The Disintegration and Dissolution of Nabumetone Dispersible Tablets - Pharmaceutical Technology

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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).


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Figure 5: Three-dimensional plots showing the effect of formulation variables on wetting time of tablets containing (a) nabumetone and (b) nabumetone b-cyclodextrin complex. All figures are courtesy of the authors.
Wetting time. WT of different model formulations ranged from 21.33 1.78 s to 73.66 3.22 s and depended on the levels of bicarbonate and crospovidone. The predictor equation generated for WT was significant, with an F value of 887.48 (p < 0.0001) and an R2 value of 0.999. The three-dimensional plots demonstrate the negative influence of the bicarbonate and crospovidone levels on WT (see Figure 5).

WT decreased from 67.33 2.41 s to 43.00 2.10 s and from 54.66 2.15 s to 21.33 1.78 s at lower and higher levels of crospovidone, respectively, as the levels of bicarbonate increased in tablets containing the drug (see Figure 5a). This result can be attributed to the fact that high subliming agent levels left the tablet porous, which made the water easily accessible to the disintegrant and caused rapid tablet wetting.

The plots also show that WT decreased from 67.33 2.41 s to 54.66 2.15 s and from 43.00 2.10 s to 21.33 1.78 s at lower and higher levels of bicarbonate, respectively, as the crospovidone increased. The effects of bicarbonate and crospovidone on WT were more evident at higher levels than at lower levels as demonstrated by the three-dimensional plot. This result could be attributed to a rapid water uptake by the super disintegrant at higher levels.

WT decreased from 73.66 3.22 s to 48.33 2.32 s and from 60.66 3.41 to 25.00 1.52 s at lower and higher levels of crospovidone, respectively, as the levels of bicarbonate increased in tablets containing the complex (see Figure 5b). The plot also shows that WT reduced from 73.66 3.22 s to 60.66 3.41 s and from 48.33 2.32 s to 25.00 1.52 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 also had a negative influence on WT.


Figure 6: Plots showing the effect of formulation variables on dissolution efficiency of tablets containing (a) nabumetone and (b) nabumetone b-cyclodextrin complex. All figures are courtesy of the authors.
Dissolution efficiency. DE at the end of 45 min (%DE45) of the tablets containing the drug varied from 37.93 1.05 to 41.21 0.71, whereas tablets containing the complex exhibited %DE45 ranging between 61.20 1.84 and 66.50 1.52. The linear model generated for %DE45 was significant with an F value of 408.05 (p < 0.0001) and R2 value of 0.9885. Complexation was the lone factor that significantly influenced %DE45. The lack of any significant influence of the levels of ammonium bicarbonate and crospovidone on %DE45 of the tablets was clearly demonstrated in the three-dimensional plots shown in Figure 6. Complexation of the drug with β-CD, which improved drug solubility, was the major contributing factor responsible for the enhanced dissolution rate and the value of %DE.


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