Chapter 18 Micromeritics

MICROMERETICS

The science and technology of small particles

Fundamental properties of particles

1. Size of particle2. Surface area of the particle

(particle shape)

POLYDISPERSE SYSTEM

• Collection of particles of more than one size• Properties can be described in terms of:

1. Shape and surface area of individual particles

2. The size range and number or weight of particles

MONODISPERSE SYSTEM

• Particles of approximately uniform sizeUSES1. Diagnostic tests2. Particle size standards for particle analyzers3. For accurate determination of pore size in filters4. As uniformly sized surfaces upon which antigens may

be coated for effective immunization5. For instrument calibration and quality control in the

manufacture of submicron-sized products such as liposomes, nanoparticles, and microemulsions

METHODS OF DETERMINING PARTICLE SIZE

1. OPTICAL MICROSCOPY2. SIEVING3. SEDIMENTATION4. PARTICLE VOLUME MEASUREMENT

1. OPTICAL MICROSCOPY

• Uses an ordinary microscope for particle measurement in the range of 0.2 m to 100 m.

• Presence of agglomeration and particles of more than one component may be detected

• The diameter is obtained only from two dimensions: length and breadth, the thickness/depth in not measured.

2. SIEVING

• Uses standard sieves• Generally used for grading coarser particles• May be employed for screening materials as

fine as 44 m (No. 325 sieve)CAUSES OF ERRORS1. Sieve loading2. Duration and intensity of agitationDisadvantage: “Attrition” of particles (rubbing

together/pulverization)

POWDERS OF VEGETABLE AND ANIMAL DRUGS ARE OFFICIALLY DEFINED AS:

• VERY COARSE (#8) – all particles pass through no.8 sieve and not more than 20 % through sieve no. 60.

• COARSE (#20) – all particles pass through no.20 sieve and not more than 40 % through sieve no. 60.

• MODERATELY COARSE (#40) - all particles pass through no.40 sieve and not more than 40 % through sieve no. 80.

• FINE (#60) - all particles pass through no.60 sieve and not more than 40 % through sieve no. 100.

• VERY FINE (#80) – all particles pass through a no. 80 sieve. There is no limit as to greater fineness.

POWDERS OF CHEMICAL DRUGS ARE OFFICIALLY DEFINED AS:

• COARSE (#20) – all particles pass through no.20 sieve and not more than 40 % through sieve no. 60.

• MODERATELY COARSE (#40) - all particles pass through no.40 sieve and not more than 60 % through sieve no. 60.

• FINE (#80) - all particles pass through no.80 sieve and there is no limit as to greater fineness.

• VERY FINE (#120) – all particles pass through a no. 120 sieve. There is no limit as to greater fineness.

SEDIMENTATION

• The particles size may be obtained by gravity sedimentation as expressed by STOKE’S LAW.

• Uses Andreasen pipet

dst = 18 h

(i - e)gt

PARTICLE VOLUME MEASUREMENT

• Uses Coulter Counter☺An instrument used to measure the volume of particles☺Capable of counting particles at the rate of approximately 4000 per second, thus both gross counts and particle size distributions are obtained in relatively short period of time

Average Particle size determination

BY WEIGHT• Sieving method• Light scattering• Sedimentation

BY VOLUME• Light scattering • Electronic senzing

zone• Light obstruction• Air permeation• Optical microscopy

PARTICLE SHAPE

• Sphere• Affects the flow and packing of a powder

SURFACE AREA• Determined by the shape of particles• Affects adsorption and dissolution rateSPECIFIC SURFACE – surface area per unit

volume or per unit weight

METHODS OF DETERMINING SURFACE AREA

1. ADSORPTION METHOD• Uses Quantasorb 2. AIR PERMEABILITY METHOD• Uses Fisher subsieve sizer

Powders of large surface area are good adsorbents

DERIVED PROPERTIES OF POWDERS

1. POROSITY (VOIDS)Defined as the ratio of the void

volume to the bulk volume of the packingVoid volume = volume of spacesBulk volume = volume occupied

total = (Vb – Vp)/Vb

intraparticle = (Vg – Vp)/Vg

interspace = (Vb – Vg)/Vb

POROSITY CALCULATIONS

1. Calculate the porosity of a sample of aluminum oxide having a true density of 4.0 g/cm3. When 75 g of the powder was placed in a graduated cylinder, The Al2O3 was found to have a bulk volume of 62 cm3.

= Vb –Vp Vb

2. The true density of Aspirin is 1.37 and the granule density is 1.33. What is the porosity or percent void spaces within the granules?

intraparticle = Vg – Vp Vg

intraparticle = 1 – granule density true density

3. A 1-g sample of a granular powder has a true volume of 0.3 cm3; volume of intraparticle pores = 0.1 cm3; volume of spaces between particles = 1.6 cm3. Calculate the interspace porosity.Vg = 0.3 + 0.1 = 0.4 cm3

Vb = 0.3 + 0.1 + 1.6 = 2.0 cm3

interspace = Vb – Vg = 1 - bulk density___

Vb granule density

2. PACKING ARRANGEMENT

TWO IDEAL PACKING ARRANGEMENTS1. CLOSEST PACKING (OR

RHOMBOHEDRAL) angles of 60° and 120° are common porosity is 26%2. MOST OPEN, LOOSEST, OR CUBIC PACKING Packed at 90° to each other

resulting to a porosity of 47-48%

III. DENSITIES OF PARTICLES

TRUE DENSITY – is the density of the actual solid, exclusive of voids and intraparticle pores

GRANULE DENSITY – density of the powder particles together with their intraparticle pores.

BULK DENSITY – density of material as determined from the bulk volume and weight of a dry powder

IV. BULKINESSOr BULK, is the specific bulk volumeReciprocal of bulk densityAn important consideration in

packaging powdersBulkiness increases with a decrease

in particle size

V. FLOW PROPERTIES

FLOW PROPERTIES EXHIBITED BY POWDERS1. PLASTIC FLOW2. DILATANT FLOWFACTORS AFFECTING FLOW PROPERTIES3. PARTICLE SIZE AND SHAPE 250-2000m = free flowing 75 – 250 m = flow freely or cause

problem depending on shape Very fine particles (less than 10 m) = do

not flow freely as large particles

Particle shape and flow properties

Spherical shape flow better than needle particles

Elongated or flat particles tend to pack resulting to high porosity powders

Free flowing

FACTORS AFFECTING FLOW PROPERTIES

2. POROSITY AND DENSITYHigh density, low porosity = FREE

FLOWING3. SURFACE ROUGHNESS Leads to poor flow characteristics

ANGLE OF REPOSEA technique for estimating the

flowability of a powderMeasures the frictional forces in a

loose powderThe maximum angle possible

between the surface of a pile of powder and the horizontal plane

ANGLE OF REPOSEtan = h/rWhere

h = height of the powder coner = radius of the powder cone

tan = 3.3cm/ 4.5 cm

tan = 0.7333333= arc tan

0.73333= 36.25°

9.0 cm

Powders of low repose angles are FREE

FLOWING; high angle of repose poorly flow and has low bulk density

FREE FLOWING POWDERS

Characterized by “ dustibility’Examples:

Talcum= 57%Potato starch = 27%Fine charcoal = 23%

COHESIVE POWDERS

Cohesiveness may be a result of:1. Presence of “fines”2. Presence of moistureMaterials used to improve flow

properties are called GLIDANTS

Example: Magnesium stearate, starch, talc

VI. Compaction/ DILATANCY

Dilatancy is the expansion of powder under the influence of stress

Porosity of powders increases upon compression

Important in pharmaceutical tableting