Table III: Particle-size distribution and physical characteristics of PanExcea MHC300G (three sample lots).
Physical characterization of PanExcea MHC300G performance excipient. Composition and particle morphology. The SEM micrographs (see Figure 4) of particles obtained using several manufacturing processes and compositions (see Table
I) show the particle morphology of all materials as being different. The MHC300G containing 89% MCC, 2% HPMC, and 9% CPVD
has homogeneous spherical to quasi-spherical particles with a rough surface and some open pores (see Figure 4A). The increase
in concentration of HPMC to 5% (EMB001) triggered a significant increase in the open pores (see Figure 4B). The difference
in porosity is also reflected in changes in aerated bulk density and tapped density. The higher densities of MHC300G indicate
denser particles as compared with EMB001 (see Table II). The composition of MHC300G was finalized to provide optimal particle
shape, size, and porosity needed for direct compressible materials (see Figure 3). The SEM micrographs of the high-shear granulated
material (EMB002) having similar composition to that of MHC300G show agglomerated particles (see Figure 4C), while the MCC
shows typical needle-shaped particles (see Figure 4D) (19).
Figure 5: Flowability index for EMB003 (powder blend), EMB002 (HSWG), MHC300G, and commercial grades of microcrystalline cellulose
(MCC) (Avicel PH 102, Emcocel 90). Higher index indicates better flowability (see Reference 21).
Particle-size distribution and flowability parameters. The average particle size and the particle-size distribution of a granular material is known to impact flowability, blending
ability, wetting, drying, mechanical properties, and stability (4). The flowability of pharmaceutical blends (i.e., API plus
excipients) is critical for effective use of direct compression. Poor flow can cause bridging, arching, surging, and enhanced
movement of particles in the die cavity. There are few simple acceptable tests to evaluate the flowability of a powder, the
Hausner ratio and measurement of total flowability index being just few of them (20, 21). The Hausner ratio is defined as
the ratio of tapped to aerated bulk density, where values < 1.25 indicate good flow properties. The total flowability index,
as described by Carr, is calculated based on a series of measurements of powder properties (e.g., angle of repose, aerated
and tapped bulk density, and particle-size uniformity) using a Hosokawa powder tester (21, 22). The values of the flowability
index range from 0 to 100, with 100 being the material with the best flow properties. A material with a total flowability
index of > 80 has very good flowability.
Table IV: Granules friability test* for the MHC300G using a V-blender. Comparison with a granular product of similar composition
obtained by high-shear wet granulation.
The particle-size distribution and the physical characteristics of MHC300G are summarized in Table III. A total flowability
index greater than 80, an angle of repose below 35°, and a Hausner ratio less than 1.25 indicate that MHC300G has very good
flowability. When compared with various grades of MCC, EMB001, EMB002, and EMB003, MHC300G provides superior performance in
terms of flowability (see Table II and Figure 5). For example, Avicel PH 102 has a Hausner ratio of ~ 1.33, a compressibility
index of ~ 25% and a total flowability index of 72, and MHC300G has a Hausner ratio of 1.21, a compressibility index of ~
17 % and a total flowability index of 87. These data suggest that the processing methodology used in MHC300G particle engineering
improved flowability attributes significantly.
Table V: Granules friability test for the MHC300G using high shear or mill.*
Particle strength. The particles used in a DC process should be strong and not produce fines during blending or mixing operations. The MHC300G
granules and a granular material of similar composition prepared by conventional HSWG (EMB002) were tested in a particle friability
experiment. Upon tumbling samples of excipients in a V-blender for two hours, the percentage of fines was unchanged for MHC300G,
but for EMB002 (see Table IV) they were doubled. The strength of the MHC300G particles was tested also in a high-shear process
in which the impeller was run at 950 rpm for 5 min, or by passing the MHC300G excipient through a mill at 3000 rpm and a mesh
size corresponding to US # 16 (1180 µm). All tests showed (see Table V) that the particles did not break during the process
and the percentage of fines did not increase. The granule-strength studies and the SEM micrographs indicated that the MHC300G
performance excipient consists of strong particles with robust bonding bridges between the granules' components, resulting
in a unique structural morphology.
Figure 6: Tensile strength versus compression force profile for tablets (10 mm diameter) prepared from MHC300G/0.25%Mg stearate
blend, and MCC/2%HPMC/9%CPVD/0.25%Mg stearate blend (MCC is microcrystalline cellulose, HPMC is hydroxypropyl methylcellulose,
and CPVD is crospovidone).
Table VI: Ibuprofen formulations used in tableting studies.
Tableting study of MHC300G. PanExcea MHC300G was designed to ensure its use in high-speed tableting machines. Its physical properties, functional characteristics
(i.e., flowability and compressibility) and particle strength indicate its suitability for DC processes in high-speed tableting
machines. A tableting study was undertaken to understand the compaction profile and the variation in tablet properties with
tableting parameters. The effect of turret-rotation speed on tablet quality (i.e., the strain rate) was studied as it is very
important for tableting process scale-up. Placebo tablets of MHC300G/Mg stearate (0.25%) and a powder blend of MCC/HPMC (2%)/CPVD
(9%)/Mg stearate (0.25%), respectively, were obtained using a 10-station rotary tableting machine configured with 10-mm round
standard concave TSM "B" tooling.