*3.2. Dissolution*

In accordance with the United States Pharmacopeia (USP), the tablets are considered to be dissolved when 75% of the stated dosage has been released [17,18]. The USP method is used as a quality control method, which is normally deployed to identify variations during manufacturing or storage stability, and does not mimic the different physiological conditions of the gastrointestinal tract. The USP-stated method uses alkaline borate buffer (pH 10) and 0.01 N hydrochloric acid containing 0.2% sodium lauryl sulfate for T3 and T4, respectively, with no proposed method for dual-component tablets [20]. Therefore, to ensure consistency and allow a direct comparison between single- and dual-component tablets, biorelevant dissolutions were performed using simulated gastric and intestinal fluids. The results from the dissolution testing using the simulated gastric and intestinal fluids of the tablets for the single- and dual-component thyroid hormones are shown in Figure 2. It is noted that the dissolution for T3 and T4 occurs within approximately 45 min (i.e., 75% dissolution), which is in agreemen<sup>t</sup> with the USP method [17,18]. From Figure 2 it can also be seen that total release of T3 and T4 from the tablet formulations was obtained within 120 min.

**Figure 2.** Dissolution testing profile for T3 and T4 from single- and dual-supplement thyroid hormone supplements.

The kinetics of dissolution have been investigated using a first-order rate constant (Figure 3). It was observed that a two-stage dissolution process occurs with crossing points determined by extrapolation of the line of best fit. The initial rate constant corresponds to tablet coating dissolution while the second rate constant is indicative of tablet breakdown. The rate constants (k) were calculated to be between 5.3–6.1 h−<sup>1</sup> and 0.4–0.8 h−<sup>1</sup> for coating removal and tablet solubilization, respectively. The rate constant was calculated based on the change in cumulative % drug remaining over time ((y2 − y1)/(x2 − x1)) with y calculated using the equation of the line.

**Figure 3.** Kinetics of dissolution for T3 and T4 from single- and dual-supplement thyroid hormone supplements.
