The Disintegration and Dissolution of Nabumetone Dispersible Tablets - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

The Disintegration and Dissolution of Nabumetone Dispersible Tablets
Nabumetone was complexed with β-cyclodextrin, and a 23 factorial design was used to prepare dispersible tablets containing the drug or its complex.The authors analyzed the effects of complexation as well as the levels of ammonium bicarbonate and crospovidone on tablet wetting time (WT), disintegration time (DT), and percent dissolution efficiency at 60 min (%DE60).


Pharmaceutical Technology



Table V: Summary of ANOVA for the response parameters of the model formulations of dispersible tablets prepared as per 23 factorial design. All figures are courtesy of the authors.
The physical properties and response parameters of the different batches of model formulations are listed in Table III and Table IV, respectively. The disintegration time, percentage friability, weight, and content uniformity complied with official specifications.


Figure 4: 3-D plots showing the effect of formulation variables on disintegration time of tablets containing (a) nabumetone, and (b) nabumetone b-cyclodextrin complex. All figures are courtesy of the authors.
Disintegration time. The results of the analysis of variance along with the mathematical models generated are summarized in Table V. The DT of various model formulations ranged from 35 0.83 to 120 0.63 and depended on the bicarbonate and crospovidone levels. The linear model generated for DT was significant with an F value of 537 (p, 0.0001) and an R2 value of 0.999. The negative influence of the levels of ammonium bicarbonate and crospovidone on DT was clearly evident in the three-dimensional plots (see Figure 4).

DT decreased from 112.33 3.44 s to 72.66 2.78 s and from 91.33 3.16 s to 35 2.54 s at lower and higher levels of crospovidone, respectively, as the levels of bicarbonate increased in tablets containing the drug (see Figure 4a). This decrease in DT occurs because higher levels of subliming agent render the tablet more porous, which permits the water to contact with the disintegrant quickly, thereby causing rapid tablet disintegration. Reduction in DT with increase in the amounts of subliming agent has been reported previously when camphor was used as a subliming agent (25).

The plot illustrates that DT decreased from 112.33 3.44 s to 91.33 3.16 s and from 72.66 2.78 s to 35 2.54 s at lower and higher levels of bicarbonate, respectively, as the crospovidone increased. The three-dimensional plot revealed that the effects of bicarbonate and crospovidone on DT were more pronounced at higher levels. This result could be attributed to quick water uptake and rapid swelling of the super disintegrant at higher levels. A reduction in the DT of orodispersible tablets with an increase in the levels of crospovidone has been cited in the literature (26). The corresponding contour plots depict a nonlinear relationship between the two variables on DT and suggests that the DT can be minimized using high levels of subliming agent and disintegrant.

DT decreased from 121.66 4.52 to 81.33 3.78 s and from 99.66 4.12 s to 41.33 2.14 s at lower and higher levels of crospovidone, respectively, as the levels of bicarbonate increased in tablets containing the complex (see Figure 4 b). The plot also shows that DT decreased from 121.66 4.52 s to 99.66 4.12 s and from 81.33 3.78 s to 41.33 2.14 s at lower and higher levels of bicarbonate, respectively, as the levels of crospovidone increased. In addition to the main effects, the interaction effect X1X2 had a negative influence on DT.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

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

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
31%
Breakthrough designations
8%
Protecting the supply chain
42%
Expedited reviews of drug submissions
8%
More stakeholder involvement
12%
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology,
Click here