1. GRANULATION DR. MOHAMMAD KHALID ANWER Assistant Professor 2/25/20161 COLLEGE OF PHARMACY, PRINCE SATTAM BIN ABDULAZIZ UNIVERSITY

2. CONTENTSCONTENTS INTRODUCTION METHODS OF GRANULATION ADVANCED GRANULATION TECHNIQUES CONCLUSION 2

3. Introduction GGGGranules GGGGranulation GGGGranulation Technology 3

4. Why we prepare when we have powders….? Why we prepare granules when we have powders….? 4

5. 5  To  To avoid powder segregation. enhance the flow of powder. produce uniform mixtures. produce dust free formulations. eliminate poor content uniformity. improve compaction characteristics of mix.

6.  To avoid powder segregation. -Segregation may result in weight variation -Segregation may result in weight variation. 2/25/20166 SATARA COLLEGE OF PHARMACY, SATARA. Contd...

7.  To enhance the flow of powders. (Higher flowability gives better filling of the dies or containers)  To produce uniform mixtures. (Mixtures of various particles tend to segregate in transport or handling because of differences in particle size, shape and density) 7 Contd...

8.  Dust free formulations. (Decrease dust generation and reduce employee exposure to drug product)  To eliminate poor content uniformity. 8

9. Methods of granulation DDDDIRECT COMPRESSION CCCCOMPRESSION GRANULATION WWWWET GRANULATION 9

10. When To Choose DRY method? Drug Drug dose is too high. Do Do not compress well after wet granulation. Heat Heat sensitive drugs. Moisture Moisture sensitive drugs. e.g. Aspirin, Vitamins 10

11. Steps in Dry Granulation Compaction of powder Milling Screening 11

12. How can we do it………? we do it………? 12 Contd…

13. By two ways SLUGGING ROLLER COMPACTION Large tablet produced in heavy duty tablet in heavy duty tablet press. press. Powder is squeezed between two rollers to produce sheet of material e.g. Chilsonator 13 Contd…

14. Equipments Has two parts,  Machine  Machine for compressing dry powder to form compacts.  Mill  Mill for breaking these intermediates to granule. e.g. e.g. CHILSONATER HAMMER MILL 14 Contd…

15. COMPRESSION granulation It mainly involves three steps -  Milling  Milling of drug and excipients  Mixing  Mixing of drug and excipients  Tablet  Tablet compression 15

16. Disadvantages CAPPING EQUIPMENTS ARE EXPENSIVE LAMINATION 16 Contd…

17. wet granulation In this, powdered medicament and other excipients are moistened with granulating agent. 17

18. Steps in wet granulation 1 Mixing of the drug(s) and excipients 2 Mixing of binder solution with powder mix. to form wet mass 3 Coarse screening of wet mass using a suitable sieve. (6-12 # screens) 4 Drying of moist granules. 5 Screening of dry granules through a suitable sieve (14-20 # screen). 18 Contd…

19. Granulating liquid - Volatile -Non-toxic -Non-toxic e.g. Water, Ethanol, Isopropanol Binding agent- Natural Polymers Natural Polymers: Starch, Pregelatinized Starch synthetic binders: PVP, MC, HPMC, Maltrodextrins 19 Contd…

20. Limitation of wet granulation TIME EQUIPMENTS LOSS OF MATERIAL SPACE ENERGYLABOR 20 Contd…

21. Methods  Single pot granulation  High shear mixture granulation  Fluid bed granulation  Extrusion- Spheronization 2/25/201621 Contd…

22.  Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment. e.g. Single Pot Processor / One-Pot Processor 2/25/201622

23. Single pot granulator 2/25/201623

24.  High shear mixture granulation Dry Powder mixing (Approx 2-5 mins ) Liquid binder addition (Approx 1-2 mins)Wet massingWet sieving of granulesDryingDry sieving of granules 2/25/201624

25. 2/25/201625 Rapid mixer granulator

26. ADVANTAGESADVANTAGES DISADVANTAGESDISADVANTAGES  Short processing time.  Lesser amount of liquid binders required compared with FBG.  Highly cohesive material can be granulated.  Increase in temperature may cause chemical degradation of thermolabile material.  Over wetting of granules can lead to large size lumps formation. 2/25/201626 Contd..

27.  Fluid bed granulation Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a air/gas. Granulating and drying can be completed in one step inside the machine. 2/25/201627

28. -Homogeneous granules. -- -Gentle product handling. -- Uniform spraying of all particles in the fluid bed. 2/25/201628 Contd…

29. Advantages 1.It reduces dust formation during processing 2. It reduces product loss 3. It improves worker safety. Disadvantages 1.The Fluid Bed cleaning is labor-intensive and time consuming. 2. Difficulty of assuring reproducibility. 2/25/201629 Contd…

30.  Extrusion-Spheronization 1.Dry mixing of materials to achieve homogeneous dispersion. 2. Wet granulation of the resulted mixture to form wet mass. 3. Extrusion of wet mass to form rod shaped particles. 4. Rounding off (in spheronizer) 5. Drying 2/25/201630

31. Extrusion-Spheronization Different steps involved in the Extrusion- Spheronization process 2/25/201631

32. Advanced Granulation Techniques  Steam Granulation  Melt Granulation  Moisture Activated Dry Granulation (MADG)  Moist Granulation Technique (MGT)  Thermal Adhesion Granulation Process (TAGP)  Foam Granulation  Pneumatic Dry Granulation (PDG) 2/25/201632

33.  Freeze granulation Technology  Steam Granulation  Melt Extrusion Technology  Liquisolid Technique  TOPO Technology  Continuous Flow Technology 2/25/201633 Contd…

34. 2/25/201634 Sr. No.ParametersMethod 1Particle MorphologyOptical microscopy 2Particle Size DistributionSieve analysis, laser light scattering 3NaturePowder X-Ray Diffraction 4Surface AreaGas adsorption 5Granule PorosityMercury intrusion methods 6Granule StrengthDevelopment of a Formulation 7Granule Flowability and DensityHopper Method, Density Apparatus G RANULATION C HARACTERIZATION :