Materials and methods
CNZ was supplied by Rakshit DPL (Bombay, India). Lactose monohydrates and PEG 6000 were procured from S.D. Fine Chemicals
(Mumbai, India). All chemicals and solvents used in this study were of analytical reagent grade. Freshly distilled water was
used throughout the work.
Fluidized-bed melt granulation.
CNZ, PEG, and lactose monohydrate were granulated in a fluidized-bed dryer. The unit consisted of a conical container with
a fine-mesh nylon gauze air distributor, stainless-steel support gauze, and a filter bag at the top of the unit. In the granulation
experiments, various temperatures (56, 60, 64, and 68 °C) were used to melt the PEG. A temperature controller provided an
accuracy of ±1 °C. The mean air speed was maintained at predetermined levels (350, 450, 550, and 650 m3/h). The 200-g formulations were co-melted and fluidized for predetermined periods (5, 10, 15, and 20 min). Because the granulation
temperature exceeded the melting temperature of PEG, the granules were cooled and consolidated by fluidizing the granulate
under ambient air for 30 s at the end of each granulation run. This experimental procedure ensured rapid crystallization of
the PEG and is referred to as short isothermal crystallization time (ICT) (5).
Differential scanning calorimetry (DSC) analysis. DSC scans of powdered samples from all of the ingredients individually and of the melt granules were recorded using a DSC-
Shimadzu 60 instrument with TDA trend line software. All samples were weighed (8–10 mg) and heated at a scanning rate of 20
°C/min under dry airflow (100 mL/min) between 50 and 300 °C. Aluminum pans and lids were used for all samples.
Granule size and shape. A granule-size distribution study was performed with a vibrating sieve shaker (Kevin Engineering, Ahmedabad, India) (11).
Granules' size, shape, and surface were characterized with a scanning electron microscope (SEM, Philips XL30 ESEM TMP, FEI, Hillsboro, OR).
Friability. A friability test was carried out with 10-g granules placed in a Roche friabilator (Campbell Electronics Mumbai, India) for
5 min at 25 rpm (11).
Drug content. Granules were dissolved in methanol. The drug content was determined with a UV spectrophotometer at 254 nm (Shimazdu-1601
UV–vis spectrophotometer, Shimadzu, Kyoto, Japan).
Ungranulated materials. The presence of powder materials that were not granulated may be attributed to insufficient binder concentration or fluidization.
The materials were retained as ungranulated and weighted against total weight of materials.
Dissolution study. Dissolution studies of all samples were performed with USP XXIII apparatus type 2. Granules equivalent to 25 mg of CNZ were added to the dissolution medium (900 mL of distilled water
at 37 ± 0.5 °C), which was stirred with a rotating paddle at 50 rpm. At suitable time intervals, 10-mL samples were withdrawn,
filtered (0.22 μm), diluted, and analyzed at 254 nm with the UV spectrophotometer. An equal volume of fresh medium prewarmed
at the same temperature was replaced in the dissolution medium after each sampling to maintain its constant volume throughout
the test. Each test was performed in triplicate, and calculated mean values of cumulative drug release were used while plotting
the release curves (13).
Figure 2: Differential scanning calorimetry spectra of granules prepared with (a) melt granulation, (b) cinnarizine, (c) lactose
monohydrate, (d) poly(ethylene glycol) 6000. (FIGURE IS COURTESY OF THE AUTHORS)