MICROMERITICS

Micromeritics:
Definition: It is the science and technology of small particles. *The unit of particle size used is the micrometer, μm, micron, μ, and equal to 10-6 m. As particle size decreases , the surface area increases

Micromeritics (Cont.):
The knowledge and control of the size of particles is of importance in pharmacy and materials science. The size & hence the surface area of a particle can be related to the physical, chemical & pharmacologic properties of drugs. 1- Release & dissolution: Particle size & surface area influence the release of a drug from a dosage form. Higher surface area allows intimate contact of the drug with the dissolution fluids in vivo & increases the drug solubility & dissolution.

Physical stability: The particle size in a formulation influences the physical stability of the suspensions & emulsions.Absorption & drug action: Particle size & surface area influence the drug absorption & subsequently the therapeutic action.Micromeritics (Cont. Smaller the size of the particle. 3. faster the absorption & hence quicker & greater the drug action. better the physical stability of the dosage form. . Higher the dissolution.): 2.

): 4.Micromeritics (Cont. .Dose uniformity: Good flow properties of granules & powders are important in the manufacturing of tablets & capsules.

Methods for determining particle size: 1. .2 –100 um): The microscope eyepiece is fitted with a micrometer by which the size of the particles may be estimated.Optical microscopy (range: 0.

Methods for determining particle size (Cont. . -The fraction of the material between pairs of sieve sizes is determined by weighing the residue on each sieve.Sieving (range: 40 – 9500μm ): -Standard sized sieves are available to cover a wide range of sizes. -The stack of sieves is mechanically shaken to promote the passage of the solids. -The result achieved will depend on the duration of the agitation and the manner of the agitation.): 2. 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.

Methods for determining particle size (Cont.Sedimentation (range: .08 –300μm): by measuring the terminal settling velocity of particles through a liquid medium in a gravitational centrifugal environment using Andreasen apparatus. .): 3.

Counting is done by a computer.When a particle passes through the capillary there is a momentary peak in the resistance.300 um): .Methods for determining particle size (Cont.Particle volume measurement (range: .): 4. .5 . This suspension is then made to flow through a short insulated capillary section between two electrodes and the resistance of the system is measured. .In this type of machine the powder is suspended in an electrolyte solution . the amplitude of the peak is proportional to the particle size.

Derived properties of powders: .

• The porosity or voids ε of powder is determined as the ratio of void volume to bulk volume. • bulk volume = true volume + volume of spaces between particles.Porosity: Suppose a nonporous powder. the void volume.Derived properties of powders: 1.Vp • Vp is the true volume of particles. ε Vb – Vp Vb = 1 x 100 . is placed in a graduated cylinder: • the total volume occupied is known as the bulk volume Vb . Vp Vb . • The volume of the spaces. V = Vb . • Porosity =ε= • Porosity is frequently expressed in percent.

Porosity .

Porosity (Cont.3g was found to have a bulk volume of 82 cm3 when placed in a 100-ml graduated cylinder.): Example A sample of calcium oxide powder with a true density of 3.203 and weighing 131. Calculate the porosity ?? .1.

3 g / (3.203 g/cm3 ) = 41cm3 ε= Vb – Vp Vb = 82 – 41 82 ε = 0.Porosity (Cont.5 or 50% .): Answer The volume of the particle is 131.1.

Density Intraparticular pores Interparticular pores .

of a sample excludes the volume of the pores and voids within the sample. or absolute density.Derived properties of powders (Cont. .): 2. B.bulk density (w/v) the bulk density value includes the volume of all of the pores within the sample.Density is defined as weight per unit volume (W/V).Densities of particles: . Types of densities: A.true density The true density.

the powder volume decreases and the tapped density increases. . particles gradually pack more efficiently.Densities of particles • During tapping.

 In mixture of materials of different sizes.Bulkiness = Specific bulk volume = reciprocal of bulk density:  It is an important consideration in the packaging of powders. and the lightest (bulkiest) type require a container about 13 times larger than that needed for the heaviest variety.1 to 1. (Bulkiness increases with a decrease in particle size).Derived properties of powders (Cont. the smaller particles sift between the larger ones and tend to reduce bulkiness.  The bulk density of calcium carbonate vary from 0. .): 3.3.

Many common manufacturing problems are attributed to powder flow: 1. 2.Uneven powder flow → increase particle’s friction with die wall causing lubrication problems. .Derived properties of powders (Cont. .Powder transfer through large equipment such as hopper. 3.Uneven powder flow → excess entrapped air within powders → capping or lamination.): 4.Flow properties: • Powders may be free-flowing or cohesive (“sticky”). and increase dust contamination risks during powder transfer.

): .Derived properties of powders (Cont.

Derived properties of powders (Cont.non-uniformity (segregation) in blending .): 4.

.which for example result in caking tendencies within a vial or bag after shipping or storage time.): 5. encapsulation and vial filling which affect the weight uniformity of the dose (under or over dosage).specifically just before the creation of individual doses such as during tableting.Separation of small quantity of the powder from the bulk.Derived properties of powders (Cont.Powder storage. 6.

powder flow problems .

Tests to evaluate the flowability of a powder: 1. Carr’s index (%) = Tapped density – Poured or bulk density x 100 Tapped density Bulk density = weight / bulk volume Tapped density = weight / true volume .Carr’s compressibility index A volume of powder is filled into a graduated glass cylinder and repeatedly tapped for a known duration. The volume of powder after tapping is measured.

): Relationship between powder flowability and % compressibility Flow description Excellent flow Good Fair Poor Very poor % compressibility 5 – 15 16 – 18 19 – 21 22 – 35 36 – 40 Extremely poor > 40 .Carr’s compressibility index (Cont.1.

5 added glidant doesn’t improve flow.25 indicates good flow ( = 20% Carr ).5 indicates poor flow ( = 33% Carr ). . more cohesive.): 2.Tests to evaluate the flowability of a powder (Cont. **Between 1. such as coarse spheres. **Value greater than 1. added glidant normally improves flow.Hausner ratio: Tapped density Hausner ratio = Poured or bulk density Hausner ratio was related to interparticle friction: **Value less than 1. less free-flowing powders such as flakes.25 and 1. ** > 1. The powder with low interparticle friction.5.

Tests to evaluate the flowability of a powder (Cont.): 3. φ = the maximum angle possible between the surface of a pile of powder and horizontal plane = coefficient of friction μ between the particles: tan φ = μ tan φ = h / r r=d/2 .The angle of repose φ: The frictional forces in a loose powder can be measured by the angle of repose φ.

3.     Angle of repose less than 20 (excellent flow) Angle of repose between 20-30 (good flow) Angle of repose between 30-34 (Pass flow) Angle of repose greater than 40 (poor flow) ***The rougher and more irregular the surface of the particles.): . . . the higher will be the angle of repose.The user normally selects the funnel orifice through which the powder flows slowly and reasonably constantly.The angle of repose φ (Cont.The sample is poured onto a horizontal surface and the angle of the resulting pyramid is measured.

Factors affecting the flow properties of powders: Improvement of Powder Flowability Particle’s size & Distribution Particle Shape & texture Surface forces Flow Activators .

Factors affecting the flow properties of powders (Cont.): Alteration of 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. such as occurs in granulation.  The size distribution can also be altered to improve flowability by removing a proportion of the fine particle fraction or by increasing the proportion of coarser particles. .

Factors affecting the flow properties of powders (Cont. . Particle's texture: particles with very rough surfaces will be more cohesive and have a greater tendency to interlock than smooth surfaced particles. Spherical particles are obtained by spray drying. or by temperature cycling crystallization.): Alteration of Particle Shape & texture Particle’s Shape: Generally. more spherical particles have better flow properties than more irregular particles.

.Drying the particles will reduce the cohesiveness and improve the flow. . stored and processed under low humidity conditions. .Moisture content of particle greatly affects powder’s flowability. .Factors affecting the flow properties of powders (Cont.Reduction of electrostatic charges can improve powder flowability. Electrostatic charges can be reduced by altering process conditions to reduce frictional contacts.Hygroscopic powders. -Adsorbed surface moisture films tend to increase bulk density and reduce porosity.): Alteration of Surface Forces .

Flow activators are commonly referred as glidants. e.Factors affecting the flow properties of powders (Cont.): Formulation additives ( Flow activators) .Flow activators improve the flowability of powders by reducing adhesion and cohesion. .g. talc. maize starch and magnesium stearate .