Particle size enlargement methods:

. Granulation is the process of collecting particles together by creating bonds between them. Why enlarge particle size: • To prevent segregation of the constituents of the powder mix. • To produce dust free formulation.g. tabletting). • sintering.(agglomeration by agitation) • Compaction (e. • To capture and fuse small quantities of active material. • Extrusion. • To eliminate poor content uniformity.• Granulation. • spray drying and • prilling. • To produce uniform mixtures. Bonds are formed by compression or by using a binding agent. • To improve the compaction characteristics of the Mix. • To control density.

Roller compaction .

iv) Coarse screening of wet mass using a suitable sieve (6-12 # screens). vi) Screening of dry granules through a suitable sieve (14-20 # screen). TUMBLING GRANUALATOR (1-20mm granules) 1. as growth by coalescence of the seed particles is hard to control. ● Tumbling equipment is also suitable for coating large particles. A key advantage to these systems is the ability to run at large scale. . DRUM GRANUALATOR ● Granule density generally falls between that of fluidized-bed and mixer granulators and it is difficult to produce highly porous agglomerates in tumbling granulators. ● Drums with diameters up to four meters and throughputs up to 100 ton/hr are widely used in the mineral industry. but it is difficult to coat small particles.WET GRANUALATION Important steps involved in the wet granulation i) Mixing of the powder and excipients ii) Preparation of binder solution iii) Mixing of binder solution with powder mixture to form wet mass. v) Drying of moist granules. ● Drum and disc granulators generally operate in continuous feed mode. DISC GRANUALATOR 2.

MIXER GRANUALATOR (<2 mm) high-density granules. and are generally denser due to higher-agitation intensity . sticky materials.. ● Less amount of liquid binder required as compared to fluidized bed ● They are less sensitive to operating conditions than tumbling granulators.) ● They can process plastic. ● They can spread viscous binders. ● Granules produced in mixer granulators may not be as spherical as those produced in tumbling granulators.

● Granules obtained are more porous than those obtained from shear mixers. ● Disadvantages include the effect of high operating costs with respect to air handling and dust containment.FLUIDIZED BED GRANUALATOR ● Fluidized granulators produce either high-porosity granules due to the agglomeration of powder feeds or high-strength layered granules due to coating of seed particles or granules by liquid feeds. high heat and mass-transfer rates. and the potential of defluidization due to uncontrolled growth. Reduce dust formation . ● Advantages of fluidized-beds over other granulation systems include high-volumetric intensity. ● Reduce product loss. simultaneous drying and granulation.

Here steam is used as a binder instead of water. have large surfacearea hence increased dissolution rate of the drug from granules. But this method is not suitable for thermolabile substances. When water soluble binders are needed. lowers dissolution rate so can be used for preparation of taste masked granules without modifying availability of the drug. . Its severalbenefits includes higher distribution uniformity. amount of liquid binder can be controlled precisely and the production and equipment costs are reduced. But the limitation is that it is unsuitable for thermolabile drugs. Melted binder then acts like a binding liquid. freshly distilled steam is sterile and therefore the total count can be kept under control. no health hazards to operators. di-. Stearic acid. various waxes and mono-. ● Melt Granulation / Thermoplastic Granulation Here granulation is achieved by the addition of meltable binder. & triglycerides re used as melting binders. no restriction by ICH on traces left in the granules. Moreover special equipments are required and are unsuitable for binders that cannot be later activated by contact with water vapour. Moreover. There is no need of drying phase since dried granules are obtained by cooling it to room temperature. steam granules are more spherical. higher diffusion rate into powders. morefavourable thermal balance during drying step. When water insoluble binders are needed. compared to the use of organic solvent water vapour is environmentally friendly. cetyl or stearyl alcohol. It is useful for granulating water sensitive material and producing SR granulation or solid dispersion. processing time is shorter therefore more number of tablets are produced per batch. Advancement in Granulations ● Steam Granulation It is modification of wet granulation.Extrusion-spheronization i) Ability to incorporate higher levels of active components without producing excessively larger particles. That is binder is in solid state at room temperature but melts in the temperature range of 50 – 80˚C. ii) Applicable to both immediate and controlled release dosage form. Polyethylene Glycol (PEG) is used as melting binders.

no overwetting. It decreases drying time and produces granules with excellent flowability. It provides granules with good flow properties and binding capacity to form tablets of low friability. TAGP is performed under low moisture content or low content of pharmaceutically acceptable solvent by subjecting a mixture containing excipients to heating at a temperature in the range from about 30ºC to about 130ºC in a closed system under mixing by tumble rotation until the formation of granules. It has several benefits over spray(wet) granulation such as it requires less binder than Spray Granulation. This method utilizes less water or solvent than traditional wet granulation method. reduce manufacturing time. useful for granulating water sensitive formulations. This method utilizes very little granulating fluid. or invitro drug dissolution properties. ● Foam Granulation Here liquid binders are added as aqueous foam. no plugging problems since use of spray nozzles is eliminated. ● Moist Granulation Technique (MGT) A small amount granulating fluid is added to activate dry binder and to facilitate agglomeration. It is applicable for developing a controlled release formulation. uniform distribution of binder throughout the powder bed. no detrimental effects on granulate. Then a moisture absorbing material like Microcrystalline Cellulose (MCC) is added to absorb any excess moisture. Tablets prepared using MADG method has better content uniformity. less binder required for Immediate Release (IR) and Controlled Release (CR) formulations. tablet. By adding MCC in this way drying step is not necessary. . ● ThermalAdhesion Granulation Process (TAGP) It is applicable for preparing direct tableting formulations. adequate hardness and have a high uptake capacity for active substances whose tableting is poor. reduces drying time. rate of addition of foam is greater than rate of addition of sprayed liquids. requires less water to wet granulate.● Moisture Activated Dry Granulation (MADG) It involves moisture distribution and agglomeration.