GRANULATION and methods of granulation.pptx

This document provides a comprehensive overview of Granulation process involved in the formulation of tablets. It includes methods of granulation ( Dry granulation, Wet granulation, Direct compression) and the role of excipients. It details the the steps involved , advantages, and disadvantages of each granulating method. It also includes the equipments used in the process of granulation.

1. GRANULATION METHODS AND EQUIPMENTS Presented by: Gauri Warad

2. Granulation Granulation is the enlargement process in which primary powder particles are made to adhere to from larger, multi-particle entities called granules . Granules means small grain-like material. E.g., sugar and salt, etc. Granulation derived from the Latin word “ granulatum ”- grain. In pharmaceutical granules are small particle of a drug used to make tablet or capsule. It is a process used to make powder into granules, Which are easier to compress into tablet or capsule. Bonds are formed by compression or by using binding agents .

3. NEED FOR granulation To enhance flow of powders. To avoid weight variation. To produce uniform mixture. To avoid poor content uniformity. To improve compaction. To produce dust free environment. To avoid powder segregation.

4. Methods Used For Granulation

5. Dry Granulation Method The dry granulation process is used to form granules without using a liquid solution because the product granulated may be sensitive to moisture and heat. This method is also called as double compression method . Forming granules without moisture requires compacting and densifying powders . In this process the primary powder particles are aggregated under high pressure . Dry granulation is a powder agglomeration process used in the pharmaceutical industry to improve the flowability of powders by increasing the particle size. This operation is achieved using a roller press , which can have different configurations and equipment designs.

6. Steps involved in Dry Granulation Method Weighing formulation ingredients Mixing of formulation ingredients Compression of mixed powders into slugs Milling and sieving of slugs Mixing with disintegrant and lubricant Compression of granules into tablets

7. Step 1: Weighing formulation ingredients Here, appropriate quantities of formulation ingredients are dispensed. • · The excipients and the active ingredient must be in finely divided form, otherwise, particle size reduction should be carried out. Step 2: Mixing of formulation ingredients The dispensed formulation ingredients are mixed in a powder mixer until a uniform powder mix is achieved. It is worth noting that half amount of lubricant in the formula is added at this stage to enhance powder flow during slugging and to prevent sticking of compressed powder on the die during precompression. Step 3: Compression of mixed powders into slugs Here, the mixed ingredients are compressed into flat large tablets or pallets. This step is called precompression (slugging) and the compacts made in the process are termed slugs. Steps involved in Dry Granulation Method

8. Steps involved in dry granulation method Step 4: Milling and sieving of slugs Following slugging, the next stage in the manufacture of tablets by dry granulation usually involves breaking of slugs into smaller pieces using a hammer mill or other conventional milling equipment. The milled slugs are screened to produce uniform granules. Step 5: Mixing with disintegrant and lubricant After screening, the remaining lubricant and other extra granular excipients such as disintegrant, glidant etc. Are added to the granulation and mixed gently to achieve a uniform blend. Step 6: Compression of granules into tablets The mixed granules are compressed into tablets using either single or rotary tablet press fitted with appropriate punches and dies.

9. Advantages No need for water or solvents Ideal for moisture- and heat-sensitive drugs Simplifies the process (no drying step needed) More economical (less equipment and energy needed) Faster process compared to wet granulation Disadvantages Not suitable for all types of powders (especially low compressibility) Requires relatively high compaction forces Granules may be less uniform in size and density Tablets may have poor hardness and high friability Higher risk of powder segregation during processing

10. Wet granulation method Wet granulation is the process in which formation of granules is done by adding a granulating liquid . Here, a granulating fluid is used for the massing of powder particles . However, the fluid used here is essentially volatile and non-toxic . It should be volatile because only a volatile fluid can easily be removed by drying the final product. This method is used for the products not degraded by moisture and heat .

11. Excipents used for wet granulation Excipents used for wet granulation 1) Diluents/ fillers: to enhance bulk weight. E.g., Lactose, Manitol , Starch, DCP, Dextrose 2) Disintegrants: to breakdown tablets and granules. E.g., Sodium starch glycolate ( primojel ), Cross carmilose sodium (Ac Di sol), crosslinked PVP, Cellulose derivatives 3) Binders: for binding the powder particles E.g., (a) Natural – Gums, starch, cellulose, gelatin (b) Semisynthetic – Methyl cellulose, HPMC, HPC (c) Synthetic – Povidone ( PVP) 4) Glidents – Reduces inter particle friction and enhance flow. E.g., colloidal silicon dioxide ( Aerosil ) 5) Lubricants – reduce friction between grains and machine parts as well as prevent sticking Types- (a) Hydrophobic- e.g., Mg sterate (b) Hydrophilic – e.g., sodium steryl fumarate

12. Steps involved in wet granulation method Weighing and mixing of formulation ingredients Preparing the damp mass Wet screening/ Screening dampened powder into granules Drying of moist granules Sizing the granulation by dry screening Lubrication of granules Compression of granules into tablets

13. Steps involved in wet granulation Step 1: Weighing and mixing of formulation ingredients This step involves the weighing, sifting and introduction of specified quantities of drug substance(s), bulking agent, filler or diluent, and Disintegrants into a powder mixer. These ingredients are mixed using either a planetary bowl mixer, ribbon/ trough mixers, rotating drum mixer or high-speed mixer until a uniform powder mix is achieved. Excipents used for wet granulation Diluents/ fillers: to enhance bulk weight. E.g., Lactose, Manitol , Starch, DCP, Dextrose Disintegrants: to breakdown tablets and granules. E.g., Sodium starch glycolate ( primojel ), Cross carmilose sodium (Ac Di sol), crosslinked PVP, Cellulose derivatives

14. Steps involved in wet granulation Step 2: Preparing the damp mass Here, the binder solution is mixed with the powder mixture to form an adhesive mass which can be granulated. The amount of binding agent used as well as the quantity of fluid required to form a damp and coherent mass is part of the operator's skill. However, the resulting binder-powder mixture should compact when squeezed in the hand. Step 3: Wet screening/ Screening dampened powder into granules The wet massed powder blend is screened using 6 to 12 mesh screen to prepare wet granules. This may be done by hand or Mixing with suitable equipment that prepares granules by extrusion through perforations in the apparatus. The granules formed are spread evenly on trays & dried in an oven. Step 4: Drying of moist granules The screened moist granules are dried in an oven at a controlled temperature not exceeding 55°C to a consistent weight or constant moisture content. The drying temperature and duration of drying process depend on nature of active ingredient & level of moisture required for the successful production of satisfactory tablets.

15. Steps involved in wet granulation Step 5: Sizing the granulation by dry screening granule sizing The dried granules are passed through a screen of smaller size than the used to prepare the moist granules. The size of the final granules is dependent on the size of the punches (hence the final tablet Step 6: Lubrication of granules After dry screening, the dried and screened granules are separated into coarse and fine granules by shaking them on a 250 mesh sieve. Appropriate quantity of lubricant is passed through a 200-mesh sieve. This is mixed with the fine granules before the coarse granules are incorporated. Step 7: Compression of granules into tablets Here, the mixed granules are compressed in a single punch or multi station tablet press fitted with the appropriate punches and dies.

16. Advantages Improves flow properties of powders Enhances compressibility for better tablet formation Reduces dust generation Ensures uniform drug distribution Improves content uniformity of low-dose drugs Prevents segregation of drug and excipients Disadvantages Time-consuming process More expensive due to equipment and processing steps Not suitable for moisture-sensitive or thermolabile drugs Requires an additional drying step Batch-to-batch variability due to moisture and process conditions

17. Direct compression Direct Compression is a widely used method in tablet manufacturing where powders are compressed directly into tablets without the need for granulation (i.e., no wet or dry granulation step is involved). This method is fast, simple, and cost-effective, especially when the drug and excipients have good flowability and compressibility. When to use..
➤ For crystalline materials.
➤ For free flowing materials.
➤ For materials having good compressibility properties.
➤ For direct compression granular exceptients are preffered e.g Lactose S.D, Avicel pH 102,200 etc.

18. Advantages Fewer processing steps
Time and cost-efficient
No use of heat or water (ideal for heat/moisture-sensitive drugs)
Fewer stability issues
Scalable and easy to validate Disadvantages Poor content uniformity Requires excellent flowability and compressibility of materials
Risk of segregation during blending
Limited dose flexibility (not suitable for very low or very high drug doses) Dusting may be a problem in case of toxic drugs.

19. Equipments 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

20. 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. Oscillating Granulator works based on a mechanical granulation process.

21. Oscillating Granulator

22. 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. 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 degree angle. The rotating drum diameter is 60 to 350 milimeter . All the components of this machine adheres to GMP standards.

23. 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 . Confirms to Good Manufacturing Practice (GMP) standards.

24. 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 .

25. 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

26. Nauta Mixer Processor Nauta Mixers (also called Conical Screw Mixers) make use of a conical chamber with 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. Nauta Mixer Processor

28. 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.

29. Fluidized bed granulator

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