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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).
Figure 3: Powder x-ray diffraction patterns of (a) nabumetone, (b) b-cyclodextrin, (c) physical mixture, and (d) kneaded complex.
All figures are courtesy of the authors.
Powder x-ray diffraction. There were 11 peaks in the PXRD spectra of nabumetone and 24 peaks in the diffractogram of β-CD when the samples were scanned
between 0 and 30 2θ values (Figure 3). It has been reported that the total number of peaks in the kneaded product is the sum
of the number of individual peaks provided there is no interaction (24). Accordingly, 35 peaks were expected to appear in
the kneaded complex; however, the number of peaks that could be identified in the PXRD pattern of the complex was reduced
to 23. Moreover, the maximum intensities of the peaks recorded in the PXRD pattern of the drug, β-CD, and the complex were
11,000, 4200, and 1600 counts, respectively. This reduction in the number and intensities of the peak in the diffractogram
of the complex clearly demonstrated the decrease in drug crystallinity upon complexation.
The results from the FTIR, DSC, and PXRD studies collectively indicate considerable interaction between the drug and β-CD
that led to the reduction in the drug crystallinity. This decrease was responsible for the increased solubility of the kneaded
complex when compared with the pure drug.
Table III:Physical properties of model formulations of nabumetone dispersible tablets prepared as per 23 factorial design.
All figures are courtesy of the authors.
Several formulation variables influence the disintegration and dissolution of the tablets. A 23 factorial design was used to quantify the influence of different formulation variables on tablet properties of fast-dispersing
tablets of nabumetone prepared by the conventional wet granulation procedure. Ammonium bicarbonate was used as a subliming
agent, whereas crospovidone was used as a super disintegrant. Mannitol was incorporated as a filler to improve the palatability
of the tablets, whereas saccharine sodium was used as a sweetener. The effects of complexation in addition to the levels of
subliming agent and disinte grant on the tablet wetting, disintegration, and dissolution were systematically analyzed using
ANOVA and the F test.
Table IV: Response parameters of dispersible tablets of nabumetone prepared as per 23 factorial design. All figures are courtesy
of the authors.
The Indian Pharmacopeia has stated a maximum disintegration time of 3 min for dispersible tablets (19). With the aim to develop
a rapidly dispersible tablet formulation that would comply with the official monograph, a set of preliminary trials were undertaken
to establish the range of the each formulation variable. Based on the trials undertaken, the lower and upper levels of the
ammonium bicarbonate were retained at 10% and 30% of the tablet weight, respectively. The levels of crospovidone were varied
between 5% and 15% of the tablet weight, respectively, during the run. Factors such as the amount of drug in the tablet, tablet
hardness, and tablet thickness that were found to influence the response parameters were maintained constant during the run.
Considering the poor aqueous solubility of the drug, tablets were produced with 50 mg of nabumetone to ensure a sink condition
during dissolution testing.
