Influence of Formulation and Processing Factors on Stability of Levothyroxine Sodium Pentahydrate
Influence of Formulation and Processing Factors on Stability of Levothyroxine Sodium Pentahydrate
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DOI：
10.1208/s12249-010-9434-8
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发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Khan, Mansoor A.
中科院分区：
文献类型：
--
作者：
Collier, Jarrod W.;Shah, Rakhi B.;Khan, Mansoor A.
制剂在保质期内的稳定性对于获得优质产品至关重要。辅料、生产工艺、储存条件和包装的选择可减轻或增强活性药物成分（API）的降解，从而影响效价和/或稳定性。考察了加工和处方因素对左旋甲状腺素（API）稳定性的影响。将API在长期（25 A ℃/60%RH）、加速（40 A ℃/75%RH）和低湿度（25 A ℃/0%RH和40 A ℃/0%RH）条件下储存28天。通过将其干燥（室温，N-2）并置于25 A ° C/0%RH和40 A ° C/0%RH下来评价水分损失的影响。将API与各种赋形剂（基于市售片剂的包装说明书）以1：1、1：10或1：100的比例在60 A ℃和5%水分下孵育。使用常用的赋形剂比例。收集API和辅料的平衡吸附数据。两种剂型的API在所有条件下均在研究期间保持固态稳定（效价在90%至110%之间）。辅料对稳定性的影响各不相同，交聚维酮、聚维酮和月桂基硫酸钠（SLS）导致API发生显著降解，其中发生脱碘和脱氨基作用。不同辅料的吸湿值不同。交聚维酮和聚维酮具有吸湿性，而SLS在高RH下显示潮解。温度可能升高或湿度可能降低的瞬态配制程序不会对API稳定性产生重大影响。辅料会影响稳定性，如果可能，应避免使用这三种辅料或以最小量使用，以提供更稳定的片剂制剂，并在整个有效期内将效价损失降至最低。
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 (25A degrees C/60%RH), accelerated (40A degrees C/75%RH), and low-humidity (25A degrees C/0%RH and 40A degrees C/0%RH) conditions for 28 days. Effect of moisture loss was evaluated by drying it (room temperature, N-2) and placed at 25A degrees C/0%RH and 40A 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 60A 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.