Methods

Preparation of Covidien ODTs. Covidien (Mansfield, MA) ODT placebo granules consist of four components described in the "Materials" section. The granules were prepared by using a top-spray fluid-bed granulation process. The ODT placebo granules were mixed with 1.0% (w/w) sodium stearyl fumarate in a V-blender for 5 min. The lubricated placebo granules were then made into placebo tablets for disintegration comparison or used for preparing ODTs containing a high dose of acetaminophen (APAP). The APAP-containing tablets were prepared by the following steps:

• Blend ODT placebo granules with taste-masked APAP granules in a V-blender for 20 min
• Add 1.0% (w/w) sodium stearyl fumarate as the lubricant to the powder blend from the first step and then mix for additional 5 min in the blender
• Compress the powder blend from the previous step to making tablets using a 16-station Manesty Betapress. The precompression force was 1300 N, and the main compression forces were 7 kN and 13 kN, respectively, at 60 rpm in 0.4062 and 0.5625-in. dies with round, flat-faced punches with beveled edges. The resulting tablet weights were targeted at 400 mg and 900 mg, respectively. For 900-mg tablets, the amount of APAP is shown in Table II.

Hardness test. The tablet crushing load, which is the force (kilopond, kp) required to break a tablet into halves by compression in the diametrical direction, was measured with a hardness tester (Varian Hardness Tester, VK-200).

Evaluation of disintegration times

In vitro test using the USP disintegration method (5). The disintegration times of the Covidien 400 mg and 900 mg APAP-containing ODTs and representative commercial ODT products were determined according to the USP 29, test number 701 (5). The disintegration time was determined when the last tablet fully disintegrated and all particles passed through the screen.

Table I: Optimum volume of the blue dye solution for a given tablet size.

Limited in vivo disintegration test in the mouth. An in vivo test of 900-mg placebo ODTs was conducted on four volunteers (three volunteers for 400-mg placebo ODTs). Each volunteer received 10 900-mg placebo ODTs, or 10 400-mg placebo ODTs, respectively. A placebo ODT was placed on the tongue of a volunteer, and the time for disintegration was measured by using a stopwatch. The ages of volunteers were between 20 and 60 years old. The participants were allowed to move the ODT against the upper roof of the mouth with their tongues and to cause gentle movement on the tablet without chewing it or tumbling the tablet from side to side. Immediately after the tablet disintegrated completely into small particles, the stopwatch was stopped and the time recorded. Forty 900-mg tablets and 30 400-mg tablets were evaluated accordingly and the results were reported.