Granulation ppt.
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The document discusses various granulation techniques used in pharmaceutical manufacturing. It begins with an introduction to granules and granulation. It then covers different granulation methods including dry granulation, wet granulation and advanced techniques like fluid bed granulation, extrusion-spheronization, steam granulation and melt granulation. The document provides details on the process, equipment used, advantages and disadvantages of each method. It aims to explain why granulation is important and the various ways it can be achieved.
Granulation ppt.
- 1. A seminar on GRANULATION Presented by, Under the guidance of, Mr. NAMDEO SHINDE Dr. N. H. ALOORKAR M. PHARM. (sem. I) M.PHARM., Ph. D. SATARA COLLEGE OF PHARMACY, SATARA. 1/27/2013 1
- 2. CONTENTS INTRODUCTION METHODS OF GRANULATION ADVANCED GRANULATION TECHNIQUES CONCLUSION REFERENCES 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 2
- 3. Introduction Granules Granulation Granulation Technology 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 3
- 4. Why we prepare granules when we have powders….? 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 4
- 5. To avoid powder segregation. To enhance the flow of powder. To produce uniform mixtures. To produce dust free formulations. To eliminate poor content uniformity. To improve compaction characteristics of mix. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 5
- 6. To avoid powder segregation. Contd... -Segregation may result in weight variation. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 6
- 7. Contd... 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) SATARA COLLEGE OF PHARMACY, SATARA. 1/27/2013 7
- 8. Dust free formulations. (Decrease dust generation and reduce employee exposure to drug product) To eliminate poor content uniformity. SATARA COLLEGE OF PHARMACY, SATARA. 1/27/2013 8
- 9. Methods of granulation DIRECT COMPRESSION COMPRESSION GRANULATION WET GRANULATION SATARA COLLEGE OF PHARMACY, SATARA. 1/27/2013 9
- 10. When To Choose DRY method? Drug dose is too high. Do not compress well after wet granulation. Heat sensitive drugs. Moisture sensitive drugs. e.g. Aspirin , Vitamins SATARA COLLEGE OF PHARMACY, SATARA. 1/27/2013 10
- 11. Steps in Dry Granulation Compaction of powder Milling Screening 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 11
- 12. Contd… How can we do it………? 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 12
- 13. Contd… By two ways ROLLER SLUGGING COMPACTION Large tablet produced Powder is squeezed in heavy duty tablet between two rollers to press. produce sheet of material e.g. Chilsonator 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 13
- 14. Contd… Equipments Has two parts, Machine for compressing dry powder to form compacts. Mill for breaking these intermediates to granule. e.g. CHILSONATER HAMMER MILL 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 14
- 15. Advantages Disadvantages Less No uniform equipments & color space distribution Eliminate Process create need of binder more dust solution 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 15
- 16. COMPRESSION granulation It mainly involves three steps - Milling of drug and excipients Mixing of drug and excipients Tablet compression 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 16
- 17. Contd… CAPPING LAMINATION EQUIPMENTS ARE EXPENSIVE 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 17
- 18. wet granulation In this, powdered medicament and other excipients are moistened with granulating agent. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 18
- 19. Contd… Steps in wet granulation • Mixing of the drug(s) and excipients 1 • Mixing of binder solution with powder mix. to form 2 wet mass • Coarse screening of wet mass using a suitable sieve . 3 (6-12 # screens) 4 • Drying of moist granules. • Screening of dry granules through a suitable sieve 5 (14-20 # screen). 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 19
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- 21. Contd… Granulating Binding liquid agent- Natural Polymers: -Volatile Starch, -Non-toxic Pregelatinized Starch e.g. synthetic binders: PVP, MC, HPMC, Water, Ethanol , Isopropanol Maltrodextrins 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 21
- 22. Contd… TIME LABOR EQUIPMENTS Limitation of wet granulation LOSS OF ENERGY MATERIAL SPACE 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 22
- 23. Methods Contd… Single pot granulation High shear mixture granulation Fluid bed granulation Extrusion- Spheronization 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 23
- 24. 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 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 24
- 25. Single pot granulator 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 25
- 26. High shear mixture granulation Dry Powder mixing (Approx 2-5 mins) Liquid binder addition (Approx 1-2 mins) Wet massing Wet sieving of granules Drying Dry sieving of granules 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 26
- 27. Rapid mixer granulator 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 27
- 28. Contd.. ADVANTAGES DISADVANTAGES Increase in Short processing time. temperature may cause chemical degradation of Lesser amount of liquid thermolabile material. binders required compared with FBG. Over wetting of granules can lead to large Highly cohesive material size lumps formation. can be granulated. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 28
- 29. Fluid bed granulation Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas. Granulating and drying can be completed in one step inside the machine. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 29
- 30. Contd… -Homogeneous granules. ---Gentle product handling. --Uniform spraying of all particles in the fluid bed. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 30
- 31. Contd… Advantages Disadvantages 1.It reduces dust 1. The Fluid Bed cleaning is formation during labor-intensive and time processing consuming. 2. It reduces product loss 2. Difficulty of assuring 3. It improves worker reproducibility. safety. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 31
- 32. 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 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 32
- 33. Extrusion-Spheronization Different steps involved in the Extrusion- Spheronization process 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 33
- 34. 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) 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 34
- 35. Contd… Freeze granulation Technology Steam Granulation Melt Extrusion Technology Liquisolid Technique TOPO Technology Continuous Flow Technology 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 35
- 36. Steam Granulation This process is a modification of conventional wet granulation. Here steam is used as a binder instead of water. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 36
- 37. Contd… Advantages 1.Uniformly distribution the powder particles. 2. Higher dissolution rate of granules because of larger surface area generated. 3. Time efficient. 4. Maintain sterility. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 37
- 38. Contd… Disadvantages 1. Requires special equipment for steam generation and transportation. 2. Requires high energy inputs. 3. Thermolabile materials are poor candidates. 4. More safety measure required. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 38
- 39. Melt Granulation Here granulation is achieved by the addition of meltable binder. Binder is in solid state at room temperature but melts in the temperature range of 50 – 80˚C. Melted binder then acts like a binding liquid. There is no need of drying phase since dried granules are obtained by cooling it to room temperature. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 39
- 40. Contd… water soluble binders- e.g. Polyethylene Glycol (PEG) 2000, 4000, 6000, 8000 (40-60 0C) water insoluble binders- e.g.. Stearic acid (46-59 0C), Cetyl or stearyl alcohol(56-60 0C) 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 40
- 41. Contd… Advantages Disadvantages -Heat sensitive materials are -Time and cost effective poor candidates - Lower-melting-point binder -Controlling and may melt/ soften during modifying the release of handling and storage drugs -Higher-melting-point binders require high melting temp. -Water sensitive drugs are and can contribute instability good candidates problems for heat-labile materials. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 41
- 42. MOISTURE ACTIVATED DRY GRANULATION In MADG, moisture is used to activate granule formation, without the need to apply heat to dry the granules. STAGES MOISTURE DISTRIBUTION/ AGGLOMERATION ABSORPTION -Moisture absorbents like -Drug is blended with diluents microcrystalline cellulose or and powder silicon dioxide, are added while mixing. -A small amount of water (1-4%) Is sprayed -Moisture redistribution within the mixture. -Agglomerate formation (size 150–500μm) Entire mixture becomes relatively dry. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 42
- 43. Contd… Advantages: 1.Applicable to more than 90% of the granulation need for pharmaceutical, food and nutritional industry. 2. Time efficient. 3. Suitable for continuous processing 4. Less energy involved during processing. Disadvantages: 1. Moisture sensitive and high moisture absorbing API are poor candidates. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 43
- 44. Moist Granulation Technique (MGT) A small amount granulating fluid is added to activate dry binder and to facilitate agglomeration. Moisture absorbing material like Microcrystalline Cellulose (MCC) is added to absorb any excess moisture. Drying step is not necessary. Applicable for developing a controlled release formulation. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 44
- 45. Thermal Adhesion Granulation Process (TAGP) -It is applicable for preparing direct tableting formulations. -Mixture of API and excipients are heated to a temp. 30-130ºC . in closed system until granulation. It provides granules with- - Good flow properties. - Binding capacity to form tablets of low friability. - Adequate hardness. 1/27/2013 SATARA COLLEGE OF 45 PHARMACY, SATARA.
- 46. TIME EFFICIENT COST NO EFFECTIVE OVERWETTING FOAM GRANULATION IR, CR UNIFORM FORMULATION BINDER DISTRIBUTION WATER SENSITIVE DRUGS 1/27/2013 SATARA COLLEGE OF 46 PHARMACY, SATARA.
- 47. Freeze granulation Technology Developed and adopted by , Swedish Ceramic Institute (SCI). -By spraying a powder suspension into liquid nitrogen, the drops (granules) are instantaneously frozen. In a subsequent freeze- drying the granules are dried by sublimation of the ice without any segregation effects. -Finally it produces spherical, free flowing granules. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 47
- 48. Contd… 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 48
- 49. TOPO Technology HERMES PHARMA has developed unique technology for carrying out single pot granulation. Requires very small quantity of liquid to start the chain reaction Pure water or water-ethanol mixtures are used. Technology produces granules for tablets which contain at least one solid crystalline, organic acid and one alkaline or alkaline earth metal carbonate that reacts with the organic acid in aqueous solution to form carbon dioxide. As a result, there are no solvent residues in the finished products, granules have excellent hardness and stability. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 49
- 50. Continuous Flow Technology The technology does not need any liquid to start the chain reaction. Granulation is carried out in an inclined drum into which powder is fed at one end and granulate is removed at the other. The process produces granule with surface protected by inactive component that do not harm to sensitive API. CF technology can produce up to 12 tons of granules every day. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 50
- 51. Contd… Key Benefits- Sensitive APIs are protected . Granules and effervescents become less sensitive to humidity and high temperature. Granules form extremely stable products. No solvent residues in the final products. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 51
- 52. GRANULATION CHARACTERIZATION: Sr. No. Parameters Method 1 Particle Morphology Optical microscopy 2 Particle Size Distribution Sieve analysis, laser light scattering 3 Nature Powder X-Ray Diffraction 4 Surface Area Gas adsorption 5 Granule Porosity Mercury intrusion methods 6 Granule Strength Development of a Formulation 7 Granule Flowability and Density Hopper Method, Density Apparatus 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 52
- 53. CONCLUSION SATARA COLLEGE OF PHARMACY,
- 54. 6th INTERNATIONAL GRANULATION CONFERENCE At Sheffield, UK. Dates of Event- 26th June 2013 - 28th June 2013. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 54
- 55. REFERENCES 1) Stahl H, A review article on latest process advancements and innovations in Granulation technology. 2) Yadav V. B., Yadav A. V., Liquisolid granulation technique for tablet manufacturing: an overview in Journal of Pharmacy Research. 3)Malcolm Summers, Michael Aulton, a review on Granulation. 4) Niro pharma system on current issues and troubleshooting fluid bed granulation,may1998. 5)Harald Stahl,Senior pharmaceutical technologist, GEA Pharma Systems, Germany 7)Detlev Haack . Hermes Arzneimittel GmbH – Division Hermes Pharma, Grosshesselohe (Germany). 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 55
- 56. THANK YOU…. 1/27/2013 SATARA COLLEGE OF PHARMACY, SATARA. 56