Foam Granulation part 1

Due to changing philosophies towards continuous developing, new equipment has been introduced
into pharmaceutical production facilities. The twin-screw extruder can be an example of such
equipment for make use of in wet granulation. The authors review developments in wet granulation
utilizing a twin-screw extruder; construct the problems with wetting in this machine; and introduce
a novel technique, foam granulation, that uses the twin-screw extruder to fully satisfy the unique
needs of granulation.
double screw extruder
The twin-screw extruder provides highly consistent granulates due to its continuous operation and
closely confined flow path, which requires that all particles experience a similar shear history. The
intensive mixing of the twin-screw extruder allows lower optimal liquid focus for granulation while
developing denser granules for both placebo formulations and highly dosed drugs compared to a
high-shear batch mixer. As a result, drying and milling operations could be significantly reduced
with usage of this machinery in solid oral-dosage production.
The binding liquid in wet granulation has a profound influence on product granule properties and
affects the friction between conveyed powders and the barrel wall inside the extruder, which affects
power consumption and the exiting temperature of granules. You can find crucial concerns to be
solved in regards to introducing liquids into this kind of machinery to acquire rapid and uniform
wetting of excipients so that the process exhibits steadiness in operation, boundaries become
lubricated to reduce equipment wear and granule heating immediately, and top quality granulates
are obtained.
A regular variant of extruder used for granulation is the intermeshing fully, co-rotating twin-screw
extruder. Differences between vendors are largely based on the available internal volume of the
machine plus the screw diameter, both of which can affect granulate real estate in both granule size
and intragranular porosity significantly. The machine is modular highly, making it a flexible system
for constant manufacturing of different products during its lifetime of system to a company. The
intermeshing area between your two screws creates a self-wiping actions that minimizes material
accumulation within the machine but also provides a complex flow course for powders to combine
and consolidate. For wet granulation, the die end of the extruder is normally available to collect
granules without substantial consolidation.
Wet granulation inside the co-rotating twin-screw extruder is a starve-fed procedure, meaning that
the available internal volume of the machine is under no circumstances completely filled up with
material during operation. This modus operandi is essential to extrusion since it minimizes
dissipative temperature build-up in conveyed drug formulations as it limits compression against the
barrel wall, it decouples the parameters of output price and screw speed to provide formulators even
more control over their procedure, and it more readily allows the downstream addition of supplies
because the system is not pressurized aside from small mixing regions. The zones of the screws that
are starved knowledge dominant drag flow, in which powders are pushed downstream by the
rotating flights of conveying-type elements. These screw elements have been seen to contribute little
to granule growth. Actually, screw designs only using conveying elements show very poor
distribution of the binding liquid within exiting solids. It is rare, however, that a screw design is
completely comprised of conveying factors or that the complete length of the machine is ever totally
starved. Significant granule growth necessitates the inclusion of pressure-driven mixing zones,

which are fully filled as powders are squeezed through these sections necessarily. Kneading blocks
and comb elements are examples of mixers popular in sparing numbers across the screw length to
produce granule growth alongside minor attrition. Keeping these mixing elements nearer to the end
of the extruder reduces attrition.
Powder flow level is one of the most significant parameters influencing the extent of granule
development, with higher outputs producing much larger granules. The effect is brought on by the
higher volumes of powder that build-up in front of pressure-motivated mixing zones as stream rate
increases, producing bigger axial compressive forces on the contaminants present. In fact, it's been
found that the dispersion of binder within poorly wetted mass could be increased for granulation if
the screw design and flow pace are adjusted to supply suitable compressive forces. The influence of
flow charge on granule growth, nevertheless, is not seen in smaller extruders or highly starved
techniques often. Increasing screw speed has less effect on granule size but generally escalates the
amount of chopping events provided by mixing zones to reduce the occurrence of oversized
contaminants. For a fixed flow rate, increasing the screw speed shall reduce the level of powder that
fills the conveying screw elements, resulting in lower power intake by the process.
Among the published research for wet granulation, a crucial point that is mentioned, yet widely
known to the pharmaceutical industry, is the difficulty of uniformly wetting a formulation in an
extruder. The problem arises as a result of earlier mentioned confined space inside the extruder
closely, which results in the liquid injection port getting in quick proximity to the powder flow. This
confinement prevents atomization of the binder resolution into micro-sized droplets ahead of
contacting the powder solids, as is done in high-shear batch mixers. Therefore, regions of the
powder turn into oversaturated while some remain virtually dry. This matter was highlighted in the
industrial-oriented document by Shah, who reported method surging, though engine overload events
are likewise common. Shah demonstrated several tactics linked to screw design and the sequential
addition of small liquid quantities in to the process as means to minimize surging occurrences. Such
alterations greatly raise the complexity of functioning the extruder and do not eliminate the root
reason of the issue. Alternatively, a new solution called foam granulation uses the initial behavior of
aqueous foam to cause rapid spreading of the binding liquid over a big section of the powder during
wetting.