Micro Me Retics

Md. Asif Hasan NiloYPharmacy 3rd Semester (24 Batch)

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MicromeriticsThe term micromeritics means the science and technology of small particles.

Importance in PharmacyThe study of particle size and particle size distribution has a number of applications

in the field of Pharmacy including the following: -

1. The physical properties of powders such as bulk density, porosity,compressibility are dependent on the particle size and size distribution. Forexample, the bulk density of light and heavy magnesium carbonate differs dueto particle size difference.

2. The flow properties of powders dependent upon the particle size, sizedistribution as well as the particle shape. Asymmetric particles have very poorflow characteristics hence granulation techniques are used to convert blends ofdrugs.

3. Properties of drugs such as rate of absorption and hence pharmacologicalactivity depend on the particle size.

4. Elegance of pharmaceutical preparations such as emulsions, suspensions,ointments often depend upon the particle size of the dispersed phase.

5. The release characteristics of drugs from ointments, creams and suppositories aredependent on the particle size of the dispersed drug.

6. The chemical properties of drugs such as surface oxidation also depend on theparticle size.

Phase size and size distributionIn a collection of particles more than one size, two properties are important,

which are:-i. The shape and surface area of the individual particles.ii. The size range and weight or number of particles present and total surface area.

The size of a sphere is readily expressed in terms of diameter. Various types ofdiameter are discussed in micromeritics.

Equivalent Spherical Diameter: It relates the size of the particles to the diameterof the sphere having the same surface area, volume or diameter.

Volume diameter: It is the diameter of a sphere having the same volume. Surface Diameter: it is the diameter of a sphere having the same surface area. Projected Diameter: it is the diameter of a sphere having the same observed

area as the particle when viewed normal to its most stable plane. Stokes Diameter: it describes an equivalent sphere undergoing sedimentation at

the same rate as the asymmetric particle.

Methods for Determining Particle SizeThere are four available methods for determining particle size. They are: -


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1. Optical microscopy.2. Sieving.3. Sedimentation.4. Particle Volume Measurement.

Optical Microscopy (fig)Principle:

It should be possible to use ordinary microscope for the measurement of particlesize range 0.2 μm to about 100 μm. According to the microscopic method, anemulsion or suspension, diluted or undiluted, is mound or a slide or placed on amechanical stage. The microscopic eyepiece is fitted with a micrometer by whichthe size of the particle may be estimated. The field can be projected on a screenwhere the particles are measured more easily.

Size Range: 0.2 μm to about 100 μm.

Method:The particles are measured along by chosen fixed line, generally made

horizontally across the center of the particle. Popular measurement is: -i. Feret diameter.ii. Martin diameter.iii. Projected area diameter.

Advantage:Presence of agglomerates and particles of more than one component may often

be detected.

Disadvantages:1. Diameter is obtained from only two dimensions of the particles; length &

breadth.2. No emission of the depth of the particle is not ordinary available.3. Slow and tedious.

Application:Determination of particle size of microscopy crystalline cellulose, sodium

carbonyl methyl cellulose, sodium starch glycolate & Methyl cellulose.


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SIEVINGPrinciple:

Sieving, in which particles are passed by mechanical shaking through a series ofsieves of known and successively smaller size and the determination of proportionof powder passing through each sieve (range 40 to 9500 μm) depending uponsieve size. Sieves are produce by photo etching and electroforming techniques.Powders of vegetable and animal drugs are officially defined as follows: -

Very coarse powder (No.8): All particles pass through a No.8 sieve and notmore than 20% through a No.60 sieve.

Coarse powder (No.20): All particles pass through a No.20 sieve and not morethan 40% through a No.60 sieve.

Moderately coarse powder (No.40): All particles pass through a No.40 sieveand not more than 40% through a No.80 sieve.

Fine powder (No.60): All particles pass through a No.60 sieve and not morethan 40% through a No.100 sieve.

Very fine powder: There is no limit as to greater fineness.

Size Range: 50 to 100 μm.

Advantages:1. Sieving is cheap, simple and rapid with little variation between operators.2. Micromesh sieves are available for extending the lower limit of 10 micron.

Disadvantages:1. Particles may be attached electro statically to form aggregates.2. Sometimes humidity affects particles of hygroscopic materials and lead to

aggregation.Applications:

i. Sieves are generally used for grading coarser particle.ii. Widely used for measuring particle size.

PARTICLE VOLUME MEASUREMENT (fig)Principle:

The particle size in the subsieve range may be obtained by gravity sedimentationas expressed in stokes law: -

V = = dst2 (ρs ρ0) / 18 ηo


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Where,v = rate of settingh = total distancet = falling timeρs = density of the particleρ0= density of the dispersion mediumg = acceleration due to gravityηo = viscosity of the medium

dst = stokes diameter of the particle

The equation holds exactly for spheres falling freely without hindrance and at aconstant rate. The law is applicable to irregularly shaped particles of varioussizes.

The particle must not be clumped or aggregated together in the suspensionssince such clumps would fall more rapidly than the individual particles. Toovercome this problem proper deflocculated agent must be used with thesample.

For stokes law, the flow of dispersion medium around the particle as itssediments is Laminar or Streamline.

The Renynolds number must not be greater than 0.2

Size Range:Particle size must be 10 to 50 micrometer.

Apparatus:Several methods based on sedimentation are used. The principle methods are

pipette method, the balance method, the hydrometer method.

Pipette Method:Pipette method is carried out by Andresen apparatus.

Andresen Apparatus It usually consists of a 550ml vessel containing a 10ml. Pipette sealed into a ground glass stopper. A 1% or 2% suspension of the particles in a medium. Containing a suitable deflocculating agent is introduced into the vessel and

brought to the 550ml mark. The stoppered vessel is shaken to distribute theparticles uniformly throughout the suspension and the apparatus with pipette


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in place is clamped securely in a constant temperature bath. At various intervals10ml samples are withdrawn and discharged by means of the two waystopcock. The samples are evaporated and weighted or analyzed by otherappropriate.

Means, correcting for the deflocculating agent that has been added. Theparticle diameter corresponding to the various time periods is calculated fromstokes law.

Advantage:1. It is very effective method for determining the particle size of emulsion and

suspension.2. It may be used over a size range from 1 – 200 microns.

Disadvantages:It does not give a clean split of particle size.

Application:It is used to obtain a size weight distribution curve.

Particle Shape & Surface Area

The shape and surface area of the particles is necessary to determine – The shape affects the flow and packing properties of a powder.

The surface area put unit weight or volume is an important characteristic of apowder when one understands surface adsorption and dissolution studies.

PARTICLE SHAPEA spherical particle is characterized completely by its diameter. As the particlebecome more asymmetric, it becomes increasingly difficult to assign a meaningfuldiameter to the particle.

It is simple matter to obtain the surface area or volume of a sphere for such aparticle –

Surface area = πd2

Volume = πd3/6Here, d is the diameter. The surface area and the volume of a spherical particle areproportional to the square and cube, respectively of the diameter.

SPECIFIC SURFCE

We know that the surface area or volume of a sphere or such for aparticle –


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It is simple matter to obtain the surface area or volume of a sphere forsuch a particle –

Surface area = πd2

Volume = πd3/6

The specific surface is the surface area per unit volume (Sv) or per unit weight

(Sw).For asymmetric particles where the characteristics dimension is not defined

S =

Here n is the number of particles. The surface area per unit weight is therefore

n which ρ = true density of the particles. Substituting for equation 1 in 2 we get,

characteristic of specific surface. When the particles are spherical we can write theequation –

Science, αs/αv = 6.0 for a sphere.

Related MathExample 2.4: Determine the total surface of 5 g of an antibiotic powder in whichparticles have an average diameter dvs of 2μm and a true density of 2.4g/cm3.Assume that the particles are sphere.Solution

Volume surface mean diameter of the particles (dvs) = 2μm= 2 × 10-4 cm

True density of the powder (ρ) = 2.4 g/cm3

Specific surface per unit weight,

Total Surface of 1 g of powder = 1.25× 104 cm2


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Total surface of 5 g of powder = (5 × 1.25× 104) cm2

= 6.25× 104 cm2

Example 2.5: Determine the specific surface, Sw and Sv of a sample of spray driedlactose having spherical particles of diameter (dvs)3.0μm and the true density of1.54g/cm3.Solution

Volume surface mean diameter (dvs) = 3.0μm= 3 × 10-4 cm

True density (ρ) = 1.54 g/cm3

Specific surface per unit weight,

Specific surface per unit volume,Sv = 6/d

= 6/3× 10-4 cm2/cm3

= 2 × 10-4 cm2/cm3

Methods for determining Surface Area

Two methods are commonly available that permit direct calculation of surfacearea which are – The amount of gas or liquid solute that is adsorbed on to the sample of the

powder to form a monolayer is a direct function of the surface area of thesample.

The second method depends on the fact that the rate at which a gas or liquidpermeates a bed of powder is related, among other factors, to the surface areaexposed to the permeate.

AIR PERMEABILITY METHODThe principle resistance to flow of a liquid, such as air, through a plug ofcompacted powder is the surface area of the powder. The greater the surface areaper gram of powders, Sw, the greater the resistance to flow. Hence, permeability,for a given pressure drop across the plug, is inversely.

Proportional to specific surface; measurement of the former provides a means of

estimating this parameter. From surface diameter equation we can calculate, dvs. Aplug of power may be regarded as a series of capillaries whose diameter is related


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to the average particle size. This internal surface of the capillaries is a function ofthe surface area of the particles. According to Poiseuille’s equation,

Where v is the volume of air flowing through a capillary of internal diameter dand length l in t seconds under a pressure difference of ∆P. the viscosity of thefluid (air) is η poise.

In particles, the flow rate through the plug, or bed, is also affected by –1) The degree of compression of the particles and2) The irregularity of the capillaries.

The more compact the plug, the lower the porosity, which is ratio of the totalspace between the particles to the total volume of the plug. The irregularity ofthe capillaries means that they are longer than the length of the plug and arenot circular.

Derived porosities of powdersParticle size distribution and surface area are two fundamental properties of

powders. From these properties of powders a number of derived properties canbe obtained.

POROSITY OF POWDERSFor a non-porous material, the bulk volume is equal to the true volume. Mostpharmaceutical solids are porous i.e., they have internal pores or capillary spaceand hence the bulk volume is greater than the true volume. The volume of thespaces known as the void volume is given by

v = vb - vp

Where, vb is the bulk volume and vp is the true volume of the particles.

The porosity or voids ε, is defined as the ratio of the void volume to the bulkvolume of the powder packing. Thus,

Porosity is expressed as percentage i.e., s × 100

Packing Arrangement in Powder Beds A bed or heap of powder consists of a number of particles each in contact with

its neighbors. Theoretically; two types of packing are possible. These include theclosest or rhombohedra packing and the most open or loosest or cubical


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packing. The fraction of the total volume occupied by the free space betweenthe particles is the porosity.

If the powder bed consists of spherical particles, theoretical porosity of 26% ispossible in the closest packing and 48% in loosest packing. However in actualsituations, packing between these, two limits are encountered andpharmaceutical powders have porosities ranging from 30 and 50%.

In certain cases, when the particle of varying sizes is present, porosity lower thanthe theoretical minimum of 26% is also possible. This is because small particles fitin the void spaces thereby giving a reduced porosity. On the other hand if thepowder contains floccules or aggregates the

Porosity may be goes mat beyond the theoretical maximum of 48% due to thelarge void spaces with entrapped air. In case of highly compressed crystallinematerials, porosities less than 1% are also possible.

DENSITY OF POWDERSDensity is universally defined as the mass per unit volume. However, difficulty indetermining the true volume, of powders arises because these contain microscopiccracks, internal pores and capillary spaces. Based on the method of determination,three types of densities can be distinguished.

1) True density i.e., density of the material exclusive of pores, etc.2) Granule density as determined by the displacement of mercury which does

not penetrate at ordinary pressure into pores smaller than about 10μm.3) Bulk density as determined from the bulk volume and the weight of a drug

powder in a graduated cylinder.

1) True DensityIt is the density of the actual solid material devoid of free spaces and is definedas the ratio of the given mass of a powder and its true volume.

True volume = Bulk volume – Void volumeThe true density of a powder may be determined by the following methods: -

a) Liquid displacement method: In this method a liquid in which the solid isinsoluble is generally used. The powder whose density is to be determined isadded into a standard flask of known volume and the weight determined. Anordinary pycnometer is generally suitable for the purpose. Now a liquid inwhich the powder 3s insoluble is introduced into the flask. The liquid fills upthe void spaces between the particles until the whole volume of the flask is


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weighted the flask are emptied and only the liquid is filled into it and weighed.The true density is obtained as the ratio between the weight of the materialand the weight of the liquid it displaces.

b) Gas displacement method: In this method a gas such as helium or hydrogen isused instead of a liquid is that it penetrates into the smallest pores and crevicesand gives a better approximation of the true volume of the material.In this method a weighted quantity of the powder material is introduced into asample tube and the adsorbed gases are removed from the powder bydegassing procedure. Helium gas, which is not absorbed by the powder, is thenintroduced into the tube. The pressure difference before and after theintroduction of helium is determined with the help of a manometer. Byapplying the gas law, the volume of helium surrounding the particles of thepowder aid penetrating into the pore, is calculated. The difference between thevolumes of helium filling the presence of powder gives the true volume of thepowder. The ratio of the mass of the powder and its true volume gives the truedensity.

2) Granule Density (p)Granule density is the ratio of the mass of the granular powder and the volumeoccupied by the granular material together with its intra particle spaces.

The granule density is also determined in a manner similar to liquiddisplacement method but mercury is used as the displacement liquid sincemercury does not enter the internal pores of the particles. The volume of thematerial thus obtained is the true volume of the material along with thevolume occupied by the intra particle spaces.

3) Bulk density (Pb)Bulk density of a powder is defined as the ratio of the mass of the powder andits bulk volume.

For determination of bulk density, a weighted quantity of powder material isintroduced into a graduated measuring cylinder and tapped mechanically eithermanually or using s tapping device till a constant volume is obtained. Thisvolume, is known as the bulk volume of the powder s noted and includes the


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true volume of the powder as well as the volume occupied by the inter particleand intra particle spaces.

The bulk density of a powder depends only on the particle size distribution,particle shape and the packing arrangement. The intra particle porosity of thegranule is given by –

Where,Vp is the true volume of the solid particles.vg is the volume of the particles together with the intra particle pores.

Interspace or void porosity of a powder of porous granules is the relative volumeof intra space void to the bulk volume of the powder exclusive of the intraparticle pores.

Where,Vb is the bulk volume, i.e., w/ρb


12Vp is the volume of the solid material itself, i.e., w/ρW is the mass of the power.ρ is the true density.ρb is the bulk density.

Or,

BulkinessThe reciprocal of bulk density is known as the bulk or bulkiness or specific bulk

volume. Bulkiness usually increases with a decrease in particle size. However, in amixture of particles with different sizes, the bulkiness may get reduced since thesmaller particles may shift between the larger ones.

It is useful property to be considered while choosing a suitable container forpackaging of bulk powders or during filling of drug powders into capsules.

Flow Properties of PowdersThe flow properties of powders is an important parameter to be considered in

the production of pharmaceutical dosage forms since most of the processes such asuniform filling of dies during tableting and proper filling of capsules during capsulefilling directly depend on the flow properties of the powder mass. Other processessuch as gravity feeding of powders or their pneumatic and hydraulic transfer fromone place to another also depend on the flow properties.

Powders may be free flowing or may have a poor flow. The poor flow inpowders is generally attributed to one or more of the following reasons: -

i) Cohesiveness or stickiness between particles due to presence of Van dar walls,surface tension and electrostatic forces.

ii) Adhesion between the particles and the container wall due to the aboveforces.

iii) Friction between particles due to surface roughness.iv) Physical interlocking of particles specially if these is of irregular shape.

The cohesiveness of particles has been found to depend upon a number of factorsincluding particle size and shape, the density or porosity of the powder and thepresence of adsorbed materials on the powder surface. Thus, very fine particles(less than 10 microns in size) tend to be more cohesive due to their larger surfacearea and dense materials tend to be less cohesive than lighter ones. Poor flow


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sometimes results from presence of moisture which increases the cohesiveness.Drying of granules can easily remove this problem.

Poorly flowing powders or granulations present many difficulties to thepharmaceutical industries. The production of uniform dosage forms such as tablets,and capsules depends upon several granular properties. It is generally seen that asthe granule size is reduced, the problem of tablet weight variation also getsreduced. The particle size and size distribution also affects the internal flow andsegregation of granulation. During the flow of tablet granulation through thehopper, granule remixing may take place and the fines being heavier per unitvolume may segregate from coarse granules. This will cause a decrease in thetablet weight during the latter portion of the compression process.

Assessment of flow Properties of PowdersFlow properties of powders generally assed by determining the angle of repose

of the powders. It is defined as the maximum angle possible between the surfaceof a pile of powder and the horizontal plane. The angle of repose is determinedby allowing a mass of powder to flow freely through an orifice from a certainheight and form a conical heap on the horizontal surface. As the heap is formedthe particles slip and roll over each other until the mutual friction between theparticles just balances the gravitational force, the angle which the heap forms withthe horizontal surface is the angle of repose and is determined by the formula: -

tanθ = h/rWhere,θ is the angle of repose.

h is the height of the heap of powder andr is the radius of the base of the heap of powder.

Asngle of reposeAngle of repose is a function of the surface roughness. The rougher and more

irregular the surface of particles, the more (or higher) the angle of repose. As theparticle becomes less and less spherical, the angle of repose increases while thebulk density and flow ability decreases. Generally, the angle of repose increaseswith a decrease in particle size and vicevirsa. Also addition of glidants such as, Talcin low concentration (-1%) decrease the angle of repose.

Generally powders with angle of repose more than 50° have unsatisfactory flowproperties while those with minimum angle close to 25° corresponds to very goodflow properties.


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Improvement of flow PropertiesFlow properties of powders can be improved by one or more of the following

methods.1. Altering the particle size:

Increasing the average particle size of particles improves the flow propertiesdue to reduction in the cohesive forces. During tableting, fine powders areconverted to coarse granules in order to impart good flow properties ofthem.

2. Removal or Addition of fines: Presence of a small proportion of fines in apowder or granular mass may improve the flow properties by filling up thepits and crevices on the surface of particles. On the other hand, largerproportion of fines may retard the floe properties. Hence, an optimum,concentration of fines is desirable for the best results.

3. Altering the particle shape and texture: Spherical particles tend to have betterflow ability as compared to irregular particles. Hence, techniques like spraydrying may be used to give spherical particles with good flow properties.Alteration of crystallization conditions may also produce particles of thedesired shape and texture.

4. Altering the surface forces: Reduction of electro static charges on particlesurface by reducing frictional contacts such as during transfer or duringprocesses such as sieving can improve the flow properties.

5. Removing extra moisture: Drying of powders in order to remove themoisture from surfaces can improve the flow properties by decreasingcohesiveness.

6. Adding flow activators or glidants: flow properties of pharmaceuticalpowders may be improved significantly by the addition of materials knmvnas glidants. These acy by forming a thin uniform film on the surface of

Angle of repose (θ) (degrees) Flow properties<25 Excellent

25 – 30 Good

30 – 40 Satisfactory

40 – 50 Poor>50 Very poor


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particles to reduce the adhesion and cohesion between particles. Example ofsuch materials includes magnesium stearate, starch and talc. The optimumconcentration of glidents has been experimentally demonstrated to begenerally 1% or less and above this concentration usually there is a decreasein flow rate. Colloidal silicon dioxide is another flow activator with a veryhigh specific surface area which act by reducing the bulk density of tightlypacked powders.

Micro Me Retics

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