Pharmaceutical Manufacturing Handbook: Production and

906 PHARMACEUTICAL PREFORMULATION
properties (brittleness, elasticity), density, size, shape, surface area, moisture content,
direction and rate of shear, storage container dimension, and particle – wall interaction
[19] .
It is a property of all powders to resist the differential movement between particles
when subjected to external stresses. A bulk powder is somewhat analogous to
a non - Newtonian liquid, which exhibits plastic fl ow and sometimes dilatancy if the
particles being infl uenced by attractive forces. Accordingly, powders may be free
fl owing or cohesive ( “ sticky ” ). The resistance is to free fl ow is due to the cohesive
forces between particles [18] . Three principal types of interparticular forces are
forces due to electrostatic changing, van der Waals forces, and forces due to moisture.
Electrostatic forces are dependent on the nature of the particles, in particular
their conductivity. Van der Waals forces are the most important forces for most
pharmaceutical powders. These forces are inversely proportional to the square of
the distance between the two particles and hence diminish rapidly as particle size
and separation increase. Powders with particles below 50 μ m will generally exhibit
irregular or no fl ow due to van der Waals forces. Particle shape is also important;
for example, the force between a sphere and a plane surface is about twice that
between two equal - sized spheres. At low relative humidity, moisture produces a
layer of adsorbed vapor on the surface of particles. Above a critical humidity, typically
in the range 65 – 80%, it will form water liquid bridges between particles. Where
a liquid bridge forms, it will give rise to an attractive force between the particles
due to surface tension or capillary forces. The role of the formulator is to ensure
that the fl ow properties of the powder are suffi cient to enable its use on modern
pharmaceutical equipment, powder hoppers, and fl ow through orifi ces in the tablet
production.
It is important that the powder fl ows from the hopper to the fi lling station of the
tablet machine at an appropriate rate and without segregation occurring. There are
two types of fl ow that can occur from a powder hopper: core fl ow and mass fl ow [2] .
Figure 6 shows the two different powder fl ow patterns in hoppers. When a small
amount of powder is allowed to leave the hopper, there is a defi ned region in which
downward movement takes place and the top surface begins to fall in the center. A
core fl ow hopper is characterized by the existence of dead spaces during discharge.
A mass fl ow hopper is one in which all the material is in motion during discharge,
in particular the areas adjacent to the hopper wall. As a small amount of powder is
discharged, the whole bulk of the powder will move downward. Whether core fl ow
or mass fl ow is achieved is dependent on the design of the hopper (geometry and
wall material) and the fl ow properties of the powder.
Powder fl ow into orifi ces is also important when fi lling dies in tablet machines
and in certain types of capsule - fi lling machines. For a given material, the fl ow into
or through an orifi ce is dependent on the particle size (Figure 7 ). In general, as the
particle size increases, the powder fl ow rate also increases. However, there is practically
no fl ow if the particle size is below 50 μ m or above 1200 μ m. The Carr index
gives us the guidance for powder fl owability. A lower Carr index of excipients is
more desirable for acceptable powder fl ow. At the lower end of the particle size
range, cohesive forces will result in poor fl ow. Powders with particles below 50 μ m
will generally exhibit irregular or no fl ow due to van der Waals forces. As the particle
size increases, the fl ow rate increases until a maximum is achieved, at an orifi ce
diameter – particle diameter ratio of 20 – 30. As the particle size continues to increase,