Differential scanning calorimetry (DSC).
Samples of the drug, β-CD, physical mixture, and the kneaded complex were taken in flat round-bottomed aluminum pans and
heated in a temperature range of 50–300 °C at a rate of 10 °C per minute with nitrogen purging (50 mL/min) using alumina as
the reference standard in a differential scanning calorimeter (model pyris-1, Perkin Elmer, LLC, Norwallk, CT).
Powder x-ray diffraction (PXRD).
The diffraction studies of the drug, β-CD, physical mixture, and the kneaded complex were performed in a powder x-ray diffractometer
with a vertical goniometer (model PW 1050/37, Philips, the Netherlands). PXRD patterns were recorded using monochromatic CuK
a radiation with nickel filter at a voltage of 40 kV and a current of 20 mA between 5 and 308 2θ values.
An eight-run 23 factorial design consisting of three factors at two levels was set up to produce porous rapidly dispersing tablets of nabumetone
(15). The levels of ammonium bicarbonate (X1) and crospovidone (X2) were the numerical factors analyzed, whereas the effect of complexation (X3) was investigated as the categorical factor. The responses evaluated were the disintegration time (Y1), wetting time (Y2), and dissolution efficiency at 45 min (Y3). The selected factors and their corresponding levels as per the design are listed in Table I.
Table I: Factors and their corresponding levels as per 23 factorial design*.
A total of eight batches of dispersible tablets containing the drug either in the free or the precomplexed form were produced
by a wet granulation procedure using varying amounts of ammonium bicarbonate and crospovidone (16). The raw materials were
passed through sieve #100 (150 μm) before dry mixing. The mixtures of ammonium bicarbonate, crospovidone, mannitol, sodium
saccharine, and drug or its complex were dry mixed for 15 min in a glass mortar and pestle to obtain a uniform blend. The
powder blend was granulated for 5 min using a solution of poly(vinylpyrrolidone) K-30 in ethanol (10% w/v) and passed through
sieve #22 (710 μm). The granules obtained were air dried and passed through the same sieve to break the lumps.
The dried granules passing through sieve #22 (710 μm) and retained on sieve #44 (355 μm) were lubricated with magnesium stearate
and talc in a plastic bag for 5 min. The lubricated granules were compressed to tablets on a rotary tablet press (model Rimek
RSB-4 mini press, Karnavati Engineering, Ahmedabad, India) using 13-mm round, flat-faced bevelled-edge tablet B tooling. Each tablet weighing 650 mg contained 50
mg of the drug in the free or in the precomplexed form. The compressed tablets were dried in a vacuum oven (Lab model, Servewell Instruments, Bangalore, India) at 60 °C to a constant weight. The composition of the different batches of tablets produced as per the
23 factorial design is shown in Table II.
Table II: Composition of model formulations of nabumetone dispersible tablets prepared as per 23 factorial design.
Disintegration time was recorded following the Indian Pharmacopeia procedure in a USP XXIII disintegration tester (model ED-2L,
Electrolab Ltd (I) Ltd., Mumbai) (17). One tablet was placed in each tube of the apparatus using distilled water maintained at 37 ± 0.5
°C as a disintegrating medium. A conventional method was used to measure the wetting time and capillarity of the orodispersible
tablets (18). Wetting time was recorded at 25 °C in triplicate by placing a tablet in a 6.5-cm Petri dish, which contained
10 mL of water.