Particle size distribution and its methods

Particle size expression, particle size distribution, Methods for determining particle size, Calculation

1. PARTICLE SIZE DISTRIBUTION AND ITS METHODS

2. PARTICLE SIZE DISTRIBUTION AND ITS METHODS presented by MD JAHA SULTANA, M. Pharmacy (pharmaceutics) 137N1S0308. Under the Guidance of Mr. S.SELVA RAJ, M. Pharm Assistant Professor, Department of Pharmaceutics. VIJAYA INSTITUTE OF PHARMACEUTICAL SCIENCES FOR WOMEN Enikepadu, Vijayawada-521108

3. CONTENTS Introduction Particle size expression Particle size distribution Methods for determination of particle size Calculation of average particle size Conclusion

4. A particle is a small localized object through which several physical or chemical properties such as volume or mass are described. Particle size , also called grain size , refers to the diameter of individual grains of sediment. The Particle-size distribution is defines the relative amount of particles present according to size. PSD is also known as grain size distribution. INTRODUCTION

5. Spherical particles – Diameter Non spherical particles – Surface area, volume or diameter of spherical particles SIZE OF PARTICLES MAY BE EXPRESSED

6. Surface diameter (d s ): Having same surface area of asymmetric particles. Volume diameter (d v ): Having same volume of asymmetric particles. Volume - surface diameter: Having same volume to the surface area ratio of particles.

7. Sieve diameter: Passed through the sieve aperture as the particle. Stocke’s diameter: Having same density of asymmetric particles. Projected diameter: Having same observed area of asymmetric particles.

8. It is determine in two ways Microscopic technique (number) Sieving method (weight) 1. Frequency distribution curve: It is obtained by plotting a graph between number (or) weight of the particles Vs size range (or) mean particle size PARTICLE SIZE DISTRIBUTION

9. 2. Normal and Weight distribution: Due to large variation in size of powders normal distribution is not seen. Such distributions is termed as unsymmetrical or skewed . 3. Log Normal distribution curves: It is shown by powders which obtained by crystallization and milling methods. Graph is plotted against log mean particle size and % frequency.

10. 4. Cumulative frequency distribution curve: It is obtained by plotting particle size against cumulative % frequency. A sigmoid curve is obtained by plotting the data values and then joining them.

11. Microscopic method Sieving method Sedimentation method Coulter – counter method METHODS FOR DETERMINING PARTICLE SIZE

12. MICROSCOPIC METHOD

13. Optical microscopy (1-150µm) Electron microscopy ( 0.001 - 5µ) For submicron particles it is necessary to use either TEM (Transmission Electron Microscopy) or SEM (Scanning Electron Microscopy). TEM and SEM (0.001-5µm)

14. Procedure:

15. ADVANTAGES: Relatively inexpensive. Each particle individually examined - detect aggregates, 2D shape, colour, melting point etc. Small sample sizes required. DISADVANTAGES: Time consuming. High operator fatigue - few particles examined. Very low output. No information on 3D shape. MANUAL OPTICAL MICROSCOPY

16. TRANSMISSION AND SCANNING ELECTRON MICROSCOPY ADVANTAGES: Particles are individually examined. Visual means to see sub-micron specimens. Particle shape can be measured. DISADVANTAGES: Very expensive. Time consuming sample preparation. Materials such as emulsions difficult/impossible to prepare. Not for routine use.

17. SIEVING METHOD

18. This method is used for particle size having range from 50 - 1500µm. This method directly gives weight distribution . Sieve number is defined as number of pores per linear inch. Generally the pore size is ranging from 90 µm to 5 µm . Based on sieve number particles may be classified as: Passage of all particles through sieves Passage of particles not more than 40% through sieves Grade of powdered particles 10 44 Coarse 22 60 Moderately coarse 44 85 Moderately fine 85 - Fine 120 - Very fine

19. Procedure:

20. ADVANTAGES: Easy to perform. Wide size range. Inexpensive. DISADVANTAGES: Weight changes while loading and unloading. Irregular particles. Attrition occur. Labour intensive.

21. Based on sedimentation principle various methods are available for determination of particle diameter. Pipette method Balance method Hydrometer method Pipette method is most widely used because of ease of analysis, accuracy and economy. Particle size is expressed in stokes diameter ( d st ). SEDIMENTATION METHOD

22. ANDREASEN PIPETTE Construction: 10 ml Andreason pipette. 550 ml vessel. Pipette is sealed with glass stopper. The lower tip of pipette is placed 20cm below the surface of suspension. Method: 1 – 2 % o f suspension of the particles in a suitable medium is prepared and placed into the vessel. The medium should have deflocculating agents in order to separate any aggregates if present. A stopper is placed onto the vessel and shaken vigorously. The entire set up is placed in a water bath maintained at constant temperature. Each 10ml of the sample is withdrawn into a weighed china dish. Then the samples are evaporated and weighed separately.

23. The particle diameter can be determined using stoke’s equation and rate of sedimentation. Where, d = Stoke’s diameter. η 1 = Viscosity of the medium. ρ = Density of the powder. ρ 1 = Density of the medium. g = Acceleration due to gravity .

24. ADVANTAGES: Equipment is simple and inexpensive. Accurate results can be obtained if standard method is followed. DISADVANTAGES: Laborious method. Careful temperature control is necessary to suppress convection currents. Chance of re-aggregation of particles during extended measurements. Determination of smaller sized particles is inaccurate.

25. COULTER – COUNTER METHOD

26. Construction: Two electrodes : One electrode is dipped into a container containing electrolyte and particles. Other electrode is immersed in a tube containing the electrolyte solution. Tube : Holds second electrolyte. Orifice : Present between the tube and the container which connects them. Container : Contains electrolyte solution Amplifier : Electrodes are connected to amplifier through their terminals. Mercury tube : Connected to the counter drive.

27. Method:

28. Advantages: Accurate results. Less time consuming. Automatic. Volume of very small particles in the size range of 0.5 – 1000 µm can be obtained. Disadvantages: Sample has to be suspended in predetermined volume of electrolytic solution. Aggregation of particles.

29. Edmundson has given a mathematical equation for average particle size. Where, n = number of particles in each range. d = equivalent diameter p = size index f = frequency CALCULATION OF AVERAGE PARTICLE SIZE

30. Examples: Drug Particle Size Requirement Hydrocortisone (o/w) 90% of the particles should be in the range of 5 – 50 µm Insulin Zinc amorphous form (Injection) < 2 µm Betamethasone (tablets) 90% of the particles should be < 5 µm

31. Powders and particles are used in a wide variety of fields either they can be used directly as pharmaceuticals, catalysts, additives, or binders while in other formulations they are used as raw ingredients. In both the cases, particle size distribution have major effects on performance and quality of a final product. In suspension, particle size distribution effects the rate of sedimentation, which inturn effects physical stability of the product. In tablets dosage forms, particle size distribution effects flow property which inturn effects uniformity of product. So from this, I conclude that measuring the particle size distribution is essential for stabilizing the quality of products. CONCULSION

32. Alfred Martin; A text book of Physical Pharmacy; fifth edition ; Page No: 533-546. Aultons ; Pharmaceutics The Design & Manufacture of Medicines; third edition; Page No: 121-135. Manavalan . Ramasamy; Physical Pharmaceutics; Page No: 313-326. D.V.Derle ; Essentials of physical pharmacy; Page No:182-194. Cooper and Gunn’s; Tutorial pharmacy;Page No:174-182 . en.wikipedia.org/wiki/Particle- sizedistribution www.horiba.com/fileadmin/uploads/.../PSA/PSA_Guidebook.pdf www.inventi.in/Article/ppt/587/12.aspx www.tcd.ie/CMA/misc/particle.ppt‎ terpconnect.umd.edu/~sehrman/particle-class/PSA-05-1-and2.ppt‎ http://www.authorstream.com/Presentation/javadsameni-231114-particle-size-analysis-pharmaceutics-particles-science-technology-ppt-powerpoint/ www.rci.rutgers.edu/~moghe/PSD%20Basics.pdf REFERENCE