FLOWABILITY

LILI FITRIANI
uhttps://www.youtube.com/wat
ch?v=ccc26E3fZo
Introduction
u Approximately 80% of pharmaceutical products and the
ingredients required for their manufacture are in powder form
u Many of these processes require good, consistent and
predictable flow to ensure quality products.
u The solid dosage form (tablets and capsules) is manufactured
by either dry-blending of fine powder ingredients or
combining the ingredients in a wet granulation step, followed
by drying.
u Various powder flow problems are commonly encountered in
industries handling fine powders.
Powder Flow

The concept of powder flow can be defined as the

relative movement of particles amongst adjacent particles
or along a containing surface

Factor influences powder flow à Inter-particle Forces

a. Van der Waals Forces
b. Capillary Forces
c. Solid Bridging
d. Electrical Interactions
e. Mechanical Interlocking
Factor influences powder flow: Inter-
particle Forces
u The so called “stickiness” of powders is the result of adhesive and
cohesive contacts between adjacent particles or containing
surfaces.
u Adhesion is defined as the attractive forces between dissimilar
materials
u Cohesion is defined as the attractive forces between similar
materials
u For fine powders, the sum of these inter-particle interactions
exceeds the driving force for flow, gravity in most cases
u The primary inter-particle forces are: van der Waals forces, capillary
forces, solid bridging, electrostatic forces and mechanical
 a. Van der Waals Forces
u Van der Waals forces are molecular forces that stem from
instantaneous electrical dipoles in atoms and are thus innate
forces.
u Van der Waals forces occur between all particles
u Hamaker, 1937 developed a model for determining the strength
of the van der Waals force between two macroscopic bodies by
summing all the molecular van der Waals force within the two
macroscopic bodies.

u The van der Waals forces can be reduced by increasing the

distance between the interacting particles
b. Capillary Forces
u Voids between neighbouring particles act as very fine
capillaries where moisture from the atmosphere can
condense – even at low relative humidity (RH) and ambient
temperatures

u Capillary forces are generally regarded as very strong forces.

u Capillary force dominates the other adhesive forces at relative
humidities above 65%, with themaximum effect at 100% RH
 c. Solid Bridging
u If a liquid bridge exists, the surfaces of the particles can dissolve until
the solubility of the material is reached.
u If drying subsequently occurs, perhaps due to small changes in relative
humidity, recrystallization of the solute takes place, thus physically
linking adjacent particles together
u Thus it is not uncommon to find the presence of solid bridging following
the formation of liquid bridging
 d. Electrical Interactions
u When two charges approach one another, the charges will either
attract one another in the case of opposite charges or will repel one
another in the case of same charges
u The amount of charge at the two surfaces determines the overall
strength of the electrical force.
u However, the amount of excess charge on the surfaces of particles
does not remain constant over time.
u As time increases, for a static particle, the charge diminishes thus
resulting in reduced electrical forces.
u In addition, if either of the contacting materials are conductive or if
water is present in the voids, the charge will also decay resulting in
reduced electrical forces
e. Mechanical Interlocking
u Real surfaces are rarely truly smooth – there will be some form of asperity, even if
it is on a nanometre scale.
u Due to such asperities, when two surfaces are in contact the peak of one surface
may align directly in the trough of the other surface as depicted in Figure
u This interlocking of surface, known as mechanical interlocking,hinders the relative
movement of adjacent particles and thus inhibits powder flow
A comparison between the van der Waals force, the capillary force and the
electrical forces
FLOW MEASUREMENTS

u Powder Densities and their Indices

u Powder Avalanche
u Angle of Repose
u Flow Through an Orifice and the Critical Orifice Diameter
u Powder Rheometer
u Shear Cells
A. Powder Densities and their
Indices
u When a powder is poured into a container, it will occupy a given volume which
can be termed the initial volume (V0)
u This occupied volume is dependent on the spatial arrangements of the
individual particles.
u The ratio of the mass of powder to the occupied volume (V0) is known as the
bulk density, ρb, or the initial or poured density.
u If the container is disturbed by, for instance, tapping, the energy applied from
the taps (provided the energy is sufficient) will break and re-form the inter-
particle contacts of the powder.
u The result is the powder forms a more consolidated state and the volume will
consequently decrease to a new volume, Vn, where n is the number of taps
u As n increases, a limit is reached and no further consolidation occurs
u Because the mass of the powder remains constant, a new density is obtained,
which is termed the tapped density, ρt, or the final density.
• Bulk and tapped densities on their own are
not indicators of powder flow
• In 1965 Carr noted a relationship between
the bulk density, and the tapped density à
Carr index (CI)
• Hausner in 1967 noticed the same
relationship and defined the quotient of the
tapped density and the bulk density as the
Hausner ratio, HR:
q The United States Pharmacopeia (USP38-NF33
Chapter 616) provides guidelines to measure both
the bulk and tapped densities.
q However, because these guidelines recommend
either the use of relatively large amounts of sample,
the smallest of which is 100 g, or to fill relatively large
containers, the smallest of which is 25 cm3, these
guidelines may not be readily suitable for
applications where only relatively small amounts of
samples are available such as when investigating
novel pharmaceutical systems.
b. Powder Avalanche

u Powder avalanching is most commonly carried out in a rotating

cylinder type apparatus with either a photocell array behind the
rotating cylinder or a digital camera to detect avalanches.

u However, the reality is there are a number of possible flowpatterns a

powder can have within a rotating cylinder: slipping,slumping,
rolling, cascading and cataracting
q Due to the chaotic nature of avalanching, it is
not possible to predict the magnitude of each
avalanche. Instead, the time (or weight) of each
avalanche is often, like with many chaotic
processes, presented as the so-called “strange
attractor plot”, where tn(or Wn) forms the
abscissa while tn+1 (or Wn+1) forms the ordinate.
q Here, the points for the time (or mass) of
consecutive avalanches are recorded and
joined together until the end of the experiment
q The flowability of a powder is therefore
described by both the MTA (mean time to
avalanche) and the “deviation” of the strange
attractor plot
q Generally, for a good flowing powder, a small
scatter along with a small MTA value is obtained
while the opposite is true for poor flowing
powders where a large MTA value and a large
deviation is obtained
c. Angle of Repose (AoR)

u The angle of repose (AOR), or sometimes referred to as the “repose

angle”, is defined as the inner angle, measured from the flat
horizontal surface to the free sloping edge of the cone-like pile
u The static angle of repose is so named due to the static nature of
the experiment à fixed funnel and free standing cone (USP38-NF33
Chapter 1174)
u In the “fixed funnel and free standing cone” method, the powder is
poured through a funnel that is at a fixed height above a flat
horizontal surface.
u The pile is built up until its apex just reaches the bottom of the funnel.
 u Angle of repose, α, and can be calculated from equation:

Where:
h is the vertical distance between the base of the pile to
the apex
r is the radius of the base of the pile.
d. Flow Through an Orifice and the
Critical Orifice Diameter
u Flow through an orifice was traditionally measured discretely by
measuring either the time required for a given mass/volume of
powder to flow through the orifice or the mass/volume of powder to
flow through the orifice in a given time period
u The mean flow rate can then be calculated either as mass or
volume per unit time.
u The greatest limitation of such measurements is the inability to profile
any inconsistent flow patterns of the powder
à the use of an electronic powder flowmeter which utilized a
calibrated electronic strain gauge connected to a chart recorder
e. Powder Rheometer
u The apparent “rheological” properties of powders
u In the example of the FT4 Powder Rheometer®, a helical blade is used. The
instrument works by continuously measuring the required torque to rotate the blade
at a constant rate as the blade is moved through the powder either in the
downward or upward direction.
u In general, the more cohesive the powder, the more torque is required to
continuously rotate the blade at a constant rate through the powder.
u This is because cohesive powders contain stronger inter-particle forces and higher
friction between adjacent particles; ergo the powder provides more resistance to
flow.
u The opposite is true for free-flowing powders. That is, free-flowing powders have
weaker inter-particles forces and lower friction between adjacent particles and thus
require less torque to cause the powder to flow.
u FT4 system à One of the advantages claimed for the FT4 system is the automated
pre-conditioning of the sample prior to testing
f. Shear Cells – FT 4
u Jenike recognized the importance of the consolidation effect on powder flow
and also the lack of flow measurements that took such considerations into
account
 POWDER FLOW AND THE
MANUFACTURING/
PERFORMANCE OF
PHARMACEUTICAL PRODUCTS
A. Capsule Filling

Video
u Wet Granulation
c. Tablet Manufacture by Direct Compression
d. Performance of Dry Powder Inhalers
CONCLUSION…???