The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets.
Levothyroxine tablets, 50 microg, have been marketed for many decades but have had numerous recalls due to degradation and failure to meet potency. These experiments were devised to study the effects of various excipients on the stability of levothyroxine sodium pentahydrate in aqueous slurries and in formulated tablets. The active alone was found to be stable in the solid state for 6 months at 40 degrees C/75% RH whether stored in open or closed containers, and was found to be non-hygroscopic under normal processing conditions (>30% RH). In aqueous slurries with an excipient, the stability of the active improved as the pH of the slurry was increased from pH 3 to 11. Tablets manufactured with lactose anhydrous, starch, or microcrystalline cellulose failed to meet USP assay requirements at 3 months at 40 degrees C/75% RH. Tablets manufactured with dibasic calcium phosphate or mannitol met USP assay requirements at 3, but not 6 months when stored at 40 degrees C/75% RH. Tablets manufactured with dibasic calcium phosphate and a basic pH modifier, such as sodium carbonate, sodium bicarbonate, or magnesium oxide, met the USP assay requirements at both 3 and 6 months. Thus, the use of basic pH modifiers is a potential technique for improving the stability of levothyroxine sodium pentahydrate tablets.
Patel
Himanshu
H
College of Pharmacy, University of Cincinnati, 3223 Eden Ave., Cincinnati, OH 45219, USA. Patelhh@ucmail.uc.edu
Stalcup
Apryll
A
Dansereau
Richard
R
Sakr
Adel
A
D000327:Adsorption; D002130:Calcium Phosphates / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004349:Drug Packaging; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007785:Lactose / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D013213:Starch / Q000737:chemistry; D013607:Tablets; D013974:Thyroxine / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D017155:Wettability
D002130:Calcium Phosphates; D005079:Excipients; D013607:Tablets; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D014867:Water; D008353:Mannitol; C485838:calcium phosphate, monobasic, anhydrous; D002482:Cellulose; D013213:Starch; C020243:calcium phosphate; D007785:Lactose; C485829:calcium phosphate, dibasic, anhydrous; C109691:microcrystalline cellulose; D013974:Thyroxine