An Alternative to the USP Disintegration Test for Orally Disintegrating Tablets - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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.


Pharmaceutical Technology
Volume 32, Issue 8


Table IV: Disintegration times of Covidien APAP-containing ODTs.
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.
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.

Conclusions

The 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,
.

*To whom all correspondence should be addressed.

Submitted: Feb. 29, 2008. Accepted: April 2, 2008.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
27%
Oversee medical treatment of patients in the US.
12%
Provide treatment for patients globally.
8%
All of the above.
46%
No government involvement in patient treatment or drug development.
7%
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
Source: Pharmaceutical Technology,
Click here