Physical Pharmacy-II (Micromeritics).pptx

B. Pharm 4th semester
Physical Pharmacy-II
Unit-4: Micromeritics Property
As per PCI syllabus

1. B.Pharm 4 th semester Physical Pharmacy-II Unit-4: Micromeritics Mr. Subhasish Pramanik Assistant Professor Mata Gujri college of Pharmacy 1

2. Micromeritics is science of small particles and the study of particle size distribution. Micromeritics is the study of a number of characteristics, including particle size and distribution, shape, angle of repose, porosity, true volume, bulk volume, apparent density, and bulkiness. The unit of particle size used most frequently is micrometer, µm or Micron ( µ)and is equal to 10 -6 m or 10 -3 mm. Sometime millimicron unit is used and is equal to 10 -9 m. The millimicron is commonly referred to as the nanometer, nm. 2 MICROMERITICS

3. 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 : Bulk density, Tapped density, Granular density and True density Flow properties of powders Porosity Bulkiness 3

4. PARTICLE SIZE Particle size is important in extraction process. When a powder sample contains of uniform size, it is said to be monodisperse. In collection of particles of more than one size, it is said to be polydisperse. The pharmaceutical powders are almost always be polydisperse and hence it is necessary to characterise particle size and their distribution. Denoted in micrometers (formerly called as microns) 1 m = 1000 mm 1 mm = 1000 µm 1 µ m = 1000 nm 4 Fundamental properties

5. Average Particle Size : An average or mean diameter is usually used for comparison of particle size of two different batches for same material. No. of Particles (n) Size of Particles (d) nd 15 50 750 25 70 1750 95 90 8550 140 110 15400 =26450 No. of Particles (n) Size of Particles (d) nd 15 50 750 25 70 1750 95 90 8550 140 110 15400 =26450/275 =96.18 µm   5

6. Particle size determination (PSD) -Methods Optical Microscopy (by size) Sieving Method (by wight) Sedimentation Method (separation method) Conductivity Method (counting method) 6

7. Optical Microscopy The optical microscopy can be used to measure the particles size in the range of 0.2 µm to 100 µm. In this method the size is expressed as projected diameter ( d p ). By this method the number distribution data can be obtained and it can be converted to weight distribution. The resolving power of optical microscope is less as compared to ultramicroscope or electron microscope. In this method, an emulsion or suspension, diluted or undiluted, is mounted on a slide or ruled cell. Eye-piece of the microscope is fitted with a micrometer, called ocular micrometer. The eyepiece micrometer is calibrated using a stage micrometer. The slide is placed on a mechanical stage. The size of particle is determined with the help of eyepiece micrometer. The field can be projected onto a screen where particles are measured more accurately and photograph can be taken. 7

8. The optical microscopy method can be used to determine the particle size analysis in suspensions, in aerosols or in emulsion (droplet size). Advantages Microscopy method allows the direct observation (shape and size) of particles. Aggregation of particles can be easily detected. Provides accurate results and reproducibility. Simple and economic. Easy to handle. Disadvantages Diameter is obtained from only two dimensions of the particle i.e., length and breadth. No estimation of depth (thickness) of particle. The method is slow, because the number of particles that must be counted (300-500) to obtain a good estimation of the distribution. Time consuming method. 8

9. 2. Sieving method Mechanical sieving is generally used for the particles having size range between 50 µm to 1500µm. It consist of a series of standard sieves calibrated by the N.B.S. [National Bureau of Standards]. This method directly gives weight distribution. Sieves are generally used for grinding coarser particles. This method is useful in the development of some dosage forms like tablets and capsules. Sieves for pharmaceutical testing are constructed from wire cloth with square meshes. Standard sieves of different mesh numbers are available commercially. The sieves are arranged in a nest of about five with the coarsest at top. 9

10. Method: A sieve stack usually comprises 6-8 sieves. Powder is loaded on to the coarsest sieve of the stack and then it is subjected to mechanical vibration for specified time. After this time, the powder retained on each sieve is weighed The particles are considered to be retained on the sieve mesh with an aperture corresponding to the sieve diameter. The size is estimated as per the standards g iven in pharmacopoeia . Advantages It is simple for handling. It is inexpensive and rapid. Provides reproducible results. Specially useful for weight distribution. 10

11. 11 Disadvantages It cannot used for very small particles is below 50 µ m. Time consuming method. The powder sample should be dried, otherwise it may clog with particles, resulting improper sieving. During shaking, attrition of particles may cause reduction of particle size. This may leads to errors in estimation.

12. 3. Sedimentation Method Particle size can be determined by examining the powder as it sediments out. O ne of the most popular of the pipette methods was that developed by Andreasen and Lundberg and commonly called the Andreasen pipette. In this method , known volumes of suspension are drawn off and the concentration differences are measured with respect to time. The sedimentation method can be used for formulation and evaluation of suspensions. emulsions and determination of molecular weight of polymers. The particle size in the subsieve range may be obtained by gravity sedimentation and is expressed as stokes' diameter, d st ' in Stokes' law. The apparatus usually consist of 550 ml vessel containing a 10 ml pipette sealed into a ground glass stopper. When the pipette is in place in the cylinder, its lower tip is 20cm below the surface of the suspension. 12

13. Method: 1 or 2% suspension of powder in a suitable medium firstly prepared and to that add suitable deflocculating agent. Transfer this mixture (suspension) into the Andreasen vessel. Shake the suspension for uniformity. Two-way pipette is placed & securely suspended in constant temperature bath. At a given intervals of time, 10 ml samples are withdrawn from a specified depth without disturbing the suspension. The amount of powder can be determined by weight following drying or centrifuging; alternatively, chemical analysis of the particles can be carried out. 13

14. The particle size is determined in terms of stokes’ diameter   : stokes diameter : viscosity of medium : sedimentation height : difference in density of particle and fluid : force of gravity : sedimentation time   14

15. Advantage: Equipment require Can be relatively simple and inexpensive Can measured a wide range of sizes with considerable accuracy an reproducibility. Disadvantage: Sedimentation analysis must be carried out at concentration, which are sufficiently low for interactive effect between particles to be negligible, so that their terminal falling velocities can be taken as equal to those of isolated particles. Large particle create turbulence are slowed and are recorded under size. Carefully temperature control is ready to suppress the convection currents. Particle re-aggregation during extended measurement. Particles have to be completely insoluble in the suspending liquid 15

16. 4. Conductivity methods The popular instrument to measure the volume of particles is the coulter counter . This method gives number distribution. Here the particle volume is measured and is converted into particle diameter, and size is expressed as volume diameter d v . The method is useful in the study of particle growth in suspension and solutions, useful in dissolution studies and to study the effect of antibacterial agents on the growth of microorganisms. This method gives a quick and accurate results. Method: Powder samples are dispersed in an electrolyte to form a very dilute suspension. The particle suspension is drawn through orifice into the wall of a hollow glass tube. Electrodes, situated on either side of the aperture are surrounded by an electrolyte solution. These electrodes monitor the change in electrical signal which occurs when a particle m omentarily occupies the orifice and displaces its own vol u me of e l e ctrolyt e . The volume of electrolyte fluid which is displaced in the orifice by the presence of a particle causes a change in electrical resistance between the electrodes which is proportional to the volume of the particle. 16

17. Advantage: Particle size ranging from 0.5 – 500 µm. Gives number distribution, Particle volume measured and can be converted to diameter. Accurate, sensitive, fast technique. 4000 particles per second can be counted. Disadvantage Expensive 17

18. 18 B. PARTICLE SHAPE DETERMINATION Particle shape also has influence on surface area, flow properties, packing and compaction of the particles. Spherical particles have minimum surface area and better flow properties. Shape can also have influence on rate of dissolution of drugs. Techniques of Particle Shape Determination 1. Microscopy method 2. Light scattering method

19. C. SURFACE AREA Surface area of a powder can be calculated using particle size data obtained from any suitable method. Specific surface area i.e. surface area per unit weight ( S w ) or unit volume ( S v ) can be estimated as follows: surface area of particles / volume of particles Surface area is an important parameter as the bioavailability of certain drugs is dependent on surface area. S urface area determination method: Adsorption method (by using Solute and by using Gas) Air-Permeability method. 19

20. 20 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 and helium gas. Once surface adsorption has reached equilibrium, the sample is heated at right temp. and Nitrogen gas is desorbed. Its volume is measured. As each N 2 mol. occupies fixed area, one can compute surface area of pre-weighed sample. Surface area is most commonly determined based on Brunauer Emmett-Teller (BET) theory of adsorption. Adsorption method

21. 21 QUINTASORB INSTRUMENT

22. 2. Air Permeability method This method is based on the principle that resistant offered to the flow of fluid (i.e. Air). Powder is packed as compact plug in sample holder. In this packing particle surface-surface contact 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. 22 Diagram of Fisher Subsieve Sizer

23. Derived properties Derived Properties depend on fundamental property and define the factors relating with their measurement. That is Density, porosity, bulkiness and Flow property. 23 Porosity The volume of space between particles may vary depending on the size, shape and density of the particles. Porosity is the measurement of air space or voids in a material. Suppose a powder is placed in a graduated cylinder and total volume noted. The volume occupied known as bulk volume ( V b ) .The bulk volume of powder consists of the true volume of solid particles plus the volume of the spaces between particles, The volume of the spaces, known as the void volume (V). V= V b -V p Where, V p = True Volume Porosity is generally expressed in percent. % of Porosity (Ɛ) = ( )X100  

24. 24 2. Densities of particles Systems of particulate solids are most complex physical systems encountered in pharmacy. Basically density is defined as weight per unit volume. Three types of densities. Bulk density II. Granule density and III. True/Tapped density. I. Bulk density, ( ρ b ) is defined as the mass of a powder divided by the bulk volume. On the basis of bulk volume, powders may be classified as, "light" and "heavy". Light powders have high bulk volume. The bulk density of a powder depends mainly on particle size distribution, particle shape .

25. 25 II. True density ( ρ t ) is the density of the actual solid material. The volume occupied by voids (inter-particle spaces) and intraparticle pores are excluded or not included in the measurement. The cylinder is subjected to fixed no. of taps on a mechanical tapper apparatus ( approx 100) until the powder bed has reached minimum. III. Granule Density ( ρ g ) is determined for the granules that are employed in the manufacture of tablets.  

26. 26 Comparison of Bulk, Granule and True density

27. 27 Applications of Density Decides the size of the capsule based on bulk and tapped volume of a given sample. Helps to decide proper size of a container or packing material. Bulk density Apparatus

28. 3. Flow properties of Powder Pharmaceutical powders may be broadly classified as free-flowing or cohesive. Most flow properties are significantly affected by changes in particle size, density, electrostatic charges, adsorbed moisture. Good flow property is required for easy and uniform flow from hopper to die cavity ensuring accurate weight and dose for tablets. Angle of repose: It is defined as the maximum angle possible between the surface of a pile of the powder and the horizontal plane. Angle of repose is calculated for estimating flow properties. 28

29. 29 Angle of Repose ( θ ) Flow Property <25 Excellent 25-30 Good 31-40 Satisfactory 41-50 Poor >51 Very Poor Where, h=Hight of the pile, r = Radius of pile.

30. 30 Percentage compressibility: Compressibility is the ability of the powder to decrease the volume under pressure. It is measured by % Carr’s Index. )X100 Hausner Ratio: it is the important parameter to measure flow property. It affects the mass of uniformity of the dose. )   Sl. No. %Carr’s Index Flow Property Hausner Ratio 1 <10 Excellent 1.00 - 1.11 2 11-15 Good 1.12 - 1.18 3 16-20 Fair 1.19 - 1.25 4 21-25 Passable 1.26 - 1.34 5 26-31 Poor 1.35 - 1.45 6 32-37 Very poor >1.45 7 >37 Extremely Poor -

31. Improving Flow Property Altering particle size increasing particle size improve the flow properties due to reduction in cohesive force. Removal of addition of fines: An optimum concentration of fines is desirable to improve flow properties. Altering the particle shape: Spherical particle have better flow property compare to irregular particle. Removing extra moisture: Drying of powder can improve the flow of powder by decreasing cohesiveness. Temperature: The cohesion of particle decrease as the temperature is decreases. 31