title: Influence of formulation and processing factors on stability of levothyroxine sodium pentahydrate.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jarrod W
authors.initials: JW
authors.lastname: Collier
authors.forename: Rakhi B
authors.initials: RB
authors.lastname: Shah
authors.forename: Abhay
authors.initials: A
authors.lastname: Gupta
authors.forename: Vilayat
authors.initials: V
authors.lastname: Sayeed
authors.forename: Muhammad J
authors.initials: MJ
authors.lastname: Habib
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D004339:Drug Compounding / Q000379:methods; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D013974:Thyroxine / Q000737:chemistry*
chemical_list: D005079:Excipients; D013974:Thyroxine
references.citation: Int J Pharm. 2003 Oct 2;264(1-2):35-43
references.pmid: 12972334
references.citation: J Pharm Sci. 1999 Jul;88(7):696-704
references.pmid: 10393567
references.citation: J Pharm Sci. 1997 Nov;86(11):1256-63
references.pmid: 9383736
references.citation: Int J Pharm. 2009 Oct 20;381(1):56-61
references.pmid: 19486933
references.citation: Int J Pharm. 2008 Aug 6;360(1-2):77-82
references.pmid: 18524511
references.citation: Int J Pharm. 2002 Apr 26;237(1-2):35-46
references.pmid: 11955802
references.citation: Adv Drug Deliv Rev. 2001 May 16;48(1):91-114
references.pmid: 11325478
references.citation: Clin Chem. 1989 Jan;35(1):90-2
references.pmid: 2910586
references.citation: J Clin Pharm Ther. 1990 Oct;15(5):331-6
references.pmid: 2289935
references.citation: Pharm Res. 1990 Apr;7(4):379-83
references.pmid: 2362911
references.citation: Pharm Res. 1992 Jan;9(1):131-7
references.pmid: 1589398
references.citation: J Pharm Biomed Anal. 2001 Jul;25(5-6):697-711
references.pmid: 11377052