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Dynamic avalanching accurately assesses flowability and quality
The amount of fine (d10 µm) particles in bulk antibiotics can be a source of problems during the production of finished dosage forms as they can be subjected to forces of agglomeration and/or cohesion, resulting in poor powder flow and non-uniform drug dispersion in a formulation blend.
Cefaclor is a β-lactam cephalosporin antibiotic that has a wide particle size distribution. Because of the nonporous nature
of the material, the specific surface area value accounts for a significant amount of fine particles possibly present in the
samples under analysis. In light of this, dynamic avalanching measurements were performed on Cefaclor samples characterized
by comparable particle size distribution curves, but different specific surface area values.
What is dynamic avalanching?
Table 1: Tested powder samples.
Dynamic avalanching is a technique for investigating powder flow properties under dynamic conditions and has, in the last
decade, received growing attention from the scientific community.1,2 Powder avalanching in a rotating drum enables the evaluation of dynamic powder flow characteristics on the basis of deterministic
chaos theory.3
Table 2: Fine particle content of the analysed samples.
In the last few years, the commercial availability of automated powder flowability analysers has contributed to the widening
acceptance of this analytical technique in the pharmaceutical industry.4,5 The first instrument launched on the market, AeroFlow (TSI Inc. Particle Instruments/Amherst, MA, USA), was based on a rotating
plexiglas drum that contained the powder to be tested. The powder movement was monitored by a light and photocell arrangement;
the photocell, located behind the drum, collected the light passing through the drum and recorded light variations resulting
from cyclic formation of avalanches. Kaye has reported the theoretical basis for this commercial device.3,6,7
Table 3: Specific surface area of the analysed samples.
Because of the limits intrinsic to its own arrangement, AeroFlow has been replaced by the more versatile Revolution powder
analyser (Mercury Scientific Inc., SC, USA), which features a more powerful detection system. In this instrument, a video
camera, with the assistance of a cold cathode back-light illumination, captures images of the whole powder contained in the
drum during the rotation process. With AeroFlow, however, information regarding the powder sample was limited to just a small
portion of it.
Table 4: Most conventional flowability descriptors measured after fluidization.
Cefaclor suitability for formulation purposes is assessed on the basis of both particle size distribution data and specific
surface area (SSA) values obtained from air permeability measurements. These measurements are essential to discriminate between
'suitable' and 'unsuitable' samples because, as a nonporous material, Cefaclor's SSA values are related to the content of
particles with an average diameter in the 0.2–50.0 µm range.8 If these fine particles are present in a significant quantity, then they can negatively affect successive formulation operations.
Figure 1: Overlay of power attractions for sample 1 and sample 4.
In our study, Revolution was used to test the flowability of Cefaclor; the analyses were performed on the samples with similar
particle size distribution, but with slightly different fine (≤ 10 µm) particle contents. The aim of the dynamic avalanching
measurements was to see if differences among the analysed samples influenced their flowability characteristics and, if so,
which among the typical descriptors that can be derived from these measurements (e.g., avalanche time, avalanche power, surface
fractal, etc.) was more informative to reveal these differences.
Riccardo Bonfichi is Corporate Quality Control Director and Qualified Person at ACS Dobfar ApA (Italy).
riccardo.bonfichi@acdobfar.net
Tel: +39 33 4656 1731
Fax: +39 02 9069 3226
Articles by Riccardo Bonfichi
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