A Comparison of Three Extrusion Systems - Pharmaceutical Technology

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A Comparison of Three Extrusion Systems
The authors conducted an experiment to determine the type of extrusion that provides the best productivity and pellet quality. This article contains online bonus material.

Pharmaceutical Technology
Volume 35, Issue 1

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.

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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