In vitro dissolution and in vivo bioavailability of commercial levothyroxine sodium tablets in the hypothyroid dog model.
The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).
Wood
R W
RW
Baxter Healthcare Corporation, Round Lake, IL 60073.
Martis
L
L
Gillum
A W
AW
Roseman
T J
TJ
Lin
L
L
Bernardo
P
P
D000818:Animals; D001682:Biological Availability; D004285:Dogs; D006207:Half-Life; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D012995:Solubility; D013607:Tablets; D013974:Thyroxine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D013607:Tablets; D013974:Thyroxine