Some factors can affect the efficiency of mixing leading to non-uniform distribution of materials which can result in inaccurate dosage production. These factors affecting mixing are as follows:
Factors Affecting Mixing
(i) Material density:
If the mixture components are of different densities, the denser material will
sink through the lighter one, the effect of which will depend on the relative
positions of the material in the mixer. To maximize mixing, the denser material
is placed at the lower layer in the mixer during the mixing process to enhance the
degree of mixing to an equilibrium state.
(ii) Particle size:
Different particle sizes in materials to be mixed can cause segregation that
leads to non-uniform distribution. The smaller particles fall within the voids
between the larger particles. During the mixing process, the particles in the bed
might dilate and the greater porosity of open packing allows a large particle
to slip into the void eventually resulting in non-uniform distribution. As the
particle size increases, flow properties also increases due to the influence of
gravitational force on the size. It is easier to mix two powders having
approximately the same particle size.
(iii) Particle shapes:
The particles with spherical shapes are easier to mix uniformly whereas other
shape particles face an increase in difficulty in the mixing process. The ideal
particle is spherical, and further, the particles depart from this theoretical
form, there is greater difficulty of mixing. If the particles are of irregular
shapes, then they can become interlocked leading to a decrease in the risk of
segregation once mixing has been achieved.
(iv) Particle attraction:
Some particles exert attractive forces due to adsorbed liquid films or
electrostatic charges on their surfaces and tend to aggregate. Since these are
surface properties, the aggregation increases as particle size decrease. The
interaction forces between drug and carrier surface are predominately van der
Waals’ forces, but electrostatic and capillary forces may also play a role.
These forces vary with the size, shape, crystallinity, hardness of the adhering
particle, surface roughness and contamination of the carrier particles, the
intensity and duration of shear forces during mixing, and the relative
humidity.
(v) Proportion of
materials: The proportion of substances in a given mixture is
one of the crucial factors that result in the efficacy of mixing. The
proportions of materials to be mixed play a very important role in powder
mixing. It is easy to mix the powders if they are available in equal quantities
but it is difficult to mix small quantities of powders with large quantities of
other ingredients or diluents. However, to ensure uniform mixing, the substance
should be mixed in geometric and ascending order of their weights.
(vi) Mixer volume:
In the mixing process, the mixer must reserve sufficient space for dilation of
bed during the mixing process. If this condition is maintained the powder
samples are getting enough space for the free mixing to achieve a uniform mix
with increased efficacy. Overfilling reduces the efficiency and may prevent
mixing entirely.
(vii) Mixing mechanisms:
The suitable and sufficient shear force and a convective movement is a prime
requirement for the mixer to ensure efficient mixing of bulk material. The
mixer selected based on its mechanism must apply suitable shear forces to bring
about local mixing as well as convective movement to ensure that the bulk of
the material passes through this area.
(viii) Mixing time:
Mixing must be carried out for an appropriate time so that the degree of mixing
will approach its limiting equilibrium value. Since there is an optimum time
for mixing of any particular mixture it must be noted that the equilibrium condition
may not represent the best mixing if there is segregation. While handling
uniformly mixed powders after completion of operation enough care needs to be
taken to avoid segregation. The vibration caused by subsequent handling,
transport, or during use is likely to cause segregation.
(ix) Method of handling:
When mixing is completed, the product is required to be handled according to
standard operating procedures to minimize the risk of segregation. A common
factor that causes segregation is vibration throughout the handling, transport,
or packaging. This results in the fact that all bulk powder should undergo
remixing before taking them into use.
(x) Nature of the
product: Rough surface of the powder components may result in ineffective
mixing. The active substances which are generally very fine in size may enter
into the pores and cavities on the surfaces of the other larger ingredients. If
such substances get adsorbed on the surface of other powders there is a decrease
in aggregation as well as segregation. For example, the addition of colloidal
silica to strongly aggregating zinc oxide help to maintain fine dusting powder
that can be easily mixed.
(xi) Mixing Conditions:
The theory of powder mixing shows four conditions that should be observed in
the mixing operation. Those conditions affect mixing.
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