STUDIES IN STABILIZATION OF LEVOTHYROXINE SODIUM TABLETS

Abstract

Levothyroxine is a salient medication that is used for the treatment of hypothyroidism. Levothyroxine have been recalled many times since its introduction to US market. For a quality product, stability over a shelf life is a critical parameter. Various parameter affects the stability of API like excipient used, process of manufacturing, various storage condition (temperature, moisture, humidity) as well as packaging of product, all these increases the degradation of levothyroxine and thus Potency. Experiments were performed to study and demonstrate the effect of formulation and various processing variable to study the stability of levothyroxine. At 60oC and 40oC/75% RH excipient and Levothyroxine are studies under ICH stability condition. Also tablet manufactured by wet granulation, dry granulation and direct compression are evaluated. For Six months, Levothyroxine found to be stable at 40oC/75% Relative Humidity both in open as well as closed containers. Tablets were manufactured by different excipients, SMCC, LHPC, Olive oil, Carrageenan, MCC. Tablets composed with SMCC (Silicified Microcrystalline Cellulose) failed to meet USP requirement at One and three months. 5% loss in potency after three and six months of accelerated stability study with pH modifier. Thus it is observed that use of different excipient in the manufacturing of levothyroxine affected the stability of Levothyroxine. Desiccant also help in maintaining the stability of Levothyroxine sodium tablet. Tablets manufactured by Wet granulation as well as direct compression, after 3 months of storage (ICH accelerated stability condition) there is not much difference in in stability/ Potency. Thus Manufacturing method/ process also affect the stability of levothyroxine sodium tablets. Thus it is observed that formulation as well as process affects the stability of levothyroxine tablets. KEY WORDS- Levothyroxine Sodium, Formulation, Stability, Excipients, Desiccant, Moisture, Humidity, shelf life, pH modifier, wet Granulation.