Table IV: Disintegration times of Covidien APAP-containing ODTs.
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Table IV shows both the wetting time as a simulated disintegration time and the disintegration time from the USP test of APAP-ODT (900-mg ODT containing 562.5mg Schwarz Pharma taste-masked APAP, or 450-mg APAP, and Covidien ODT placebo
granules). Although the tablet containing acetaminophen is bigger than 500 mg, both the in vitro disintegration times from the SWT method and the USP disintegration method were less than 30 s.
Table V: Disintegration times of selected ODT products.
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Table V shows the comparison between the wetting time using the SWT method and the disintegration time using the standard
USP method for six commercial ODT products. The USP disintegration times were consistently shorter than the wetting times for all ODTs in this study, regardless of tablet size.
For example, the disintegration time of 800 mg Zicam tablets using the SWT method was greater than 3 min, which is much closer
to in vivo test results, but the USP disintegration time of a Zicam tablet was as fast as 45 s. Similarly the 1000-mg PARCOPA tablet product showed the same trend
(147 versus 51 s). The wetting time of 1400-mg Excedrin QuickTabs using the SWT method and the disintegration time obtained
from the USP disintegration method were less than 30 s. The data in Table V also suggest that the magnitude of the values obtained in the
SWT test seem more differentiating than the magnitude of the values obtained from the USP test.
Overall, the results showed there was a strong correlation between the limited in vivo disintegration time and the in vitro wetting time using the proposed alternative method (SWT) for 400-mg and 900-mg Covidien placebo ODT tablets. The disintegration
times obtained from the SWT method are more closely mimicking the physiological conditions in the mouth. Advantages of the
SWT method include minimal requirement of equipment (Corning 12-well polystyrene plates, Whatman glass fiber paper disks,
1–10 mL auto pipettor, stopwatch, and a water-soluble blue dye solution). This test can serve as a simple, consistent, and
reproducible screening tool for evaluating disintegration time of ODTs to better estimate the disintegration time in the mouth.
As shown in Table III, the standard USP test did not sufficiently differentiate the disintegration time of a smaller size tablet from the results of a larger size
tablet. But the SWT method discriminated the disintegration times of two tablet sizes and closely agreed with their respective
disintegration times in the mouth in the limited in vivo test. ConclusionsThe proposed simple in vitro simulated wetting test (SWT), which embraces the physiological conditions of the mouth, for ODTs in this study showed a strong
correlation with the limited in vivo disintegration test in the mouth. The USP disintegration method for ODTs does not closely estimate the disintegration time of ODTs in this study in the oral cavity,
and it does not provide a realistic testing condition for evaluating an ODT. The results for commercial ODTs and Covidien
APAP containing ODTs using the proposed method indicated that the SWT can better differentiate the disintegration times of
the tested samples. We propose that the SWT method as described in this study should be considered as a standard USP test method for evaluating the disintegration time of ODTs in the future providing that the in vitro data are further validated with additional available in vivo disintegration times of the commercial ODT products to establish a strong IVIVC. Jae Han Park, PhD,* is a senior research associate. Kevin M. Holman, Glenn A. Bish, and Donald G. Krieger are formulation scientists. Daniel S. Ramlose is a senior research chemist. Cliff J. Herman, PhD, is a senior director. Stephen H. Wu, PhD, is a technical fellow, all at Pharmaceutical R&D of Mallinckrodt Pharmaceutical, Covidien, 385 Marshall Ave., Webster Groves,
MO 63119, tel. 314.654.2762, Jaehan.Park@Covidien.com
. *To whom all correspondence should be addressed. Submitted: Feb. 29, 2008. Accepted: April 2, 2008.
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