TY  - BOOK
AU  - Patel,Himanshu
AU  - Sakr,Adel Mohamed
TI  - The effect of formulation and processing variables on the stability of levothyroxine sodium tablets
U1  - 615.1 21
PY  - 2003///
CY  - Cincinnati, Ohio
PB  - University of Cincinnati
KW  - levothyroxine sodium
KW  - medicine
N1  - Includes abstract; Thesis (Ph.D.)--University of Cincinnati, 2003; Includes bibliographical references
N2  -  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
ER  -