Particle Size Analysis 1 KAUSAR AHMAD KULLIYYAH OF

Particle Size Analysis 1 KAUSAR AHMAD KULLIYYAH OF PHARMACY http: //staff. iiu. edu. my/akausar PHM 3133 Dosage Design 1 2010/11

Contents 2 �Types of methods �Factors influencing selection of methods PHM 3133 Dosage Design 1 2010/11

Fundamental knowledge 3 molecules become particles become granules PHM 3133 Dosage Design 1 2010/11 become tablets etc

Process requirements 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 microencapsulation. PHM 3133 Dosage Design 1 2010/11

Examples of particle-related advances 5 � use of cholesteric liquid crystals and custom microencapsulation technologies in the personal care industry… www. hallcrest. com/about � microencapsulation technology to deliver omega-3 oils and other ingredients into functional foods. . www. ocean-nutrition. com/inside. asp? cm. Page. ID PHM 3133 Dosage Design 1 2010/11

6 http: //www. swri. org/3 pubs/brochure/d 01/microen. htm PHM 3133 Dosage Design 1 2010/11

Interactions between materials and processes 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 Ø to prepare the right material for the expected function PHM 3133 Dosage Design 1 2010/11

Example 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? PHM 3133 Dosage Design 1 2010/11

How to determine spec of cloth? 9 � Filter cloth is used to trap dust � Pore size of cloth must be smaller than dust Ø Hence, must know size of fines!! Ø To control processes IN manufacturing, need to know size of raw materials, in-process materials and finished goods. PHM 3133 Dosage Design 1 2010/11

Size distribution of products & fines 10 � How to detect the size of a sample that contains Products? ………………. normal distribution Fines? . . normal distribution Products + fines? . . . SKEWED PHM 3133 Dosage Design 1 2010/11

What method to choose? 11 Can sieving be used? Must consider screen size…. Coulter counter? Size range for a particular aperture? Microscopy? Magnification? Limitation? PHM 3133 Dosage Design 1 2010/11

Sample with wide size distribution 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? PHM 3133 Dosage Design 1 2010/11

What to analyse? 13 Powders Granules Liquids Emulsions Creams Suspensions/dispersions PHM 3133 Dosage Design 1 2010/11

Powder samples 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 PHM 3133 Dosage Design 1 2010/11

Emulsion samples 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? PHM 3133 Dosage Design 1 2010/11

Dimensions 16 � Diameter Most of the time not actual diameter BUT equivalent diameter Mean Mode � Size distribution Normal Skewed � Polydispersity � Particle shape � Statistics PHM 3133 Dosage Design 1 2010/11

Availability and cost 17 Cheap Sieves � Moderate Light microscopy Coulter counter Laser diffraction Sedimentation PHM 3133 Dosage Design 1 2010/11 Expensive Electron microscopy Light scattering Laser microscopy

Sieves 18 Suitable for: �Powder �Slurry �Dispersion �Right sieves with appropriate size interval PHM 3133 Dosage Design 1 2010/11

Laser diffraction 19 Suitable for: �Powder �Diluted liquid �Concentrated liquid? �Right lens and parameters e. g. density PHM 3133 Dosage Design 1 2010/11

Microscopy 20 �Almost all types of samples �Depends on type of microscopy �Depends on magnification �Sample preparation is important PHM 3133 Dosage Design 1 2010/11

Light microscope 21 Salicylic acid 10 X PHM 3133 Dosage Design 1 2010/11 Salicylic acid 40 X

Light microscope 22 O/W emulsion 10 X PHM 3133 Dosage Design 1 2010/11 O/W emulsion 40 X

Salicylic acid 100 X 23 coalescence PHM 3133 Dosage Design 1 2010/11

Selecting instrument 24 Need to consider: �allowable range of sizes �width & shape of the particle size distribution of sample PHM 3133 Dosage Design 1 2010/11

Sample Silica gel: 5 -300 um Granules: ave. 200 um Aspirin, grounded Technique 25 Light microscopy: mag? SEM: mag? TEM: mag? Eye cream Calamine-Zn. O lotion Polystyrene dispersion Sieves: size? Laser diffraction: lens? Viscosity Microemulsion of cod oil Colloidal sulfur Bentonite clay dispersion Photon correlation Coulter counter: aperture? Polarised light microscopy: mag? Surfactant Atomic Force Microscopy PHM 3133 Dosage Design 1 2010/11

Sizing technique for sulfur? 26 Hint: How many types of sulfur preparation available? PHM 3133 Dosage Design 1 2010/11

References 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. PHM 3133 Dosage Design 1 2010/11