Date of Award
Master of Science (MS)
Dr. Thomas Needham
Levothyroxine Sodium is one of the most critical drugs for a significant segment of the population. The development of HPLC method of analysis for levothyroxine sodium revealed that there were significant stability problems associated with this drug. On August 14, 1997, FDA announced that there was evidence which shows significant stability and potency problems associated with orally administered levothyroxine sodium products. This lack of stability and potency has a potential to cause serious health consequence to the public. The literature, on determining the stable formulation of levothyroxine sodium is very little. Much of the published work on levothyroxine sodium describes the innumerable bioavailability and potency problems with this drug. However, little in the literature explored the stability of levothyroxine sodium in presence of various excipients. The portion of work in this thesis represents a series of investigations we have performed to evaluate the stability of levothyroxine sodium in presence of some of the most commonly used excipients at different temperatures and humidities. These studies indicated that levothyroxine sodium is unstable in presence of carbohydrates such as dextrose, lactose and starch. These excipients have an aldehyde group, which may be reacting with the free amino group of levothyroxine sodium leading to a Schiff-base reaction along with oxidation reaction.
In further series of investigations, the kinetics of degradation reactions were evaluated. First order and bi-phasic first order models were evaluated for our studies. Nonlinear regression was performed using Sigma Plot and the results suggest a biphasic-first order degradation pathway in most of the cases. The shelf life for levothyroxine sodium was determined using the k-values obtained from the best fit models. The lower t9o values indicated that levothyroxine sodium is highly unstable in presence of moisture and higher temperatures and so the tablets should be formulated and stored at or below room temperature with 0% humidity.
Amin, Niraj S., "Evaluation of Effect of Excipients, Temperature and Humidity on the Stability of Levothyroxine Sodium" (2000). Open Access Master's Theses. Paper 1152.