partical size enlargement techniques

05/01/2023 Sagar Kishor Savale 1

Department of Pharmacy (Pharmaceutics) | Sagar savale

Particle Size Enlargement Techniques

Mr. Sagar Kishor Savale[Department of Pharmaceutics]

[email protected]

mailto:[email protected]


Contents

• DEFINATION• INTRODUCTION • FORCES• ADVANTAGES• DISADVANTAGE• METHOD OF PREPARATION• REFERENCE


INTRODUCTION• DEFINITION - Particle size enlargement is agglomeration of fine powder particle

to form uniform granule.

• Size- 0.5 to 2.0mm

• FORCE INVOLVED IN PARTICLE SIZE ENLARGEMENT

INTERMOLECULAR FORCES:

LONDON DISPERSION FORCES/ DISPERSION FORCES These forces are due to particle-particle adhesion, & exhibited when the

separations distance is less than 10-3 A0.


ELEECTROSTATIC FORCE:

It exist either as a result of interparticular friction or through the generation of opposite charge.

LIQUID & SOLID BRIDGES: Dispersing liquid into a powder mass will generally result in a

significant increase strength of particle-particle agglomerates.


METHOD OF PARTICLE SIZE ENLARGEMENT

• PELLITIZATION PROCESS 1. Powder Layering 2. Solution or Suspension Layering 3. Spray Drying & spray Congealing 4. Cryopelletization 5. Extrusion – Spheronization

• CRYSTALLIZATION

• GRANULLATION A) Wet Granulation B) Dry Granulation


ABOUT PELLETS

• Pellets are free flowing spherical units prepared from fine particle powder.

• Size- 0.5 to 1.5mm• For oral drug delivery/control drug delivery.• Coated pellets are administered in the form of

soft gelatin capsule or disintegrating tablet so that they remove to content in gastric environments.

• Shows their flexibility in different formulations.


PROPERTIES

• Excellent stability • Dust free round pallets• Good flow bahaviour• easy to dose • Compact structure• Low Hygroscopicity• High bulk density• Dense uniform surface• High active ingredient is possible• Controlled release application• Drug absorption can be alter• Risk of local damage to the mucosa reduced


ADVANTAGES

• Flexibility in the dosage form.• They can also blended to deliver incompatible

bioactive agent.• They may be given to provide different release

rate at different site of location.• Increases drug absorption and decrease

mucosal irritation.• They have excellent flow property .


DISADVANTAGES

• Size may vary formulation to formulation.• Capsule filling may increase cost and tabletting

may destroy the coating on pallet.


PELLETIZATION

• Conversion of powder particle to spherical particle.

• Size- 0.5-1.5 mm• Four method for pelletization –A. Powder layering B. Solution or suspension layering C. Spray drying/congealingD. Extrusion -spheronization


POWDER LAYERING


FLUIDIZED BED DRYER

1] Detachable chamber2] Fluidized bed3] Fluidized gas & liquid4] Blower5] Heater6] Filter7] Filter bag


FBD

• Principle- the bottom contain powder which we have to pelletized is placed in bowl.

Two nozzles are there (1)hot air (2)binding agent

Powder lifted from bottom and suspended in air the condition we called fluidized state.


WORKING•The powder to be pelletized are placed in a detachable bowl.• Then it is pushed into dryer fresh air is allowed to pass through filter which subsequently get heated into heater. •When the velocity of the air is greater than the settling velocity of the powder •the powder remain partially suspended in the gas stream, then the granule rise in the container because of high velocity of gas (3-8 m/s)•Fluidized state: the gas surrounding every forming pellets to complete them dry & uniform. the air leaves dryer by passing through the filter. Process is continued until desired size pellet is formed.


SOLUTION AND SUSPENSION LAYERING


WURSTER COATING PROCESS

• It is distinguishing feature from that of powder layering equipment cylindrical partition located in the product chamber and configuration of air to allow most of drying air to pass at high velocity around the nozzle and through the particle.


WURSTER PROCESSER


SPRAY DRYING/CONGEALINGThe spray dryer provides the large surface area for heat and mass transfer by automizing the liquid to small droplets. these are spread into a steam of hot air so that each droplet dries to individual solid particles. Thus the particle formation and drying occur in same process.


EXTRUSION-SPHERONIZATION• EXTRUDER : now a days three types of extruder present in

the market as follows: 1) Screw-fed extruder 2) Gravity-fed extrude 3) Ram-fed extruder


CRYOPELLETIZATION

• Process by which conversion of liquid droplets into the solid spherical particles by cooling with nitrogen.

• The pellets are dried in conventional freeze dryer to remove water and organic solvent.


CRYSTALLIZATION

• The spontaneous arrangements of repetitive orderly array.

• Process of crystallization as follows:


SOLUTION SUPERSATU--RATED SOL.

Diffusion &Deposition of

Particle on nuclei

COOLING OF EVAPORATION OF LOOSE SOLUTION SOLVENT AGGREGATES (SUPERSATURATE OR UNSATURATED) ADDITIVES ADDITION OF CRYSTAL OR CLUSTER BREAKING OF WEAK CRYSTAL

Embryo (LATTICE ARANGE MENT)

NUCLEI

CRYSTAL GROTH NUCLEATION

CRYSTALLIZATION


CRYSTALLIZATION INVOLVES THREE STEPS

1. Supersaturation 2. Nucleus formation3. Crystal growth


SUPERSATURATION

• Improve the solubility of the solvent by providing the energy with external factor such as

1. Evaporation of solvent2. Cooling of solution3. Addition of another substance


NUCLEATION

• Formation of small body or new phase in the solution which has become supersaturated before .

Crystal growth• The step is take place by diffusion process.• The solute molecule reach to the crystal and

lattice are formed.


Mire's theory

• Postulates a definite relationship between conc. And temp. at which crystal will spontaneously form in unseeded solution.

• According to it, the supersolubility curve represents the limit at which nucleus formation begins spontaneously and consequently the point were crystallization can start in the absence of any solid particle.


CON

C

TEMP.

G

F

DC

P

EB

A NORNAL SOLUBILITY CURVE

SUPERSOLUBILITY CURVE


Condition for mire's theory

• Solute and solvent must be pure• Solution must be free from solid solute

particle• Solution must be protected from entry of

particle• Soft or weak crystal must not form during

process• There should not fluctuation in temperature.


Limitations

• According to the theory, Crystallization starts at super solubility curve.

• If solution kept for longer period nucleation starts below solubilty curve.

• Miers theory applicable when,pure solute and solvent are used, which impossible.


Equipment used in crystallization:

•Agitated batch crystallizer •Swenson walker crystallizer•Krystal crystallizer•Vacuum crystallizer


GRANULATION

• Fine particles of powder are come together to form multiparticle entity.

• Size- 0.2-4.0 mm

Why granulation• To prevent the segregation of constituent of

powder mixture• To improve flow properties• To improve characteristics of mixture


Mechanism Of Granule Formation

1. Nucleation• granulation starts with particle-particle contact and adhesion due to

liquid bridge.• A no of particle joint to form pendular state, further agitation densities

the pendular bodies to form capillary state and bodies act as a nuclei for

further granule growth. 2. Transition

Nuclei can grow by two possible mechanism1. Either single particle can be added to the nuclei by pendular bridges.2. Two or more nuclei may be combine, the combine nuclei will be reshape

by agitation of bed


3. BALL GROWTHthe agitation is continued, granule coalescence will continue and produce unstable and over mass system . Although this is dependant upon liquid added and the particle of material being granule.


GRANULATION METHOD

1. Dry granulation• this require two places of equipment . A machine for

compressing dry powder into compacts and a mill for breaking of this intermediate product into granule.

• The dry granulation method can be used for drug that do not compress well after wet granulation or those which are sensitive to moisture.


WET GRANULATION

• In this, wet mass is forced through a sieve to produce wet granule

• Which are then dried.• A subsequent are used when water sensitive drug are

processed as an alternative to dry granulation or when a rapid drying is required (e.g. FBD)


REFERENCES

1. Michael e aulton. “pharmaceutics- the design and mfg of medicine”,3rd edition, Churchill Livingstone, p-p no. 410-422

2. Leon Lachman, Liberman A. “The Theory and Practice Of Industrial Pharmacy; varghese publishing house ; Third edition, P-P no. 317-324.

3. C. V. S. Subrahmanyan , “Pharmaceutical engineering” Vallabh Prakashan, P-P no.360-381.


Thank You

partical size enlargement techniques

Health & Medicine