Pharmaceutical Manufacturing Handbook: Production and

inders, disintegrants, glidants, lubricants, and fl avors) and APIs. In order to successfully
manufacture acceptable pharmaceutical products, these materials must
be adequately mixed and/or granulated to ensure that the resultant agglomerates
possess the required fl uidity and compressibility and, in addition, avoid demixing
during postgranulation processes. Moreover, the fi nal characteristics of tablets or
capsules such as drug dissolution rate, disintegration time, porosity, friability and
hardness are signifi cantly infl uenced by the properties of the powder blends used
during their manufacture.
During product manufacture large volumes of powder blends are fed through
production equipment/processes, and it is essential to be able to accurately
determine, defi ne, and control powder properties to ensure reproducible manufacture
and product performance. Therefore the characterization of the physicochemical
properties of powder blends is extremely important. It is well accepted
that there are inherent diffi culties in characterizing the entire mass of a bulk
powder blend or process stream, so it is essential to remove and analyze discrete
samples.
Sampling is a useful technique that allows an appropriate aliquot to be withdrawn
from the bulk so as to collect a manageable amount of powder which is representative
of the batch [3] , in other words, every particle should have an equal chance of
being selected [4] . However, there are many circumstances that may result in the
selection of nonrepresentative samples and hence the defi nition of powder characteristics
that are not a true estimation of the entire bulk powder. Typically, powder
masses with an extremely wide particle size distribution or diverse physical properties
are highly likely to be heterogeneous, which may result in high levels of variability
and samples that do not represent bulk mass. Moreover, powder characteristics
may change because of the attrition and segregation during transfer that can make
sampling extremely diffi cult.
It is well accepted that two types of sampling errors are possible when removing
small masses of powder from bulk [5] .
1.
2.
POWDER CHARACTERIZATION TECHNIQUES 1171
Segregation errors, which are due to segregation within the bulk and can be
minimized by suitable mixing and the use of a large number of incremental
samples to form a larger test sample.
Statistical errors, which arise because the quantitative distribution in
samples of a given magnitude is not constant but is subject to random fl uctuations.
Consequently, it is an example of a sampling error that cannot
be prevented but can be estimated and indeed reduced by increasing the
sample size.
Therefore, sampling procedures are of the greatest importance in order to reduce
the effect of nonuniform size segregation and nonrandom homogeneity of a system
to achieve statistically meaningful sampling results. Careful attention and faithful
observance must be demonstrated and it is extremely important that sampling
occurs when the powders are in motion [6] and samples are withdrawn from the
whole stream for equal periods of time, rather than part of the stream for all of the
time [3] .