WHAT IS GRANULATION:
Granulation is the process of forming granules (i.e. compacted group of particles) by application of forces of attraction amongst the particles within the mixture. These forces could be adhesive (bond formation between the molecules of dissimilar materials ex. water with solid), Or cohesive (bond formation between the molecules of the same Or similar materials ex. solid with solid), Or Vanderval's forces of attraction (i.e. the not-so-strong electrostatic forces between atoms or molecules). Important point to be noted here is that the process of Granulation should be verifiable, repeatable and should always give consistent results every time.
In this blogpost, we will discuss granulation in the Pharmaceutical Formulation point of view.
WHERE AND WHY IS GRANULATION REQUIRED:
Granulation ensures or aim at attaining uniformity of the material mixture. Many a times (especially true in case of pharma manufacturing) it is utmost important that each small group of particles should contain right proportion of all the components. In other words, each granule Or a group of compacted particles should be a representative (in terms of the uniform composition) of the overall mass.
ADVATNGATES OF GRANULATION:
Some of the important advantages of the Granulation Process are as follows:
# Granulation ensures uniform distribution of each component of the mass, thereby achieving proportionate composition of the granule. In simple language one can say that, each granule acts as a representative sample of the entire mass Or mixture.
# Granulation increases the flow ability (or flowability) of the feed material.
# Granulation binds the particles together, thus increasing the density and reducing the dusting during the operation.
# Granulation helps in producing the quality tablets which are helpful in achieving the desired effect after consumption by human.
GRANULATION PROCESS AND MECHANISM:
Usually, this can be achieved by either a Wet Granulation method Or a Dry Granulation method. Wet granulation involves addition of a liquid with Or without a binding agent. Whereas, incase of a Dry Granulation, the particles are subject to a high pressure, thus gets attached to each other forming a not-so-strong solid like structure.
Many theories on forces of attraction helping the granulation process has been published worldwide such as Formation of Solid and Liquid Bridges, Partial Melting and Re-crystallization, Mechanical Interlocking between the particles etc. To facilitate these processes (especially in case of a wet granulation), the concept of High Shear Granulation comes into picture.
INTRODUCTION TO RMG (RAPID MIXER GRANULATOR):
As the name suggests, an RMG facilitates formation of granules from the powder mass by mixing the powder particles, wetting the powder particles with the help of the granulating liquid or binder, attaining spheronization, making the granules denser and hence stronger etc.
The powder particles are forced to undergo a pattern of mechanical actions such as rising, tumbling and whirling. Due to the repetition of these actions and in the presence of the liquid or a binder, the particles develop the bonding for each other, thus, forming the grain like shape.
MAJOR COMPONENTS OF AN RMG (RAPID MIXER GRANULATOR):
1. Mixing Bowl: This is a vertical cylindrical vessel with slightly conical top with a flat bottom with an agitator shaft protruding inside the bowl. The L/D ratio of this stirred tank vessel is much lesser than one, as D is much larger than L. This is because the powder Or mass to be mixed needs sufficient area for rising, tumbling and whirling while rotating around the vertical axis.
The Top Lid Or Cover is usually hinged to the bowl. However, it can also be of hydraulically liftable type. A good quality high density sealing gasket is used to seal the top lid flange with the bowl flange tightly. Sometimes, an open Or a gritted nozzle is provided on the top nozzle for easy charging of raw material Or binder solution etc.
In tank WIP (wash in place) nozzle can be provided optionally.
2. Impeller Assembly: The agitator is always a bottom entry one (meaning the motor driven shaft protrudes the bottom of the vessel inside) with the blades rotating parallel to the flat bottom. The blades are specially designed and angled such that they slightly lift the mass and allow it to jump across the blade. At the same time they keep pushing the solid mass bed. This constantly keeps the mass in action and undergo rising-falling-tumbling. Due to the rotational motion, slowly the particles that coalesce start gaining spherical shape.
A good quality bearings and sealing mechanism is used to avoid any kind of powder leakage from the entry point of the agitator.
The Rotational Speed (RPM) of the agitator can be controlled with variable frequency drive.
The blades assembly can be dismantled for cleaning Or maintenance purpose.
3. Chopper Blades: A high speed lump breaker Or chopper assembly is provided in the laterla direction inside the bowl. The shaft of the lump breaker protrudes the cylindrical wall of the bowl inside the vessel and has knifes places on the shaft specially designed to break the bigger lumps formed due to addition of liquid or binding agent in the rotating mass.
Again a good quality sealing mechanism is used to avoid powder leakage from the entry point of the lump breaker.
4. Pneumatically operated granule mass discharge system: Just like the chopper assembly, another nozzle (slightly bigger in size) is provided on the lateral side (i.e. on cylindrical wall of the vessel) closer to the bottom. This nozzle has a plunger type valve, which is pneumatically operated. When the granulation is on, this valve is flushed to the curvature of the opening of the bowl. However, at the time of discharging the material, the plunger moves axially making way for the granules to enter the nozzle and get removed from the Y type branching.
Many a times the Y type branch has a chute attached to take the granules to a vibrosifter or a conical mill.
5. Operating Platform and Ladder: The motor and gear assemblies are concealed under the operating platform which is at a height. Hence, a connected ladder with railing us provided for ease of material loading and supervision of the operation.
6. Operating Panel: In pharmaceutical formulations, many a times the granulation equipments are PLC -HMI controlled. However, the usual push button type relay based operating paenl are not uncommon too.
POINTS TO BE TAKEN INTO CONSIDERATION WHILE PLANNING AN RMG (RAPID MIXER GRANULATOR):
Some of the important points which are strongly related to RMG and require attention while planning for an RMG are as follows:
1. Capacity and Space Planning: RMG capacity should be planned based on the two most important parameters viz. (a) bottlenecking capacity of the entire granulation line (b) space availability.
Mostly RMG requires a very large area (due to operating platform and ladder). Also, many related operations are preferred to be carried out in the same area where RMG is placed such as Sifting, Milling (Co-Milling or Multimilling), Drying etc. Also, the Mass Mixer and Paste Kettle used prior to granulation too are placed in the same room at times.
Looking at all these, the space can become a bottleneck and hence the capacity Or batch planning may get affected.
2. Anciliary Equipments Planning: As discussed above, the capacities of the related ancillary equipments such as Paste Kettle, Blender, Dryer, Mass Mixer and other granulation line equipments Or mass transfer equipments such as Lifter- Loader etc must be planned carefully.
3. MOC and Surface finish: Depending on whether its a GMP or a Non-GMP operation, the material selection (MOC) is done. Unusually the surfaces are extremely smooth and the finish is of a high RA value, so as to avoid any opportunity of corrosion.
4. Ergonomic design: Every aspect of the design including the ladder, the railing, the top lid, material charging nozzle, the platform height, the discharge mechanism, the operating panel etc should be ergonomically designed. This is extremely important not only in operators' safety point of view, but also important in increasing their efficiency and raising the overall quality and output.
Please feel free to contact incase of any queries, questions Or suggestions on this Or any other topic at shg.techo@gmail.com
Post a Comment