Granulation and techniques
- 1. Chunilal Bhawan (Adjacent to BCPL),168, Maniktala Main Road · P.O. Bengal Chemicals, P.S. Phoolbagan · Kolkata – 700054
- 2. Contents Introduction Objective of granulation Essential properties of granules Method of granulation Modern equipment in granulation technology
- 3. Introduction Granulation, derived from the Latin word granulatum, meaning grain, is a process of enlargement of powdered particles to form grain-like agglomerates. In the pharmaceutical industry, the granules formed from the particles of the active pharmaceutical ingredient (API) and excipient mix are further processed effectively into solid dosage forms, such as tablets and capsules, or multiparticulates, such as pellets, beads, or spheroids to be filled into capsules or packed as sprinkle formulations. These granules offer the advantages of favorable size distribution, improved bulk density, and flow properties that further prevent the problems of caking, segregation, and poor tableting performance in the downstream processing.
- 4. Objective of Granulation To improve the compaction characteristics of the mixture. It also helps to minimize segregation risk. To improve the flow characteristics To produce uniform mixture To produce dust free formulation To improve bulk density It offers better content uniformity
- 5. Essential Properties of Granules Granules should have- Spherical shape Smaller particle size Optimum moisture content(1-2%) Good flow Good compressibility Sufficient hardness Have particle size in the range of 0.2-4.0 mm
- 8. Recent progress in wet granulation 1. Reverse wet granulation 2. Steam Granulation 3. Moisture-Activated Dry Granulation (MADG) 4. Thermal Adhesion Granulation (TAG) 5. Melt granulation 6. Freeze granulation 7. Foam granulation
- 9. Equipment used in Granulation Technology Oscillating granulator Gral mixer processor Fluidized bed granulator Double cone granulator Diosna mixer granulator Dau nauta mixer processor Topo vacuum processor Chilsonator or roller compacter
- 10. Oscillating granulator Whether it be a wet powder or a pack of dry block materials, the Oscillating Granulator will develop the material into fine and consistent granules. The machine comes with an elastically adjustable wire screen mesh that is easy to assemble and disassemble. The main elements of the machine are composed of an enclosed steel plated body and a lubrication system that enables it to run smoothly without producing any unnecessary noise. The Oscillating Granulator currently has five models to date and each with different features and output capacity
- 11. Oscillating Granulator works based on a mechanical granulation process the material is pressed through a specially designed sieve shaped like a rotor-arm to achieve the needed particle size requirement The granulating process is improved by the sieve continuous oscillating motion that applies a back and forth pressure to even out the required size distribution of force to the granules. Only accurately sized particles can pass through the sieve. The finished particle granules will then be released into a barrel-like container through the discharging hopper
- 12. Production capacity can be 5 to 1500 kilograms per hour. 55 rounds per minute are the standard rotary drum rotation speed It can rotate at a 360° angle The rotating drum diameter is 60 to 350 millimeter. All the components of this machine adheres to GMP standards.
- 13. Advantage- Made out of high-grade stainless steel plates Easy to clean and maintain Can be easily operated even with minimal supervision Produces large and consistent outputs at a time with less noise Suitable for granulating both dry and wet materials Flameproof and safe to use Easy machine installation and setup Conforms to Good Manufacturing Practice (GMP) standards.
- 15. Gral mixer processor First introduced in 1975, the Gral high shear mixer granulator is a fine example of GEA's experience in manufacturing high quality equipment for the pharmaceutical industry. High shear granulator range are multi-purpose processors, equally suitable for the high speed dispersion of dry powders, aqueous or solvent granulations, effervescent products and melt pelletization. Two versions of the top-driven high shear granulator are available: Gral and UltimaGral.
- 16. Standard features Top driven mixer and chopper: No seals in direct contact with the product Unique bowl design for optimal granulation Full opening discharge for easy unloading of difficult products Free standing machine Easy to wash-in-place Built to GMP-standards Removable bowl concept: A bowl trolley is available for easy removal of the bowl Twin speed chopper and mixer Full interlocked guarding Easy access for maintenance Video monitoring of the process
- 18. Fluidized bed granulator The powder particles are fluidized in a stream of air. Granulation fluid is pumped from a reservoir and sprayed from a nozzle on to the bed of powder Heated and filtered air is blown through the bed of unmixed powder to fluidize the particle admix the powder. The fluid causes the primary powder particles to adhere when the droplets and powder get collide. Sufficient liquid is sprayed to produce granules of the required size at that point the spray turned off but the fluidizing air continued.
- 19. The wet granules are then dried in the heated fluidizing air stream. Advantages- 1. It reduces product loss 2. Uniform drying 3. Fully automated 4. 2-6 times Greater heat transfer than tray dryer Disadvantages- 1. Expensive 2. Time consuming
- 21. Double cone granulator Its principle based on double cone mixer. The whole unit is rotated along axis. This blender supplied with vacuum which is ultimately reduce atmospheric pressure. Blades are present inside the double cone, for granulation. It is very advantageous for heat liable granules. The conical shape at both ends enables uniform mixing and easy discharge. Double Cone Blenders are most often used for dry blending of free flowing solids. Normal cycle times are typically in the range of 10 minutes
- 23. Diosna mixer granulator The machine have a stainless steel mixing bowl containing three blade impeller and auxiliary chopper blade. The main blade rotation about to 150-300 rpm. The speed of chopper blade is about 1500-3000rpm. The high shear wet granulation process can be divided into five stages- 1. Powder mixing 2. Binder addition 3. Nucleation 4. Growth of granules 5. Granule attrition
- 25. Nauta Mixer Processor Nauta Mixers (also called Conical Screw Mixers) make use of a conical chamber with a vertical screw that mixes the powder. The typical speed of the central screw is 70 to 80 Rpm It provide gentle mixing action and minimal heat generation. Its have many application, given below- 1. Mixing of free flowing powders 2. Moistening of powders 3. Coating 4. Granulation 5. Drying of powders 6. Mixing of slurries
- 27. Topo Vacuum granulator It was developed in Austria for the preparation of granules and coated particles under high vacuum condition The material placed in chamber which must be dust free suction, and the compartment is loaded by vacuum, granulating fluid with some additional materials as well. Under vacuum condition granulation force are increasing eventually, to produce necessary compaction. After that agglomerated particles dried under vacuum in chamber.
- 28. The main advantages of this equipment is that it required less granulating fluid than others. Hermes Pharma was a pioneer in applying TOPO vacuum granulation. This procedure comprises a synthetic granulation to enlarge the particles and increase their stability The TOPO granulation is a process utilized for the manufacture of effervescent granulate
- 30. Chilsonator or Roller Compacter This is mainly used for dry granulation process. Formation of dry granules mainly required dry powder for densification as well for agglomeration. This provides tremendous control of the final particle size and density. the product compacted by the Chilsonator must be granulated to a uniform particle size distribution. The basic concept of compaction is to force fine powders between two counter rotating rolls.
- 31. Some of the factors controlling the compaction process are- 1. Roll Surface Diameter, 2. Peripheral Speed, 3. Separating Force Or Pressure Capabilities, 4. Feed Screw Design, And 5. Material Being Processed. Advantages- 1. For thermo labile drugs 2. Moisture sensitive drugs like aspirin and vitamins 3. Those drugs which is not well compressed by wet granulation