Results and discussion

Optimization of the blue dye solution in the simulated wetting test. The average volume of saliva and the condition of the tongue surface play a key role in assessing the disintegration time of an ODT in the mouth. The rate of saliva secretion is 0.2–0.4 mL/min when resting and can increase to as much as 2 mL/min when stimulated. Therefore, the average rate of saliva secretion is about 0.5–0.7 mL/min (14), and the tongue surface is generally wet. These two factors were specifically considered in developing the new alternative disintegration test method (SWT) for ODTs. The optimum volume of the test medium (blue dye solution) must be adjusted within a range of 0.5–2.0 mL, mimicking the in vivo conditions in the mouth according to various tablet weights. Table I shows the recommended volume of the blue dye solution for various tablet sizes. The optimum volume of dye solution was established by correlating limited in vivo disintegration times of Covidien placebo ODTs and APAP-containing ODTs with the wetting times of the respective tablet sizes.

Table II: Physical properties of Covidien ODTs and commercial ODTs .

Table III: Disintegration times of Covidien placebo ODTs.

Furthermore, volunteers were asked to collect saliva in a 10-mL graduate cylinder for three minutes to see how the disintegration time was influenced by the production rate of saliva per minute. The disintegration time of the tablets in the mouth of a volunteer with more saliva produced in a minute was 2–4 s faster than the results from other volunteers.