Characterization.
Particle-size distribution of the pellets was determined with a laser diffractometer (Mastersizer 2000, Malvern Instruments,
Malvern, UK) equipped with a dry-powder dispersing system (Scirocco 2000, Malvern Instruments, Malvern, UK) using a dispersion
pressure of 1 bar. Particle-size distributions were characterized by their volume median diameter d
0.5 (μm) and their pellet-size dispersion d
g. The pellet-size dispersion was calculated from d
0.5,
d
0.1, and d
0.9 according to the following equation:
where d
0.1 and d
0.9 values are the particle diameters corresponding to 10% and 90% of the cumulative distribution, respectively. The materials
were passed through a 2000-μm sieve before the measurement, and the pellet fraction over this size was re-entered in the results.
The pellets' mean size should be smaller than the diameter of the extruder die (i.e., 2 mm) because of the densification and
water evaporation that occurred during the spheronization and drying stages. The pellets' size dispersion was required to
be narrow as possible, expressed by a low (i.e., < 3) d
g value, to facilitate coating or capsule-filling operations.
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Pellet morphology was evaluated by microscopic observations (Stereo Microscope SMZ-168-TL and Moticam 2300 microscopes, Motic
Microscopes, Xiamen, China). The morphological analysis of pellets was performed by means of a particle-image analyzer (Morphologi
G2, Malvern Instruments). Analysis was carried out on roughly 300 pellets. Numerous parameters can be used to describe pellets'
shape. For the current study, pellet elongation (E) was calculated according to the following formula:
Because the pellets eventually are filled into capsules, they should present good flow characteristics and be as spherical
as possible. For a perfect disk, the value of the elongation factor equals 0. It is desirable to obtain pellets with the least
elongation possible.
The pellets' whole fraction was sieved on 1400–2000-μm sieves (Retsch, Haan, Germany) for 2 min, at a frequency of 60 Hz with
an amplitude of 1 mm. The 1400–2000-μm fraction of pellets was considered the usable fraction. The authors used this fraction
for pellets characterizations to eliminate the effect of size on the pellets' mechanical properties. The usable yield had
to be as high as possible.
Friability F(%) was measured on approximately 20 g of pellets from the usable yield fraction, to which were added 40 g of 6-mm glass beads.
After 30 min of blending in a 200-mL flask in a shaker–mixer (Turbula, GlenMills, Clifton, NJ) at 42 rpm, the mass retained
on a 1400-μm sieve was weighed, and the friability F(%) was calculated according to the following equation:
where Mi is the mass of granules before the test (i.e., 20 g) and Mf is the mass of granules retained by the sieve after the test. The test was performed in triplicate. The friability test showed
the pellet surface's resistance to abrasion, which should be as high as possible to avoid abrasion during further processing.
The resistance to crushing R(N) was tested on 20 pellets of the usable yield fraction with a durometer (Computest, Kraemer Elektronik, Darmstadt, Germany).
The diametral crushing force measured indicates the mechanical robustness of the pellets. It should be as high as possible
to avoid pellet breakage during further processing.
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