The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets

被引:38
作者
Patel, H
Stalcup, A
Dansereau, R
Sakr, A
机构
[1] Univ Cincinnati, Coll Pharm, Cincinnati, OH 45219 USA
[2] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA
关键词
levothyroxine sodium; tablets; excipient; stability; slurries; pH modifiers;
D O I
10.1016/S0378-5173(03)00387-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Levothyroxine tablets, 50 jig, 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 40degreesC/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 40degreesC/75% RH. Tablets manufactured with dibasic calcium phosphate or mannitol met USP assay requirements at 3, but not 6 months when stored at 40degreesC/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. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:35 / 43
页数:9
相关论文
共 15 条
[1]   Identification of the thermal degradation products of L-triiodothyronine sodium (liothyronine sodium) by reversed-phase high-performance liquid chromatography with photodiode-array UV and mass spectrometric detection [J].
Andre, M ;
Domanig, R ;
Riemer, E ;
Moser, H ;
Groeppelin, A .
JOURNAL OF CHROMATOGRAPHY A, 1996, 725 (02) :287-294
[2]   Effect of different acids on solid-state stability of an ester prodrug of a IIb/IIIa glycoprotein receptor antagonist [J].
Badawy, SIF ;
Williams, RC ;
Gilbert, DL .
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, 1999, 4 (03) :325-331
[3]   KINETICS OF DEGRADATION OF LEVOTHYROXINE IN AQUEOUS-SOLUTION AND IN SOLID-STATE [J].
CHONG, MW .
PHARMACEUTICAL RESEARCH, 1992, 9 (01) :131-137
[4]  
*FDA GUID IND, 1998, DRUG STAB TEST DRUG
[5]  
*FDA GUID IND, 2001, LEV SOD PROD ENF AUG
[6]   HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR SODIUM LEVOTHYROXINE IN TABLET FORMULATIONS - CONTENT UNIFORMITY APPLICATIONS [J].
GARNICK, RL ;
BURT, GF ;
LONG, DA ;
BASTIAN, JW ;
ALDRED, JP .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1984, 73 (01) :75-77
[7]  
GOODMAN L, 2001, PHARMACOLOGICAL BASI
[8]  
Gupta VD, 1990, J CLIN PHARM THER, V15, P331
[9]  
ICH Steering Committee, 2000, ICH HARM TRIP GUID
[10]   Impact of triethylamine as a mobile phase additive on the resolution of racemic amino acids on an (+)-18-crown-6-tetracarboxylic acid-derived chiral stationary phase [J].
Jin, JS ;
Stalcup, AM ;
Hyun, MH .
JOURNAL OF CHROMATOGRAPHY A, 2001, 933 (1-2) :83-90