particle size analysis with various methods

Particle size analysis

1. PARTICLE SIZE ANALYSIS

2. By Dr Mubasheera Fathima Pg scholar Ilmul Saidla Under the guidance Of Dr Hamiduddin H.O.D Dept of Ilmul Saidla

3. Definition How do we define particle size Y Particle Size Important Necessity In Pharmaceutical Industry Methods of analysis Instruments used Particle Size In Unani Medicine Conclusion References Content

4. It is the science & technology of small particles The unit of particle size used is micrometer ( μ m), micron ( μ ) & its equal to 10 -6 m As particle size decreases, area increases. The particle size of a drug can affect its release from dosage forms that are administered orally, parenterally & topically . Micromeritics

5. Defined as being a discrete sub portion of a substance It includes solid particles , liquid droplets or gas bubbles with physical dimension ranging from sub – nanometer to several millimeters in size Common types of materials consisting of particles are Powders & granules Suspension , emulsions & slurries Aerosols & sprays Definition

6. Particles are 3 dimensional object unless they are perfect spheres , they cannot be fully described by a single dimension such as radius / diameter. A solid particle is often considered to approximate to a sphere which then can be characterized by determining the diameter of that sphere ( here hypothetical sphere – which represents only an approximation to the true size & shape of particle ) = this dimension is referred as equivalent diameter of the particle . How we define particle size

7. The particle size distribution in a powder may be quantified by Determining the number of particles – microscopy Determining the weight of the particles- sieving, sedimentation, elutriation Determining the volume of particles- coulter counter method Determining light scattering by particles – dynamic and light scattering method Particle size determination

8. Schematic representation of lifetime of a drug

9. Particle size has a direct influence on material properties such as Reactivity – Dissolution rate e.g. : catalyst , tablet Stability in suspension e.g. : sediments Efficacy of delivery e.g. : asthma inhalers Texture & feel e.g. : food ingredients Flowability & handling e.g. : granules Viscosity e.g. : nasal sprays Importance of Particle size

10. Microscopic method Optical microscopy Electron microscopy Electrical steam sensing zone method Sieve method Laser light scattering method Sedimentation methods Methods of analysis of particle size

11. There are 2 types of method Optical microscopy & electron microscopy Range 0.2 – 100 At least 300 – 500 particles must be counted Method A dilute suspension of powder is prepared in a liquid in which it is insoluble A drop of suspension is mounted on slide Observed under microscope ( eyepiece is filled with micrometer) Microscopic method

12. For ease in counting – Fluid viewed is projected on screen or photographed for later measurement. Data scientifically represented as size –frequency distribution curve From the data average particle size & size distribution is determined. For very small particles , microscope or scanning electron microscope may be used.

13. Alternatives to light microscopy includes Scanning electron microscopy (SEM) & Transmission electron microscopy (TEM) For submicron particles it is necessary to use either TEM /SEM TEM ( 0.001 – 5 micrometer ). SEM is particularly appropriate when a three dimensional particle image is required

14. Advantages Agglomerates or contamination can be detected Disadvantages Slow & boring method The measured diameter is 2 dimension only (length & breadth) , i.e. depth is not obtained

15. Sieving method Sieving method is an ordinary & simple method In this method a series of standard sieves are used, placed on a mechanical shaker Sieve of largest aperture on the top followed by sieves of gradually decreasing pore size This technique is generally used for coarse particles, more than 50 micrometer in size.

16. Method The powder whose particle size is to determined is placed on the nest of sieves The powder is shaken for a definite time The powder retained on sieve is collected & weighed The data obtained is analyzed & particle size is determined

17. Particle size of the drug plays a major role in the dissolution rate of the drugs. Almost all the formulations are prepared by powder drugs. Attiba have also mentioned the size of mesh to confirm the particle size like 40, 60, 80, 100 number of meshes (Said, 1997) which were also used by westerners in 20th Century A.D. but now the method is obsolete and „British Standard of sieve size 410: 1986‟is in vogue. The old method represents the number of openings per linear inch of mesh. But the British Pharmacopoeia defined in terms of particle size as determined by microscopy . The following terms are used: Coarse powder : All the particles of powder pass through a sieve with a nominal mesh aperture of 1700 micrometers. Moderately coarse powder : All the particles of powder pass through a sieve with a nominal mesh aperture of 710 micrometers. Moderately fine powder : All the particles of powder pass through a sieve with a nominal mesh aperture of 335 micrometers. Fine powder : All the particles of powder pass through a sieve with a nominal mesh aperture of 180 micrometers. Very fine powder : All the particles of powder pass through a sieve with a nominal mesh aperture of 125 micrometers. Micro fine powder : All the particles of powder pass through a sieve with a nominal mesh aperture of 45 micrometers. Superfine powder : All the particles of powder pass through a sieve with a nominal mesh aperture of 10 micrometers

18. Advantages Simple & inexpensive method Disadvantages Particles below 50 micrometer difficult to measure Chances of clogging of sieve Chances of attrition during sieving Need of large amount of powder

19. Coulter counter method Used for measuring particle volume The coulter counter determines the particle volume , distribution of materials suspended in an electrolyte containing solution. This instrument utilizes an electrical sensing zone & measures electrical impulses caused by passage of particles through zone. Electron stream sensing zone method

20. Method

21. Advantages It is one of the precise & accurate method Measures the size distribution of particles suspended in either liquid / gases Analysis range is wide Disadvantages Aggregation of particle produce wrong result Coarse particles blocking orifice

22. Laser light scattering method Dynamic light scattering method It determines Brownian motion ( random movement of particles) Smaller particles move / diffuse more quickly Larger particles move / diffuse More slowly Both the large particle & small particle analyzers are based on the interaction of laser light with particles.

23. Principle Laser light falls on a particle & diffraction occurs Laser diffraction measures particle size distribution by measuring the angular variation in intensity of light scattered as a laser beam passes through a dispersed particulate sample.( bcoz the angle & intensity of the scattered light depends on its size ) He Ne laser operating at 632.8nm is used larger particles scatter light at smaller angle & smaller particles scatter light at larger angles The angular scattering intensity data is then analyzed to calculate the size of the particles responsible for creating the scattering pattern using the Mie theory of light scattering

24. Surface of particle produces an electro magnetic field due to the presence of electrons & since light represents an electromagnetic radiation it can interact to produce a phenomenon that is described as mie scattering or diffraction. Mie theory embraces all possible ratios of the particle radius to wavelength. The particle size is reported as a volume equivalent sphere diameter

25. Sedimentation method Andreasen pipette method The apparatus consists of a 550ml cylindrical vessel about 5.5cm internal diameter Scale indicated from 0- 20cm Pipette is located centrally in the cylinder & is held in position by a ground –glass stopper so that its tip coincides with zero level. A two way tap allows fluid to be drawn into a 10ml reservoir , which can be emptied into a beaker or centrifuge tube.

26. Method 1 or 2 % suspension of the powder is prepared The suspension is introduced into vessel up to 550ml Vessel is stoppered & shaken Pipette is then placed & vessel is kept undisturbed at a constant temperature At various intervals , 10ml samples of suspension are withdrawn through two way stop clock Samples are placed in a previously weighed China – dishes Samples are evaporated & weighed The particle diameter at various time periods is calculated using strokes equation.

27. Advantages Simple & inexpensive The result obtained are precise Disadvantages Method is laborious – separate analysis for each sample Very small particles cannot be determined

28. Range of analysis Microscopic method – 0.2-100 micrometer Sieving method - 50-1500 micrometer Andreason pipette method - 1-200 micrometer Coulter counter method - 0.1-1000micrometer Laser light diffraction method - 30nm -1mm (1nm = 0.001micrometer ) 0.001-1000micrometer

29. Particle analysis by each method Microscopic method Almost all types of sample Depends of type of microscopy Depends on magnification Sieve method Right sieves with appropriate size interval Powder Slurry Dispersion Laser light diffraction method Powder Diluted liquid Concentrated liquid

30. Sedimentation method Powdered samples Dilute suspensions Electrical sensing zone method Powdered samples Dilute dispersions

31. Particle size analysis in Unani system of medicine Safoof , kohal , surma & kushta Powder is a mixture of finely divided drugs in dry form, The particle size of powders is standardized according to USP descriptive terms such as very fine , fine , moderately coarse , coarse & very coarse . In unani system of medicine where particle size is prescribed in a monographs, the specified sieve number are used to fractionate a weighed representative sample from the container. Sieving used in unani system of medicine ( chaanna ) The kushta , kohal particle size are assessed by Hydro 2000S technique. Kohal was assessed by Hydro 2000S technique & was found out that particle size of kohal was within the prescribed range that is below 100 (article)

32. Particle analyzer – Modern equipments Malvern mastersizer 3000 Mastersizer 2000 Mastersizer 3000 Mastersizer micro Hydro 2000S ( used with mastersizer 2000 ) Morphologi range Spray tec Zetasizer advance range Mastersizer range – laser diffraction particle size analyzers Particle size range from 0.01microm – 3500micrometer

33. Powders & particles are used in wide variety of fields either they can be used directly as pharmaceuticals catalyst , additives or binders while in other formulations they are used as raw ingredients. In suspension , particle size distribution effects the rate of sedimentation , which in return effects physical stability of product. In tablet dosage forms , particle size distribution effects flow property which inturns effects uniformity of product. Conclusion is measuring the particle size distribution is essential for stabilizing the quality of products. Conclusion

34. References Aulton pharmaceutics. Remington. Article (basic principles of particle size analysis ) – Dr Alan Rawle. Particle size analysis by Neha Mahajan. Article - Kushta particle size analysis.