Micromeritics ppt vijay sharma
- 1. Micromeritics Prepared By:- Vijay Sharma Asso. Prof. , Goenka college of Pharmacy, Lachhmangarh, Sikar
- 2. The term micromeritics was given to the science and technology of small particles by J. M. DallaValle. It involves the characterization of individual particles, particle size distribution and powders. Particles are characterized by the following properties. Size Shape Volume Surface area Density Porosity Flow Particle size is normally denoted in micrometers μm. 1 μm = 10-3mm or 10-6 m. The unit of particle size used in the micrometer (µm), micron (µ) and equal to 10-6 m.
- 3. Need/ Importance/ Application of Micromeritics • Drug release and dissolution • Absorption and drug action • Physical stability • Dose uniformity • Extraction and acceleration • Spreadibility and performance of cosmetics • Chemical and physical Properties • Taste , colour and texture
- 4. Properties of Powders • Fundamental properties :-These properties relate to the individual particle. Particle size and size distribution Particle shape Particle surface area Particle weight Particle number • Derived properties :- They are dependent on fundamental properties & define the factors relating to their measurement. Density of powders (a) bulk density (b)tapped density (c) granular density (d)true density Flow properties of powders Porosity Bulkiness
- 5. Particles - Characteristics • Particles characteristics influence the dissolution rate, absorption rate, content uniformity, taste, texture, color & stability. • Each particle can be characterized & expressed by the following properties: – Size – Shape – Volume – Surface area
- 6. Particle size • The shape of particles present in a powder is normally not spherical, but symmetrical (uneven). • particle size is expressed as the diameter which is related to an equivalent spherical diameter. • Size of the particles may be expressed as follows: Surface diameter, ds: is the diameter of a sphere having the same surface area as that of the asymmetric particle. Volume diameter,dv: is the diameter of a sphere having same volume as that of the asymmetric particle. Projected diameter, dp : is the diameter of a sphere having the same area of the asymmetric particle as observed under a microscope. Stokes’ diameter, dst : is the diameter of an equivalent sphere undergoing sedimentation at the same rate as the asymmtric particle. Sieve diameter, dsieve : is the diameter of a sphere that passes through the same sieve aperture as the asymmetric particle. Volume-surface diameter, dvs : is the diameter of a sphere that has same volume to surface area ratio as the asymmetric particle.
- 7. Particle Shape • According to their shape particle divided are into two groups. 1 . Symmetrical Particle 2 . Asymmetrical Particle • Particle shape is related to geometric shape will influence the surface regularity. • Particle shape will influence the surface area, flowof particles, packing & compaction properties of the particles. • The surface area per unit weight& unit volume are important in the studies of absorption & dissolution. • A sphere has minimum surface area per unit volume. • Therefore, these properties can be compared for spheres & asymmetric particles, in order to decide the shape. • Shape factor of the particle can be expressed as the ratio of surface to volume factor . Shape factor value = 6 represent sphere Shape factor value > 6 represent asymmetric
- 8. Particle Number • The number of particles present in a dosage form should remain constant in order to maintain dose uniformity. • The number of drug particles vis-à-vis number of particles of other ingredients should be maintained constant for a given weight of dosage form. • Lager the number of drug particles, smaller is the error. • Error are large, when the number of drug particles are small. • The number of particle per unit weight, N, is expressed in terms of volume number mean diameter ,dvn
- 9. Particle Size Distribution • In a simple of powder, particle of various size are present. This distribution of particle of various size in a sample is known as Particle size distribution OR • Particle size distribution of a powder or granular material dispersed in fluid is the relative amount typically by mass present according to size. its also called grain size distribution. Types of particle size distribution There are two types of particle size of distribution. 1. Number particle size distribution In this technique we count the number of particle in specific size range. The number of particle are usually calculated by microscopic technique.
- 10. 2. Weight Particle Size Distribution In this technique we weight the particle in specific size range. The weight of the particle is usually calculated by sedimentation or sieving method. Frequency Distribution Curve • If the number of weight fraction is plotted against their size range a frequency curve is obtained. This curve is known as particle size curve or frequency distribution curve or histogram. • Such plot giving a visible representation of the distribution that an average diameter can not achieve. • This is important b/c it is possible that simple have the same diameter but different distribution .
- 11. This is important because it is possible that simple have the same diameter but different distribution.
- 12. Surface Area Determination Specific surface: surface area of a powder can be calculated using particle size data which are obtained by one of the methods mention already. Specific surface is defined as the surface area per unit weight (Sw) or unit volume(Sv) of the material. Estimation of Sv: Sv = Surface area of particles / Volume of particles = No. of particles × surface area of each particle / No. of particles × Volume of each particle Estimation of Sw: Sw = Surface area / Weight = Surface area/density × Volume
- 13. The commonly used methods are: 1. Adsorption method 2. Air Permeability method 1. Adsorption Method: • Particles having large specific surfaces are good adsorbents of gases & solutes from solution. • Amount of gas that is adsorbed to form a monomolecular layer on the adsorbent is a function of surface area of the powder. • This principle is used to estimate the specific surface. • This method is also used to estimate surface diameter, ds.
- 14. • Surface area is most commonly determined based on • Brunauer-Emmett-Teller (BET) theory of adsorption. • Most substances adsorb a monomolecular layer of gas under certain conditions of partial pressure of gas and temperature. • The adsorption process is carried out at liquid nitrogen temperatures -196˚C. • Once surface adsorption has reached equilibrium, the sample is heated at RT and Nitrogen gas is desorbed. Its volume is measured. • As each N2 mol. occupies fixed area, one can compute surface area of pre-weighed sample.
- 15. 2. Air Permeability method • This method also used to estimate surface diameter, ds. • This method is useful in controlling batch to batch variations in production of powders. • Powder is packed in sample holder • Packing appears as series of capillaries • Air is allowed to pass through the capillaries at constant pressure • Resistance is created as air passes through capillaries thus causing pressure drop. • Greater the surface area greater the resistance • Air permeability is inversely proportional to the surface area
- 16. • This method is official in I.P. Fisher subsieve sizer instrument is commercially available. • Assembling of the apparatus is shown in figure. • It consist of a sample tube containing the packed powder sample with one end connected to an air pump through a constant pressure regulator. • The other end is attached to a calibrated manometer containing a suitable liquid of low viscosity & negligible vapor pressure. • The air pump builds up air pressure & is connected to a constant pressure regulator. • Air is passed through the dryer to remove any moisture. • Air then allowed to flow through the packed powder in the sample tube.
- 17. •The flow of air is measured by the manometer. •The level of the fluid in the manometer indicates the average diameter of the particles. •The porosity of the powder (ε) & viscosity (η) are estimated separately.
- 18. Powders- Characteristics • Powder is consider as a collection of particles. • Therefore, the properties that are ascribed to a particle, can as well be applied to powder. • At the same time, particles also collectively contribute certain properties to the powder. • Thus, powder is characterized & expressed by the following properties: Powder size Flow properties Volume Particle number Density Surface area
- 19. • The powder contains particles of one size, the powder is termed mono size or monodisperse. • Mono-size particles are important in pharmacy in the following areas: • Standardization of instruments, particle size analyser. • Accurate determination of pore size in case of filters. • For effective immunization, normally, antigens are made to adsorb on uniform sized particles. • For diagnostic purposes. • Most of the pharmaceutical powders are polidisperse, i.e., contain particles of different sizes.
- 20. Particle size determination methods Selection of a method largely depend on its intended applications, desired type of diameter & type of distribution required. 1. Optical microscopy (range: 0.2-100 µm). 2. Sieving (range: 50-1500 µm). 3. Sedimentation (range: 1.0-200 µm). 4. Particle volume measurement (range: 0.5-500 µm). Particle size Method 1 mm Electron microscope, ultracentrifuge, adsorption 1 – 100 mm Optical microscope, sedimentation, coulter counter, air permeability >50 mm Sieving
- 21. 1. Optical Microscopy • Particle size in the range of the 0.2-100µm can be measured by optical microscopy. • In this method, the size is expressed as dp(Pojected diameter), which describes the diameter of a sphere having the same area as the asymmetric particle when observed under a microscope. • This method directly gives number distribution, which can be further converted to weight distribution. • The optical microscope has a limited resolving power. • The lower limit can be brought down using ultra microscope & electron microscope.
- 22. • Optical microscopy method is used to determine: a) Particle size analysis in suspensions b) Globule size distribution in emulsions c) Particle size analysis in aerosols Method: • Eye piece of the microscope is fitted with a micrometer. • This eye-piece micrometer is calibrated using a standard stage micrometer. • Take the powder sample & prepare a suspension with a suitable vehicle such as paraffin oil. • The suspension is mounted on a slide or a ruled cell & placed it on the mechanical stage.
- 23. • The suspension is mounted on a slide or a ruled cell & placed it on the mechanical stage. • The size of the particle is estimated with the help of the eye- piece micrometer. • Around 625 particles must be counted in order to estimate the true mean. • This is necessary because particles are not spherical & assessment will be subjective & inaccurate, unless a large sample is measured. • The size frequency distribution curves such as normal, log- normal, cumulative frequency & probability curves are plotted. • Finally, the statistical diameters for the powder are estimated.
- 24. Advantages • One can view particles • Any aggregates detected • Contamination of particles detected • Use of cover slip for arresting motion of particles • Easy and simple Disadvantages • Length and breadth can be detected but depth or thickness of particles cannot be measured • Slow- time consuming , tedious, inaccurate • Number of particles to be measured is more • Large sample required
- 25. 2. Sieving Method • Particles having size range between 50 & 1500µm are estimated by sieving method. • In this method, the size is expressed as dsieve, which describes the diameter of a sphere that passes through the sieve aperture as the asymmetric particle. • This method directly gives weight distribution. • Sieves for pharmaceutical testing are constructed from wire cloth with square meshes, woven from wire of brass, bronze, stainless steel or any other suitable material. • Sieves should not be coated or plated. • There must be no reaction between the material of the sieve & the substance to be sieved.
- 26. Method: • Standard sieves of different mesh numbers are available commercially as per the specifications of I.P. & U.S.P. • Sieves are arranged in a nest with the coarsest at the top sieve. • This sieves set is fixed to the mechanical shaker apparatus & shaken for a certain period of time (20 min). • The powder retained on each sieve is weighed. • Frequently , the powder is assigned the mesh number of the screen through which it passes or on which it is retained. • It is expressed in terms of arithmetic or geometric mean of the two sieves. • This is reported as undersize.
- 28. Advantage: • It is inexpensive, simple, & rapid with reproducible result. Disadvantage: • lower limit of the particle size is 50µm. • If powder is not dry, apertures become clogged with particles, leading to improper sieving. • During shaking, attrition (particles colliding with each other) occurs causing size reduction of particles. • This leads to errors in estimation.
- 29. 3. Sedimentation Method • Sedimentation method may be used over a size range of 1 to 200µm. • In this method, size is expressed as Stokes diameter, dst, which describes the diameter of as equivalent sphere having the same rate of sedimentation as that of the asymmetric particle. • Sedimentation of particles may be evaluated by different methods. Andresen pipette method, Balance method & Hydrometer method. • Sedimentation method finds applications in: – Formulation & evaluation of suspension – Formulation & evaluation of emulsions – Determination of molecular weight of polymers
- 30. Andresen Pipette Method • Method: • The Andresen apparatus is usually consists of a 550ml cylindrical vessel containing a 10ml pipette sealed to a ground glass stopper. • When the pipette is placed in the cylinder, its lower tip is 20 cm below the surface of the suspension. • Procedure: • Prepare 1 or 2% suspension of the powder in a suitable medium. • A deflocculating agent will help in uniform dispersion of the suspension. • Transfer the suspension in to the Andresen vessel. • Place the stopper & shake the vessel todistribute the suspension uniformly.
- 31. • Remove the stopper & place the two-way pipette & securely suspend the vessel in a constant temperature water bath. • At different time intervals, 10 ml samples are withdrawn using two way stopcock & collected in a watch-glass. • Samples are evaporated & weighed. • The weight or amount of particles obtained in each time interval is referred to as weight undersize. • The weights are converted in to cumulative weight undersize. • Particles diameter is calculated from stokes’ law, with ‘h’ in equation being the height of the liquid above the lower end of the pipette at the time of withdrawing the samples.
- 32. 4. Conductivity Method • Particle size ranging from 0.5 to 500µm is measured by conductivity method. • This method gives number distribution. • In fact, particle volume is measured & converted in to particle diameter. • There are various subtypes. Two popular methods are- 1 Electrical stream sensing zone method (Coulter counter Method ) 2 Laser light scattering methods • Coulter counter is used to measure the particle volume. • Thus, in this method, size is expressed as volume diameter, dv, which describes the diameter of the sphere having the same volume as that of the asymmetric particle. • This is a quick & accurate method, but the instrument is expensive.
- 33. • This method finds the application in the study of – Particle growth in suspensions & emulsions. – Dissolution of drugs in a desired medium, & – Effect of antibacterial agent on the growth of microorganism. Principle and Method: • Particles are suspended in a conducting electrolyte (say sodium chloride). • This dispersion is filled in the sample cell , that has an orifice & maintains contact with the external medium. • Electrodes are placed in the solution (inside the cell) & suspension (outside as shown in figure). • A constant voltage is applied across the two electrodes. • In this position current passes.
- 34. • When a suspended particles travel through the orifice,it displace its own volume of electrolyte in to the beaker. • The net result is a change in electrical resistance. • This change in electric resistance is termed as voltage pulse, which is related to the particle volume. • This voltage pulse is amplified & fed to a pulse height analyzer. • This analyzer is previously calibrated in terms of particle size for different threshold settings. • For a given threshold value, the pulses are electronically counted. • By changing threshold settings gradually, number of particles of each size range is obtained. • Thus the particle size distribution can be obtained. • Conductivity method is also known as stream scanning, i.e., a fluid suspension of particles passes through a sensing zone, in which individual particles are electronically sized, counted & tabulated.
- 35. coulter counter apparatusAdvantages: Using coulter counter apparatus, approximately 4000 particles per second can be counted. Therefore size distribution analysis can be completed in a relatively short period of time. It gives reasonably accurate results. Disadvantage: This method may be unsuitable for polar and highly water soluble material due to salvation. In such cases, if a nonsolvent is used to suspend the particles, it may produce adequate conductance.
- 36. Derived Properties of Powder • A few application are given below: Porosity: influence the dissolution of the drug. Bulkdensity: help in selecting container for packaging a dosage form Flow Properties: help in maintaining a uniform weight of tablets or capsules during production. Density of powders (a) bulk density (b)tapped density (c) granular density (d)true density Flow properties of powders Porosity Bulkiness
- 37. Bulk Density • Bulk density(ρ) = mass of a powder (w) / bulk volume (Vb) • When particles are packed loosely, lots of gaps between particles are observed. • Hence bulk volume increases making the powder light. Based on bulk volume, powders are classified as ‘light’ & ‘heavy’. • Light powders have high bulk volume. • Heavy powders have low bulk volume • The bulk density depends on particle size distribution, shape & cohesiveness of particles.
- 38. Method: • A powder (about 60gm) is passed through a standard sieve No. 20. • A weight amount (about 50gm) is introduced into a 100ml graduated cylinder. • The cylinder is fixed on the bulk density apparatus & the timer knob is set (regulator) for100 another 50 taps may be continued & the final volume is noted. • Further, another 50 taps may be continued & the final volume is noted. • For reproducible results, the process of tapings may be continued until concurrent volume is achieved. • This final volume is the bulk volume. • Then bulk density is calculated using equation. • Bulk volume is also measured by dropping the cylinder (containing powder) onto a hard wooden surface 3 times from a height of 1 inch at 2 seconds intervals. • Sometimes, to get an appropriate volume, the container has to be dropped or tapped 500 times.
- 39. Granule Density • Granule density is determined for thegranules that are employed in the manufacture of tablets. • Granule Density = granule weight / granule volume • Thevolume of granules can be measured bymercury displacement method. • Mercury is suitable because it fills the voids but fails to penetrate the internal pores of the particles. • The use of mercury is also based on its high contact angle of about 140° & its non wetting characteristics. • Granule volume is related to weight of the mercury that is displaced by the granules in pycnometer. • This method is as same as that reported in the liquid displacement method.
- 40. True Density • True Density = Weight of powder / True volume of powder • True Density Determination Helium displacement method (for porous powders) Liquid displacement method (for non porous powders) flotation in a liquid Porous solids – Helium displacement method:-
- 41. • Helium pycnometer consists of a sample holder(A), which can be sealed after placing the sample. • The valve(B) is connected to the sample holder. • It has provisions for removing the air from the sample holder & introducing the helium gas. • Helium gas is selected as it does not adsorb on the solid sample. • A pressure detector(C) is include in order to maintains the electric contact at a particular pressure . • A piston (D) is attached in order to read the corresponding pressure, which is also related to the volume of the powder • Initially the volume of pycnometer is determined. • The air present in the sample holder is removed by applying vacuum. • Then, helium gas is passed in to the apparatus through the valve(B).
- 42. • The pressure is adjusted & set a particular valve with the help of a movable piston(D). • At this piston, the reading on the scale denotes U1, this represents the volume of empty cell. • In the next step, pycnometer is calibrated by placing a standard sample of known true volume (Vc) (Stainless steel spheres) in the sample holder. • The sample holder is sealed & air is removed. • The same amount of the helium gas is introduced. • Pressure is adjusted to present valve by moving the piston suitably. • At this stage, the scale reading is denoted by U2. • The difference between U1 & U2 gives the volume occupied by the sphere. • The last step involves the determination of volume of the sample.
- 43. • The stainless steelsphere is replace by the test sample powder. • The air in the pycnometer is replace by the helium gas. • The pressure is adjusted with the help of piston. • At this state, the piston reading is denoted by Us. • The difference between U1 & Us gives the volume occupied by the sample. Vstd = True volume of std. sample Vtest = true volume of the test sample U1- U2 = Volume occupied by the std. sample U1- Us = Volume occupied by the test sample Vtest = Vstd *(U1- Us ) U1- U2
- 44. Liquid Displacement Method • Liquids such as water & ethyl alcohol can not occupy the pores & cervices. • If the powder is nonporous, this method is used. • Select a solvent in which the powder is insoluble & heavy. • Normally, the values obtained are somewhat lower than the helium displacement method. Pycnometer or specific gravity bottle may be used. Weight of pycnometer = w1 Weight of pycnometer + Sample(or glass beads) = w2 Weight of Sample = w3 = w2 – w1 Weight of pycnometer with powder & filled with solvent = w4 Weight of the liquid displaced by solids = w4 – w2 True Density = w2 – w1 / w4 – w2 .
- 45. Porosity True volume = Volume of the powder itself. Granule volume = Volume of the powder itself + Volume of intra particle spaces (represented by pores & cervices.) Bulk volume = Volume of the powder itself + Volume of intra particle spaces + Volume of inter particles spaces (voids.) • If the powder is nonporous i.e., no internal pores or capillary spaces, the bulk volume consists of true volume plus the volume of spaces between the particles, i.e., void volume. • Void volume( V) = Bulk volume – True volume • Porosity definition: It is the ratio of the volume of voids between particles, plus the volume of pores, to the total volume occupied by the powder, including voids and pores. • Porosity = Void volume / Bulk Volume Intra particle porosity Inter particle porosity
- 46. Flow properties of powders • Irregular flow of powder from the hopper produces tablets with non uniform weights. • As a result, content uniformity & dose precision can not be achieved in the production of tablets & capsules. • Flow properties depends on the particle size, shape, porosity & density of the bulk powder. These factors are enumerated here. • Particle size • Nature of particles • Moisture content • Angle of repose • Dispersibility • Carr’s Index • Compression Properties
- 47. Angle of Repose • The flow characteristics are measured by angle of repose. • Improper flow of powder is due to frictional forces between the particles. • These frictional forces are quantified by angle of repose. • Angle of repose is defined as the maximum angle possible between the surface of a pile of the powder & the horizontal plane. tan Ө = h / r Angle of Repose Flow < 25 Excellent 25-30 Good 30-40 Passable >40 Very poor
- 48. 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 measure. • Carr’s index (%)= Tapped density- Poured or bulk density X 100 Tapped density Flow description % Compressibility Excellent flow 5 – 15 Good 16 – 18 Fair 19 – 21 Poor 22 – 35 Very Poor 36 -40 Extremely poor > 40
- 49. Dispersibility • Dispersibility of a powder is the ability of a material to flow or pour easily over a plane. • Dispersibility, dustiness & floodability are inter-related terms. • Dispersibility(%) = Weight of powder in watch glass / initial × 100 weight of the sample Hausner’s ratio • Hausner’s ratio = tapped density/ Bulk density • Value greater than 1.5 indicates poor flow (= 33% Carr’s Compressibility Index). • More cohesive, less free-flowing powders such as flakes. • Between 1.25 and 1.5 added glidant normally improves flow. • > 1.5 added glidant doesn’t improve flow.
- 50. Compression properties: • Powders are normally compressedin to tablets using a pressure of about 5.0 kg/cm2. • This process is called compaction or compression. • During this process, the porosity of powder will changes. • Normally compacts exhibit low porosities than the powder, which is tapped in to close packing. • These substances are considered as plastic, i.e., deformed on compression. For example, soft & spongy particles such as kaolin exhibit plastic behavior. • Some substances when compacted exhibit higher porosities than that of powder in close packing. • Such materials are considered as dilatants. i.e., they show unexpected expansion under the influence of stress.