ADVANCE GRANULATION TECHNIQUES

WHAT IS GRANULATION?

❑Granulation, the process of particle enlargement by agglomeration

technique. Granulation process transforms fine powders into free-
flowing, dust free granules that are easy to process compress, packed to
use etc.

Or

❑Decrease the surface area of the sensitive API for further process,
transportation, handling, compression etc. Granules used in the
pharmaceutical industry have particle size in the range of 0.2- 4.0 mm
WHY GRANULES ARE PRODUCED?

➢ Granules are produced to enhance the uniformity of the APl in the final
product.
➢ Improve flow property and compression characteristics;
➢ To increase the density of the blend so that it occupies less volume per
unit weight for better storage and shipment;
➢ To facilitate metering or volumetric dispensing
➢ To reduce dust during granulation process to reduce toxic exposure and
process-related hazards
➢ To improve the appearance of the product.
➢ To control the rate of drug release
CHARACTERISTICS OG GRANAULES

➢ Spherical shape for improved flow; narrow particle size distribution for
content uniformity; volumetric dispensing
➢ Sufficient fines to fill void spaces between granules for better
compaction and compression;
➢ Adequate moisture and hardness to prevent breaking and dust
formation during process.
CHARACTERISTICS OG GRANAULES

➢ Particle size of the drug and excipients;

➢ the type, concentration, and volume of binder and solvents;•
➢ granulation time;
➢ type of granulator;
➢ drying rate (temperature and time), etc.
PNEUMATIC DRY GRANULATION (PDG)

Pneumatic dry granulation (PDG), an innovative dry

granulation technology, utilizes roller compaction
together with a proprietary air classification method to
produce granules with extraordinary combination of
flowability and compressibility.
PNEUMATIC DRY GRANULATION (PDG)

In this method, granules

are produced from powder particles by initially applying
mild compaction force by roller compactor to produce a
compacted mass comprising a mixture of fine particles and
granules.

The fine particles and/or smaller granules are

separated from the intended size granules in a fractioning
chamber by entraining in a gas stream (pneumatic
system), whereas the intended size granules pass through
the fractioning chamber to be compressed into tablets.
PNEUMATIC DRY GRANULATION (PDG)

The entrained fine particles and/or small granules are

then transferred to a device such as a cyclone and are
either returned to the roller compactor for immediate re-
processing (recycling or recirculation process) or placed in
a container for reprocessing later to achieve the granules
of desired size.
PNEUMATIC DRY GRANULATION (PDG)
PNEUMATIC DRY GRANULATION (PDG)

PDG technology could successfully be used to produce

good flowing granules for any formulations that produce
compacts with a tensile strength of ~ 0.5 MPa. Also, this
technology enables the use of high drug loads of up to
70-100%, because sufficient flowability could be achieved
even at lower roll compaction forces (lower solid fractions)
compared to usual roller compaction.
PNEUMATIC DRY GRANULATION (PDG)
TECHNOLOGY OF FOAMED BINDER (FBT)

Using familiar, proven METHO CEL polymers. In this technology greatly

improves binder distribution in the formulation mix and yields a
remarkable array of processing advantages.
HOW FOAM BINDER GRANULATION WORKS:

A simple foam generation apparatus is used to incorporate air into a

conventional water- soluble polymeric excipients binder such as
METHOCEL hypromellose ( hydroxypropyl methycellulose).
In a small- scale laboratory setting or in a full- scale production setting, the
foam generator can be connected directly to high-shear, low- shear, or fluid
bed granulation equipment.
EXTREMELY EFFICIENT PARTICLE COVERAGE
AND BINDER DELIVERY

Foam binder performance is rapid and extremely efficient particle coverage

compared to sprayed liquid binders.
It is offer much higher surface area and they spread very rapidly and evenly
over powder surfaces.
it is also shows also soak: spread ratio, so particle surfaces are quickly and
completely covered.
By contrast, spraying is a cumulative process that begins with small liquid
droplets dappling particle surfaces until enough binder liquid accumulates
to initiate particle agglomeration.
ADVANTAGES:

• This process can shorten processing times by reducing water

requirements.
• It can improve reproducibility through more uniform binder
distribution.
• Foam processing also offers better end point determinations and
reduced equipment clean-up time.
• This technology does not demand new equipment or radical
changes in processing techniques.
• You can very easily use it with familiar high, low shear, or fluid
bed granulation equipment, in both laboratory- and production –
scale setting.
ADVANTAGES:

• Foam granulation takes advantage of the tremendous

increase in the liquid surface area and volume of
polymeric binder foams to improve the distribution of the
water/ binder system throughout the powder bed of a
solid dose pharmaceutical formulation.
• Overall, foam binder processing is easier, faster, and
allows safer handling of potent drug compounds.
STEAM GRANULATION
INTRODUCTION

 Steam Granulation which is a modification on wet granulation.

 Steam is used as a binder instead of water
 In steam generation as a new wet granulation technique, water steam is used as binder instead of traditional liquid
water as granulation liquid .Steam, at its pure form is transparent gas, and provides a higher diffusion rate into the
powder and a more favorable thermal balance during the drying step. After condensation of the steam water
forms a hot thin film on the powder particles, requiring only a small amount of extra energy for its elimination
and evaporates more easily.
STEAM GRANULATION METHOD

 An equipment such as high-shear mixer coupled with a steam generator would be enough for this technique.
 However, this method requires high energy inputs from steam generators.
 Besides, this process is not suitable for all binders and is sensitive to thermolabile drugs.
 The granules produced by this process have higher dissolution rate due to the increased surface area of the
granules compared to conventional wet granulation processes.
STEAM GRANULATION-SCHEMATIC DIAGRAM
ADVANTAGES

 Uniformly distribution the powder particles.

 Higher distribution rate of granules because of larger surface area generated.
 Time efficient.
 Maintain sterility.
 A higher diffusion rate into powders and more favourable thermal balance during drying.
DISADVANTAGES

 Requires special equipment for steam generation and transportation.

 Requires high energy inputs.
 Thermolabile materials are poor candidates.
 More safety measure required.
FREEZE GRANULATION TECHNOLOGY
HISTORY

 Freeze granulation was first developed for granulation of ceramic powders at Swedish Ceramic Institute (SCI) in
Göteborg in the late 1980's.
 During the 1990'S, Freeze Granulation was successfully applied in material and processing developments within
many research projects and commercial contract work.
 However, no commercial equipment was available and therefore PowderPro AB was founded in January 2000 with
the objective to provide wet granulation equipment for the Freeze Granulation process
HOW IT WORKS?

 Freeze granulation is an industrial process of producing spherical granules with excellent fluidity by spraying a
liquid material under ultra-low temperature environment.
 The sprayed raw material instantaneously gets frozen and dried granules are obtained after sublimation (freeze
drying) process.
 Granules produced by freeze granulation are spherical and have excellent fluidity and can maintain high
homogeneity.
CHARACTERISTICS:

 Spherical granules with excellent fluidity

 No transfer of fine particles and binder
 Low density and soft granules
 Uniformly dispersed granules without becoming hollow
 Less material loss and high yield
 Low possibility of contamination
ADVANTAGES

 The granule density can be controlled (solid content of the slip)

 No cavities in the granules
 No migration of small particles and/or binder gives a high degree of granule homogeneity
 A mild drying procedure minimizes oxidation of non-oxides and metals
 Lower specific granule density and evenly distributed pressing aids gives softer granules and ensure that all
granules are broken during compaction
APPLICATIONS:

 Granulation for powder pressing (ceramic and metals)

 Material synthesis with high yield
 Preparation of easy re-dispersible nano powder or graphene
 Production of carrier particles for various catalysts
 Production of high performance particles for thermal spraying
 Pharmaceutical and biomaterial applications