Granulation ppt

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Aseminar on GRANULATION Presented by,Mr. NAMDEO SHINDE M. PHARM. (sem. I)Under the guidance of, Dr. N. H. ALOORKAR M.PHARM., Ph. D.11/8/20121SATARA COLLEGE OF PHARMACY, SATARA.

CONTENTSINTRODUCTION

METHODS OF GRANULATION

ADVANCED GRANULATION TECHNIQUES

CONCLUSION

REFERENCES

11/8/20122SATARA COLLEGE OF PHARMACY, SATARA.

IntroductionGranulesGranulationGranulation Technology


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Why we prepare granules when we have powders.?

11/8/2012SATARA COLLEGE OF PHARMACY, SATARA.4

11/8/2012SATARA COLLEGE OF PHARMACY, SATARA.5To 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.

To avoid powder segregation.

-Segregation may result in weight variation.

11/8/20126SATARA COLLEGE OF PHARMACY, SATARA.Contd...

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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)

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Dust free formulations. (Decrease dust generation and reduce employee exposure to drug product)

To eliminate poor content uniformity.


Methods of granulationDIRECT COMPRESSION

COMPRESSION GRANULATION

WET GRANULATION11/8/20129SATARA COLLEGE OF PHARMACY, SATARA.

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


Steps in Dry Granulation


How can we do it?11/8/201212SATARA COLLEGE OF PHARMACY, SATARA.Contd

By two waysSLUGGINGROLLER COMPACTIONLarge tablet produced in heavy duty tablet press. Powder is squeezed between two rollers to produce sheet of material e.g. Chilsonator11/8/201213SATARA COLLEGE OF PHARMACY, SATARA.Contd

EquipmentsHas two parts,Machine for compressing dry powder to form compacts.

Mill for breaking these intermediates to granule.

e.g. CHILSONATER HAMMER MILL11/8/201214SATARA COLLEGE OF PHARMACY, SATARA.Contd


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COMPRESSION granulationIt mainly involves three steps -

Milling of drug and excipients Mixing of drug and excipients

Tablet compression


11/8/201217SATARA COLLEGE OF PHARMACY, SATARA.Contd

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wet granulationIn this, powdered medicament and other excipients are moistened with granulating agent. 11/8/201218SATARA COLLEGE OF PHARMACY, SATARA.

Steps in wet granulation11/8/201219SATARA COLLEGE OF PHARMACY, SATARA.Contd




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MethodsSingle pot granulation

High shear mixture granulation

Fluid bed granulation

Extrusion- Spheronization


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


Single pot granulator


High shear mixture granulation


11/8/2012SATARA COLLEGE OF PHARMACY, SATARA.27Rapid mixer granulator

ADVANTAGESDISADVANTAGESShort 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.

11/8/201228SATARA COLLEGE OF PHARMACY, SATARA.Contd..

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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.


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-Homogeneous granules.

---Gentle product handling.

--Uniform spraying of all particles in the fluid bed.


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Advantages

1.It reduces dust formation during processing

2. It reduces product loss

3. It improves worker safety.

Disadvantages

The Fluid Bed cleaning is labor-intensive and time consuming.

2. Difficulty of assuring reproducibility.


Extrusion-Spheronization1.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


Extrusion-Spheronization

Different steps involved in the Extrusion- Spheronization process11/8/201233SATARA COLLEGE OF PHARMACY, SATARA.

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)


Freeze granulation Technology

Steam Granulation

Melt Extrusion Technology

Liquisolid Technique

TOPO Technology

Continuous Flow Technology


This process is a modification of conventional wet granulation.

Here steam is used as a binder instead of water.Steam Granulation11/8/201236SATARA COLLEGE OF PHARMACY, SATARA.

Advantages1.Uniformly distribution the powder particles.

2. Higher dissolution rate of granules because of larger surface area generated.

3. Time efficient.

4. Maintain sterility.


DisadvantagesRequires special equipment for steam generation and transportation.

2. Requires high energy inputs.

3. Thermolabile materials are poor candidates.

4. More safety measure required.


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 80C.

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.Melt Granulation 11/8/201239SATARA COLLEGE OF PHARMACY, SATARA.

e.g. Polyethylene Glycol (PEG)2000, 4000, 6000, 8000 (40-60 0C) water soluble binders- water insoluble binders- e.g.. Stearic acid (46-59 0C),Cetyl or stearyl alcohol(56-60 0C)



MOISTURE ACTIVATED DRY GRANULATIONIn MADG, moisture is used to activate granule formation, without the need to apply heat to dry the granules.

-Drug is blended with diluents and powder-A small amount of water (1-4%) Is sprayed -Agglomerate formation (size 150500m)STAGESAGGLOMERATIONMOISTURE DISTRIBUTION/ ABSORPTION

-Moisture absorbents like microcrystalline cellulose or silicon dioxide, are added while mixing.

-Moisture redistribution within the mixture.

Entire mixture becomes relatively dry.11/8/201242SATARA COLLEGE OF PHARMACY, SATARA.

Advantages:

Applicable to more than 90% of the granulation need for pharmaceutical, food and nutritional industry.2. Time efficient.3. Suitable for continuous processing4. Less energy involved during processing.

Disadvantages:

Moisture sensitive and high moisture absorbing API are poor candidates.11/8/201243SATARA COLLEGE OF PHARMACY, SATARA.Contd

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.

Moist Granulation Technique (MGT) 11/8/201244SATARA COLLEGE OF PHARMACY, SATARA.

Thermal Adhesion Granulation Process (TAGP)-It is applicable for preparing direct tableting formulations.

-Mixture of API and excipients are heated to a temp. 30-130C . in closed system until granulation.

It provides granules with-

- Good flow properties. - Binding capacity to form tablets of low friability. - Adequate hardness.



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.11/8/201247SATARA COLLEGE OF PHARMACY, SATARA.


TOPO TechnologyHERMES 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.11/8/201249SATARA COLLEGE OF PHARMACY, SATARA.

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.

11/8/201250SATARA COLLEGE OF PHARMACY, SATARA.Continuous Flow Technology

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.


11/8/2012SATARA COLLEGE OF PHARMACY, SATARA.52Sr. No.ParametersMethod1Particle MorphologyOptical microscopy2Particle Size DistributionSieve analysis, laser light scattering3NaturePowder X-Ray Diffraction4Surface AreaGas adsorption5Granule PorosityMercury intrusion methods6Granule StrengthDevelopment of a Formulation7Granule Flowability and DensityHopper Method, Density Apparatus

Granulation Characterization:

11/8/2012SATARA COLLEGE OF PHARMACY, SATARA.53CONCLUSION


6th INTERNATIONAL GRANULATION CONFERENCE At Sheffield, UK. Dates of Event- 26th June 2013 - 28th June 2013.

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REFERENCES11/8/2012SATARA COLLEGE OF PHARMACY, SATARA.551) 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).

THANK YOU.11/8/2012SATARA COLLEGE OF PHARMACY, SATARA.56

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Granulation ppt