Pharmaceutical Manufacturing Handbook: Production and

6.2.2.6 Powder Flow and Compressibility
The derived properties of a drug substance play a critical role in deciding about the
feasibility of a solid dosage form. These include the bulk density, fl ow properties,
and compressibility of the drug powder. Powder fl ow is infl uenced by many solid -
state properties, including crystal habit, bulk density, particle size, and shape. Bulk
density is an important determinant of powder fl ow. It is the ratio of a known weight
of the powder and its bulk volume. This is determined by pouring a weighed amount
of the powder into a graduated cylinder and measuring its volume. Bulk density is
particularly important for high - dose drugs, where the drug would occupy a major
portion of the tablet or capsule dosage form. The true density of a powder is determined
using a helium densitometer [31] . The volume of helium gas that passes
through an empty tube is compared with the volume of helium passing through the
tube when fi lled with a defi ned weight of the powder. The difference in the volume
gives the true volume of the powder, which is then used to calculate the true density
of the powder. This information can be used to calculate the porosity:
Porosity =
bulk volume − true volume
bulk volume
× 100 (1)
The porosity of a powder depends on particle size and shape; pharmaceutical
powders vary in porosity from 30 to 50% [31] . Powder with varying particle size will
give a porosity of less than 30%, where the small particles may occupy the pores in
between the larger particles. On the other hand, powder aggregates lead to increased
porosity and poor fl ow properties.
The powder fl ow is determined using the angle of repose or Carr ’ s index (Figures
9 a and b ). The angle of repose is the angle that the powder makes with the horizontal
surface when allowed to fl ow through a funnel (Figure 9 a ). This is based on the
principle that powder fl ow is infl uenced by the relative infl uence of interparticle
friction and the gravitational pull on the powder. Pharmaceutical powders have an
angle of repose of 25 ° – 40 ° [33] , and in general, a good fl owing powder will have a
lower angle of repose (Figure 9 c ). The angle of repose using the funnel provides a
good estimate of the infl uence of particle size, shape, and electrostatic interaction
between the particles when the powder fl ows through the hopper in a tableting
machine [34] . When there is a limited drug sample, Carr ’ s index is used to estimate
powder fl ow and compressibility. In this method, a small quantity of the powder is
used to determine its bulk density and this is followed by determining the tapped
density of the powder. After fi lling, the graduated cylinder is tapped on a hard
surface (3 – 30 taps) until the powder consolidates and gives a constant volume
(Figure 9 b ). Carr ’ s index is calculated using the equation
Carr’ s index =
PHYSICAL/BULK CHARACTERISTICS 949
tapped − poured density
tapped density
× 100 (2)
This index is a good measure of powder consolidation and compressibility for predicting
the feasibility of developing a tablet dosage form. A lower Carr ’ s index is
indicative of a good fl owing powder. There is a good correlation between angle of
repose and Carr ’ s index [Figure 9 c ], and depending on the quantity of the drug