initial assay value of levothyroxine tablets (compressed at 2000 and 6000 lbs) was lower than that of the uncompressed granules/powder. Thus tablet compression appears to affect the stability of levothyroxine. It was concluded that formulation and processing variables affect the stability of levothyroxine tablets
650	0	0	_alevothyroxine sodium _xmedicine
700	1		_aSakr, Adel Mohamed, _esupervisor. _933831
942			_2ddc _cTHESIS