1. Physical Pharmacy 21 Particle Size Introduction and Definitions Kausar Ahmad Kulliyyah of Pharmacy, IIUM

2. Physical Pharmacy 22 Contents Effect of particle size, shape Sampling The significance of sampling How to take a sample Definitions Particle size distribution Average Polydispersity Monomodal, bimodal, skewed

3. Physical Pharmacy 23 Effect of Particle Size Processing blendingdryingtabletting Drug delivery drug absorption in GIT rapid dissolution due to increased surface area (dc/dt=kS(Cs-C)) with small particles optimum particle size required in controlled release

4. Physical Pharmacy 24 Definitions of Particle Shape Acicular – needle-shaped Angular – sharp- edged Crystalline – geometric shape Dendritic – branched crystalline shape Fibrous – thread-like Granular equidimensional irregular shape Spherical – global shape

5. Physical Pharmacy 25 Effect of Particle Shape Particle shape influences such properties as: Flowability of powders Packing Interaction with fluids & covering power of pigments

6. Physical Pharmacy 26 Effect of Particle Shape on Size Variation between diameters increases as particles diverge more from the spherical shape. Different results from different techniques can be compared by applying shape factors and shape coefficients.

7. Physical Pharmacy 27 SEM pictures of polystyrene

8. SEM picture Al 2 O 3 Agglomerated Agglomerated Al 2 O 3 Physical Pharmacy 28

9. 9 Types of samples PowderLiquid SuspensionsEmulsions

10. Sampling of Powders Characteristics of many tons of material are assumed on the basis of analyses carried out on grams or milligrams. Bias at any stage will affect final analysis. Therefore, a sample should represent the bulk. Delivery of materials - 10 kg Gross sample - 1 kgLab sample - 1 g Measurement sample - 1 mg Physical Pharmacy 210

11. Physical Pharmacy 211 Bulk Sampling – Type of Material Non-flowing material Fine powders, sticky, moist, fibrous solids Does not segregate Surface sampling acceptable Free-flowing material Segregate especially with small particles Sampling must be done from different locations

12. Type of sampling Sampling from container Sampling from big bags Physical Pharmacy 212

13. Sampling from bag/sack/drum Inspect condition of bags Inspect condition of bags Select bags at random Select bags at random Scoop sampling is widely used method due to its simplicity. Scoop sampling is widely used method due to its simplicity. It is supposed that the powder, at the point at which the scoop is inserted, represents the bulk It is supposed that the powder, at the point at which the scoop is inserted, represents the bulk Increase accuracy by having more than one sample (CHECK how this is done @ pilot plant) Increase accuracy by having more than one sample (CHECK how this is done @ pilot plant) See http://www.kersting- ind.de/uploads/media/Pharma__UDS_engl.pdf http://www.kersting- ind.de/uploads/media/Pharma__UDS_engl.pdfhttp://www.kersting- ind.de/uploads/media/Pharma__UDS_engl.pdf Physical Pharmacy 213

14. Physical Pharmacy 214 On-line Sampling Normally taken during the process For quality control purpose/IPQC, samples should be taken only when the process has stabilised Samples taken from different sampling point e.g. on a conveying belt or screw

15. Physical Pharmacy 215 Sampling from Emulsion & Suspension Samples must be stirred before samples are taken Accuracy increases with more than one sample

16. Physical Pharmacy 216 Definitions of Particle Size Volume diameter diameter of a sphere having the same volume as the particle Surface diameter diameter of a sphere having the same surface as the particle Stoke’s diameter the free falling diameter of a particle in the laminar flow region (Re < 0.2) Sieve diameter the width of the minimum square aperture through which the particle will pass

17. Physical Pharmacy 217 Average Particle Size Number average Length average Surface area average Volume average

18. Physical Pharmacy 218 Average Diameter Volume average diameter Obtained from the Volume distribution weighted (strongly influenced) by coarse particles. Number average diameter Obtained from the Number distribution weighted to the small particles. This type of "average particle size" is related to population.

19. Physical Pharmacy 219 Example of PSD: Particles with different diameters.

20. Physical Pharmacy 220 Polydispersity Index/Span/Width Describes the variation in sizesMonodisperse particles have the same size PI close to zero Polydisperse particle have various sizes PI very big Must be defined clearly. E.g. polydispersity = d(0.9) – d(0.1)/d(0.5)

21. Physical Pharmacy 221 PSD – Perfluorocarbon emulsion Polydisperse

22. Physical Pharmacy 222 PSD - Liposome PL-PSDA (Polymer Lab: HDC mechanism) Skewed to the right

23. Physical Pharmacy 223 PSD – Colloidal silica Skewed to the left

24. Physical Pharmacy 224 PSD - PVC Latex overlay of two sample distributions High polydispersity index Almost monodisperse

25. Physical Pharmacy 225 PSD - Polystyrene Latex Blend Bimodal distribution

26. Physical Pharmacy 226 PSD - n-butyl acrylate latex overlay of sequential samples taken from reactor initial final

27. Physical Pharmacy 227 References Keishi Gotoh et al, Powder Technology Handbook 2 nd Ed., Marcel Dekker, New York (1997) Muhammad E Fayed & Lambert Otten, Handbook of Powder Science & Technology 2 nd Ed., Chapman & Hall, New York (1997) ME Aulton, Pharmaceutics: The Science of dosage form design, Churchill Livingstone, London (1988). Chap 33, p 564, p 581 http://www.polymerlabs.com/partsiz e/psdaapps.htm