Influence of Formulation and Processing Factors on Stability of Levothyroxine Sodium Pentahydrate |
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Authors: | Jarrod W Collier Rakhi B Shah Abhay Gupta Vilayat Sayeed Muhammad J Habib Mansoor A Khan |
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Institution: | (1) 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;(2) Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, Washington, District of Columbia, USA;(3) Division of Chemistry III, Office of Generic Drugs, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA; |
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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°C/60%RH), accelerated (40°C/75%RH), and low-humidity
(25°C/0%RH and 40°C/0%RH) conditions for 28 days. Effect of moisture loss was evaluated by drying it (room temperature, N2) and placed at 25°C/0%RH and 40°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°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. |
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