1. KAUSAR AHMAD KULLIYYAH OF PHARMACY PHM3133 Dosage Design 1 2010/11 1 Particle Size Analysis http://staff.iiu.edu.my/akausar

2. Contents PHM3133 Dosage Design 1 2010/11 2 Types of methods Factors influencing selection of methods

3. Fundamental knowledge PHM3133 Dosage Design 1 2010/11 3 molecules become particles particles become granules granules become tablets etc

4. Process requirements PHM3133 Dosage Design 1 2010/11 4 From crystallization to formulation formation of particles drying granulation mixing compression dissolution Specific operations dehydration/impregnation, spherical crystallization and the series of operations involved in micro- encapsulation.

5. Examples of particle-related advances PHM3133 Dosage Design 1 2010/11 5 use of cholesteric liquid crystals and custom microencapsulation technologies in the personal care industry… www.hallcrest.com/aboutwww.hallcrest.com/about microencapsulation technology to deliver omega-3 oils and other ingredients into functional foods.... www.ocean-nutrition.com/inside.asp?cmPageID www.ocean-nutrition.com/inside.asp?cmPageID

6. PHM3133 Dosage Design 1 2010/11 6 http://www.swri.org/3pubs/brochure/d01/microen/microen.htm

7. Interactions between materials and processes PHM3133 Dosage Design 1 2010/11 7 Influenced by particle size Need to choose correct scale of observation e.g.right sizing method appropriate parameters e.g. right aperture, lens, medium right measurements e.g. calibrated, good quality standards to prepare the right material for the expected function

8. Example PHM3133 Dosage Design 1 2010/11 8 After size reduction, lots of fines were generated because of bad process condition. To separate fines from product, a series of cyclones were used. Eventually, the fines must be trapped using a dust filter. WHAT IS THE SPECIFICATION of the filter cloth?

9. How to determine spec of cloth? PHM3133 Dosage Design 1 2010/11 9 Filter cloth is used to trap dust Pore size of cloth must be smaller than dust Hence, must know size of fines!! To control processes IN manufacturing, need to know size of raw materials, in-process materials and finished goods.

10. Size distribution of products & fines PHM3133 Dosage Design 1 2010/11 10 How to detect the size of a sample that contains Products? ………………. normal distribution Fines?.................................... normal distribution Products + fines?.............. SKEWED

11. What method to choose? PHM3133 Dosage Design 1 2010/11 11 Can sieving be used? Must consider screen size…. Coulter counter? Size range for a particular aperture? Microscopy? Magnification? Limitation?

12. Sample with wide size distribution PHM3133 Dosage Design 1 2010/11 12 Not desirable as a product Rate of dissolution differs Processing problem Fines tend to agglomerate Fines may affect flow Measurements must be carried out more than once Coulter counter - at least two apertures Exercise: how about laser diffraction?

13. What to analyse? PHM3133 Dosage Design 1 2010/11 13 Powders Granules Liquids Emulsions Creams Suspensions/dispersions

14. Powder samples PHM3133 Dosage Design 1 2010/11 14 Flowability/dispersibility Poor if too fine. Why? Exercise: how to counter this problem when using Coulter? Shape Crystalline – geometric shape Acicular – needle-shape Granular equidimensional irregular shape Spherical

15. Emulsion samples PHM3133 Dosage Design 1 2010/11 15 Will the size change upon dilution? Can you use Coulter principle to measure size of fine sugar? Will there be changes in zeta potential that may affect stability? Can the technique employed analyse neat sample?

16. Dimensions PHM3133 Dosage Design 1 2010/11 16 Diameter Most of the time not actual diameter BUT equivalent diameter Mean Mode Size distribution Normal Skewed Polydispersity Particle shape Statistics

17. Availability and cost PHM3133 Dosage Design 1 2010/11 17 Cheap Sieves Moderate Light microscopy Coulter counter Laser diffraction Sedimentation Expensive Electron microscopy Light scattering Laser microscopy

18. Sieves PHM3133 Dosage Design 1 2010/11 18 Suitable for: Powder Slurry Dispersion Right sieves with appropriate size interval

19. Laser diffraction PHM3133 Dosage Design 1 2010/11 19 Suitable for: Powder Diluted liquid Concentrated liquid? Right lens and parameters e.g. density

20. Microscopy PHM3133 Dosage Design 1 2010/11 20 Almost all types of samples Depends on type of microscopy Depends on magnification Sample preparation is important

21. Salicylic acid 10X Salicylic acid 40X PHM3133 Dosage Design 1 2010/11 21 Light microscope

22. O/W emulsion 10X O/W emulsion 40X PHM3133 Dosage Design 1 2010/11 22 Light microscope

23. Salicylic acid 100X PHM3133 Dosage Design 1 2010/11 23 coalescence

24. Selecting instrument PHM3133 Dosage Design 1 2010/11 24 Need to consider: allowable range of sizes width & shape of the particle size distribution of sample

25. SampleTechnique Silica gel: 5-300 umLight microscopy: mag? Granules: ave. 200 umSEM: mag? Aspirin, groundedTEM: mag? Eye creamSieves: size? Calamine-ZnO lotionLaser diffraction: lens? Polystyrene dispersionViscosity Microemulsion of cod oilPhoton correlation Colloidal sulfurCoulter counter: aperture? Bentonite clay dispersionPolarised light microscopy: mag? SurfactantAtomic Force Microscopy PHM3133 Dosage Design 1 2010/11 25

26. Sizing technique for sulfur? PHM3133 Dosage Design 1 2010/11 26 Hint: How many types of sulfur preparation available?

27. References PHM3133 Dosage Design 1 2010/11 27 Aulton, M. E. (1988). Pharmaceutics: The Science of dosage form design. London: Churchill Livingstone. Llachman, L, Lieberman, H. A. and Kanig, J. L. (1986). The theory and practice of industrial pharmacy (3 rd ed.). Philadelphia: Lea & Febiger.