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Size enlargement (Granulation)
Size Enlargement Granulation
The term “granulation” regularly refers to processes whereby aggregates with sizes ranging from about 0.1 to 2.0 mm are produced. The term “pelletization” is used synonymously with granulation, but in pharmacy this term is usually refers to the manufacture of aggregates, preferably spherical, with a narrow size distribution in the range of about 0.5 to 1.5 mm.
permanent aggregates in which the original particles can still be identified. .DEFINITION Granulation is a process of size enlargement whereby small particles are gathered into larger.
• To improve the appearance of the product • The granules being heavier do not blow out of the die and do not clog the lower punch . the mass uniformity of the dose. • To prevent segregation of ingredients in the mixture.reason for granulating powders • To improve the flow properties so that. • To reduce the environmental hazards for the working personnel due to dust formation from toxic materials. • To reduce the bulk volume of voluminous powders and make them more convenient for storage and transport. • To improve the compression characteristics of the mixture.
A compact or sheet is produced which is larger than the granule size required. . particle adhesion takes place because of applied pressure. (B) GRANULE GROWTH MECHANISMS In the dry methods. and the process is referred to as “slugging”. These bonds should be strong enough to allow granules to withstand handling without breakdown.Granulation mechanisms (A) PARTICLE-BONDING MECHANISMS During granulation. (3) The compact masses are called as slugs. and milling and sieving can attain therefore the required size. particles adhere and agglomerate due to bond formation.
Ball growth: • Further granule growth produces large. If agitation is continued. spherical granules and the mean particle size of the granulating system will increase with time. this point represents a suitable end point for granules used in capsule and tablet manufacture.Nucleation: • The granulation starts with adhesion among particles due to liquid bridges and the formation of agglomerates at capillary state. or two or more nuclei may combine. although this is dependent upon the amount of liquid added and the properties of the material being granulated. granule coalescence will continue and produce an unusable. 3. The combined nuclei will be reshaped by the agitation of the bed. 2. This stage is characterized by the presence of a large number of small granules with a fairly wide size distribution. If the size distribution is not excessively large. These structures may act as nucleus for successive enlargement of granules.Stages of granulation 1. Transition: • Nuclei can grow in two possible ways: either single particles can be added to the nuclei by bridges. . over massed system.
c) Abrasion transfer: • Agitation of the granule bed leads to the attrition of material from granules. forming a layer over the surface and increasing the granule size. d) Layering: • When a second batch of powder mix is added to a bed of granules the powder will adhere to the granules. This mechanism is only relevant to the production of layered granules using spheronizing equipment. forming a layer of material over the surviving granule. b) Coalescence: • Two or more granules join to form a larger granule. This abraded material adheres to other granules. increasing their size. .Mechanisms of ball growth a) Crushing and layering: • Granules break into fragments that adhere to other granules.
and this may be a major problem in pharmaceutical production.There is always some degree of overlap between these stages and it is very difficult to identify a given stage by inspection of the granulating system. . For end-product uniformity it is desirable to finish every batch of a formulation at the same stage.
Types of granulation .
3. Granulation by Crystallization. 2. this method is rarely used. This method exploits the presence of crystallization water in the active material. Wet granulation. .Methods of Granulation • Some of the available methods in the industrial field for the preparation of granules: 1. Dry Granulation.
These large tablets or sheets are milled. The high compression forces are obtained by using one of the following procedures: 1. Roller compaction: The powder mixture flow between two rollers to form a compressed sheet.Dry Granulation. Pharmaceutical powders that were mixed homogeneously together are compressed to obtain large tablets. . The milled sheets are sieved. Tabling machines 2.
.Wet Granulation • This is the most used method to prepare granules. • The main disadvantage of this method is the higher number of steps present in this process when compared with the other two methods.
Characteristics of the granulating liquid: It should have all required characteristics of pharmaceutical excipient. The 1st step is the wetting of the powder with a liquid or solution to form a paste. It should dissolve the powder only within a certain limit (mild solvent): If the powder is soluble in the solvent. . a solution or suspension will be obtained instead of the paste.Steps of Wet Granulation: 1.
• When two particles become in contact between each other by certain forces. . they institute: forces of electrostatic nature (week forces) & forces of viscous or/and adhesive natures (which are the most important) so the particles remain attached to each others. • Thus the used liquid in the wet granulation must be mild solvent for the powder.
• There is a few number of solvents available for pharmaceutical granulation. so if traces of the solvent remain in the formula at the end of the manufacturing. these traces must be non toxic for the patient. • . This is because we can’t totally eliminate the solvent.
3. the powder must be: fairly or discreetly soluble in the water compatible with it. 2. • If we want to use water for granulation. . Ethanol. Water. Isopropanol.• The most used solvents in wet granulation : 1.
Roller compaction granulator. Rotative granulator. Oscillating granulator. 3. High speed mixer granulator. . 6. Freund granulator. Fluidized bed granulator. 4. 5. 2.2. many granulators are available 1. To achieve this. The 2nd step is the granulation or the formation of granules starting from the paste.
Type of granulator.• The quality of the granules depends on the: 1. Powder nature. . 3. Granulation solvent. 2. which means that must remain aggregated & easily crumbled. • The paste that we have to obtain mustn’t drains between the fingers of the hand.
• we can measure the energy that we must provide to the system in which we carry out the wetting process. . Add gradually the granulating liquid. Put the powder for granulation in the granulator. Then mix by the use of electrical motor This motor measures the absorbed power in function of the time & so in function of the putted liquid. 2. 3. How? 1.
Granulation equipments .
Roller compactor ( Dry granulation) The powder mixture flow between two rollers to form a compressed sheet. . These large tablets or sheets are milled. The milled sheets are sieved.
These granules are poorly water-permeable due to the low porosity. low rate of dissolution due to the high compression force used to aggregate the powders. This will extremely reduce the velocity of dissolution & so the bioavailability of the active material.This system produces granules with: irregular shape. So. . water can’t permeate them easily in order to disintegrate & dissolve them.
dry granulation method is used only for those powders. which cannot be granulated with the wet granulation method ( when Drug is sensitive to heat or moisture or both. ) .
Diosna Mixer( Wet granulation) Gives more normal PSD with lesser fines. High shear mixer-granulator .
Fluid Bed Granulator-drier (wet granulation) .
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