About 13% of Americans suffer from hypothyroidism .
Levothyroxine (T4), a Narrow Therapeutic Index (NTI) drug is used for
treating hypothyroidism. Levothyroxine is administered orally with a
bioavailability 40-80% when fasting. However, the absorption of
levothyroxine is decreased when it is taken with food or certain drugs.
Patients therefore must take levothyroxine 0.5-1 hour before ingestion of
food or other medication. To improve patient compliance, efficacy and ease
of use, other forms of drug delivery systems i.e. transdermal patch should
be fully evaluated. We aim to investigate the factors influencing
transdermal absorption of levothyroxine (either as free acid or various
salts) with a long-term objective of developing an alternative dosage form
for this medication. A transdermal patch for levothyroxine is expected to
improve the ease-of-use while avoiding the food and drug interactions. The
Specific Aims are:
Aim 1: To establish a sensitive Liquid
Chromatography tandem Mass Spectrometry (LC MS/MS) method for detection of
T4 and related compound in various matrices (in water, formulations, human
and animal plasma) for quantification and stability indications.
Aim 2: To test and compare transdermal diffusion
rates of sodium salt and the acid form of T4 on cell cultures and the skin
of hairless guinea pigs.
Aim 3: To monitor and test the stability of T4 in
the presence of stabilizers, co-solubilizer, permeation enhancers, etc.
for the use of transdermal delivery.
