Influence of formulation and processing factors on stability of levothyroxine sodium pentahydrate.
Stability of formulations over shelf-life is critical for having a quality product. Choice of excipients, manufacturing process, storage conditions, and packaging can either mitigate or enhance the degradation of the active pharmaceutical ingredient (API), affecting potency and/or stability. The purpose was to investigate the influence of processing and formulation factors on stability of levothyroxine (API). The API was stored at long-term (25 degrees C/60%RH), accelerated (40 degrees C/75%RH), and low-humidity (25 degrees C/0%RH and 40 degrees C/0%RH) conditions for 28 days. Effect of moisture loss was evaluated by drying it (room temperature, N(2)) and placed at 25 degrees C/0%RH and 40 degrees C/0%RH. The API was incubated with various excipients (based on package insert of marketed tablets) in either 1:1, 1:10, or 1:100 ratios with 5% moisture at 60 degrees C. Commonly used ratios for excipients were used. The equilibrium sorption data was collected on the API and excipients. The API was stable in solid state for the study duration under all conditions for both forms (potency between 90% and 110%). Excipients effect on stability varied and crospovidone, povidone, and sodium laurel sulfate (SLS) caused significant API degradation where deiodination and deamination occurred. Moisture sorption values were different across excipients. Crospovidone and povidone were hygroscopic whereas SLS showed deliquescence at high RH. The transient formulation procedures where temperature might go up or humidity might go down would not have major impact on the API stability. Excipients influence stability and if possible, those three should either be avoided or used in minimum quantity which could provide more stable tablet formulations with minimum potency loss throughout its shelf-life.
Collier
Jarrod W
JW
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Life Sciences Bldg 64, Silver Spring, Maryland 20993-0002, USA.
Shah
Rakhi B
RB
Gupta
Abhay
A
Sayeed
Vilayat
V
Habib
Muhammad J
MJ
Khan
Mansoor A
MA
D004339:Drug Compounding / Q000379:methods; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D013974:Thyroxine / Q000737:chemistry*
D005079:Excipients; D013974:Thyroxine
Int J Pharm. 2003 Oct 2;264(1-2):35-43
12972334
J Pharm Sci. 1999 Jul;88(7):696-704
10393567
J Pharm Sci. 1997 Nov;86(11):1256-63
9383736
Int J Pharm. 2009 Oct 20;381(1):56-61
19486933
Int J Pharm. 2008 Aug 6;360(1-2):77-82
18524511
Int J Pharm. 2002 Apr 26;237(1-2):35-46
11955802
Adv Drug Deliv Rev. 2001 May 16;48(1):91-114
11325478
Clin Chem. 1989 Jan;35(1):90-2
2910586
J Clin Pharm Ther. 1990 Oct;15(5):331-6
2289935
Pharm Res. 1990 Apr;7(4):379-83
2362911
Pharm Res. 1992 Jan;9(1):131-7
1589398
J Pharm Biomed Anal. 2001 Jul;25(5-6):697-711
11377052