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An Alternative to the USP Disintegration Test for Orally Disintegrating Tablets
The authors propose an alternative to the USP disintegration test method. The method embraces physiological conditions of the oral cavity, as a screening tool for developing ODT products.
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 .
Physical properties of the tested ODT products. Table II lists the physical properties of three Covidien ODT preparations and six ODT commercial products. In general, the
hardness values of all six commercial ODT products were between 1.8 and 7.9 kp for tablet weights in the range of 27–1400
mg. Therefore, most of the currently commercial products were packed in blister packs because of relatively low tablet hardness.
However, Covidien ODTs were mechanically stronger and suitable for a conventional HDPE bottle packaging with both tablet sizes
(400 mg and 900 mg). The ODT products in Table II are representative for understanding how the disintegration time of an ODT
is influenced by the respective tablet size.
ODT disintegration times. The disintegration times for both the 400-mg and 900-mg placebo ODTs were determined using three different methods: conventional
USP disintegration test method as recommended by the FDA, limited in vivo disintegration test in the mouth, and SWT method proposed in this study.
Table III: Disintegration times of Covidien placebo ODTs.
Table III shows that the average disintegration times of the ODTs according to the USP method were about 9 s for the 400-mg tablets and 12 s for the 900-mg tablets. The average disintegration times of 400-mg and
900-mg placebo ODT tablets using the SWT method were about 14 and 25 s, which are closer to the respective data of the limited
in vivo test. The average disintegration times of both the 400-mg and 900-mg placebo ODT tablets in the mouth were about 16 and 24
s, respectively. Thus the USP disintegration times showed a poorer correlation with the limited in vivo disintegration times, but the results from the SWT method showed a stronger correlation with the limited in vivo disintegration times. The SWT method further showed the larger differences in the disintegration times for two tablet sizes.
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.
