MICROMERITICSMICROMERITICS&&

PRECIPITATIONPRECIPITATION

Dr. Asra Hameed Dr. Asra Hameed Pharm.D (JUW) Pharm.D (JUW)

asra_hameed1@hotmail.casra_hameed1@hotmail.comom

CONTENTS:MICROMERITICS:

Definition & Origin of the term “MICROMERITICS”

ApplicationsFactors affecting the flow

properties of powdersParticle size analysis Particle size reduction Bulk densityTrue densityPorosityImportance of particle size

MICROMERITICS: Micromeritics is the science and

technology of small particles. The knowledge and control of the size of

particles is of importance in pharmacy. The size, and hence the surface area of a

particle, can be related to the physical, chemical & pharmacologic properties of drugs.

Clinically, the particle size of a drug can affect its release from dosage forms that are administered orally, parenterally, rectally & topically.

The successful formulation of suspensions, emulsions & tablets; both physical stability & pharmacologic response also depends on the particle size achieved in the product.

Origin:The term was created by. J. M. Dalla Valle in

his book MICROMERITICS THE TECHNOLOGY OF FINE PARTICLES.

It was derived from the Greek word for: small and part.

The size range which he covered in the book was from 10−1 to 105 micrometers.

Anything smaller than this but bigger than a molecule were referred to at the time as colloids but are now often referred to as nano particles..

Applications:Release & dissolutionParticle size & surface area influence the release

of a drug from a dosage form that is administered orally, rectally parenterally & topically. Higher surface area brings about intimate contact of the drug with the dissolution fluids in vivo & increases the drug solubility & dissolution.

Absorption & drug actionParticle size & surface area influence the drug

absorption & subsequently the therapeutic action. Higher the dissolution, faster the absorption & hence quicker & greater the drug action.

Applications:Physical stabilityMicromeritic properties of a particle i.e the

particle size in a formulation influences the physical stability of the suspensions & emulsions. Smaller the size of the particle, better the physical stability of the dosage form owing to the brownian movement of the particles in the dispersion.

Dose uniformityGood flow properties of granules & powders are

important in the manufacturing of tablets & capsules. The distribution of particles should be uniform in terms of number & weight.

Factors affecting the flow properties of powders:1.Particle’s Size and

Distribution 2.Particle Shape &

texture 3.Surface forces 4.Flow Activators

Particle’s size & Distribution:There is certain particle size at which

powder’s flow ability is optimum.Coarse particles are more preferred than fine

ones as they are less cohesive. The size distribution can also be altered to

improve flow ability by removing a proportion of the fine particle fraction or by increasing the proportion of coarser particles, such as occurs in granulation.

Particle Shape & texture:Particle’s Shape:

Generally, more spherical particles have better flow properties than more irregular particles. Spherical particles are obtained by spray drying, or by temperature cycling crystallization. - Flow activators are commonly referred as glidants.

- Flow activators improve the flow ability of powders

by reducing adhesion and cohesion. e.g. talc, maize starch and magnesium

stearat Particle's texture: particles with very rough surfaces will be

more cohesive and have a greater tendency to interlock than smooth surfaced particles.

Surface Forces:Reduction of electrostatic charges can

improve powder flow ability. Electrostatic charges can be reduced by altering process conditions to reduce frictional contacts.

Moisture content of particle greatly affects powder’s flow ability.

Adsorbed surface moisture films tend to increase bulk density and reduce porosity.

Drying the particles will reduce the cohesiveness and improve the flow.

Drying the particles will reduce the cohesiveness and improve the flow.

Flow activators:Flow activators are commonly referred

as glidants.Flow activators improve the flow ability

of powders by reducing adhesion and cohesion.

e.g. talc, maize starch and magnesium stearat

Methods for determining particle size:

1- Optical microscopy (range: 0.2 –100 um):

The microscope eyepiece is fitted with a micrometer by which the size of the particles may be estimated.

3.0 InstrumentationSeveral important features

are visible:Lenses Eyepieces (oculars)Light sourceCamera

Methods for determining particle size:

2- Sieving (range: 40-9500μm):

Standard sized sieves are available to cover a wide range of sizes. These sieves are designed to sit in a stack so that material falls through smaller and smaller meshes until it reaches a mesh which is too fine for it to pass through.

The stack of sieves is mechanically shaken to promote the passage of the solids.

The fraction of the material between pairs of sieve sizes is determined by weighing the residue on each sieve.

The result achieved will depend on the duration of the agitation and the manner of the agitation.

Methods for determining particle size:3-Sedimentation The tendency for particles in

suspension to settle out of the fluid in which they are entrained, and come to rest against a barrier.

It is the deposition or accumulation of sediment.

In this method large particles settle down rapidly while smaller particles take some time to settle down, so sedimented particles are taken out by the tube from the bottom and remaining are the fine particles.

Methods for determining particle size:4-ELUTRIATIONThe process of separating

the lighter particles from the heavier ones by means of an upward direction.

the process of elutriating is to purify, separate, or remove (ore, for example) by washing, decanting, and settling.

Size Reduction

Four commonly used methods for size reduction: Compression ImpactAttrition Cutting

Size reduction equipment Size reduction equipment is

divided into crushers, grinders, ultra fine grinders, and cutting machines

Crusher (coarse and fine, Jaw crushers etc) do the heavy work of breaking large pieces of solid material into small lumps.

Grinders(intermediate and fine, Attrition mills, Hammer mills, impactors) reduce crushed feed to powder. The product from an intermediate grinder might pass a 40-mesh screen; most of the product from a fine grinder would pass a 200-mesh screen with a 74mm opening.

Size reduction equipment An ultra fine grinder

(Fluid-energy mills, Hammer mills with internal classification etc) accepts feed particles no larger than 6mm and the product size is typically 1 to 5m m.

Cutters(Knife, cutters , dicers, slitters)give particles of definite size and shape, 2 to 10mm in length.

Bulk DensityBulk density is a property of

powders, granules and other “divided” solids, especially used in reference to mineral components (soil), chemical substances, (pharmaceutical) ingredients, foodstuff etc.

It is defined as the mass of particles of the material divided by the total volume they occupy.

Bulk density=mass/volume Bulk density=mass/volume as a wholeas a whole

The sum of the two gives the bulk volume:

Vb = Vgr + VpVb = Vgr + Vp

 True densityThe density of the

particles that makeup a powder or particulate solid, in contrast to bulk density, which measures the average density of a large volume of the powder in a specific medium (usually air).

It is defined as the mass of particles of the material divided by the true volume of particles.

True density=mass/real True density=mass/real volumevolume

Porosity Porosity is a measure of the

void spaces in a material, and is measured as a fraction, between 0–1, or as a percentage between 0–100%.

The porosity is defined as the ratio of the pore volume to the bulk volume, for example,

Importance of particle sizeBY SIZE REDUCTION;BY SIZE REDUCTION; Increase the surface area of drugs Easier & uniform mixing Rate of drying is enhanced Increase stability of emulsion Increase rate of adsorption Physical appearance improved

(ointments, paste & creams).Stability of some drugs increase in powder

form & decrease in solution formPowder drugs are easily administered than

solid dosage form.In suspension, cake form which quickly

redisperse upon shaking.

ContentsPrecipitation:Definition of the term

“PRECIPITATION”Process of precipitationPrecipitatePrecipitantSupernatant liquidApplications

PRECIPITATIONPrecipitation occurs through a

chemical reaction that forms an insoluble compound out of two or more soluble compounds.

Precipitation is the process of Precipitation is the process of separation of the solid separation of the solid substance from a solution:substance from a solution:

Either by altering the substance to an insoluble form,

Or by altering the solvent composition to lessen the solubility of the substance in it.

Process Of PrecipitationPrecipitation Reactions occur when

cations and anions of aqueous solutions combine to form an insoluble ionic solid, called a precipitate.

The most important method for precipitation is by displacement reaction taking place in the solution,

In which more active metal displace inactive or less active metal.

PrecipitateWhen the reaction occurs in a liquid, the solid formed is called the Precipitate.PrecipitantA substance that causes a

precipitate to form when it is added to a solution or suspension.

Supernatant liquidThe liquid remaining above the

solid is in either case called the supernate or supernatant.

Applications

It is used for:The separation of metal ions in aqueous

solutionThe analysis of metal ions in aqueous

solution The preparation of some of the substanceThe Purification of some of the substance

ApplicationsSeparationThe precipitate forms

because the solid (AgCl) is insoluble in

water.That is true for all

precipitates - the solids

are insoluble in aqueous solutions.

ApplicationsPreparationWhite lotion is prepared by

precipitationPurificationThe process of recrysallization is to

be done in purification.In which impure solid is absorb in the

suitable solvent at increased temperature.

After cooling, much of impurities remain absorbed in the solvent while the purified solid is precipitated.