particle size analysis

KAUSAR AHMADKULLIYYAH OF PHARMACY

PHM3133 Dosage Design 1 2010/11

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Particle Size Analysis

http://staff.iiu.edu.my/akausar

http://staff.iiu.edu.my/akausar

Contents


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Types of methods

Factors influencing selection of methods

Fundamental knowledge


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molecules become particles

particles become granules

granules become tablets etc

Process requirements


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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.

Examples of particle-related advances


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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?cmPageID

http://www.hallcrest.com/about

http://www.ocean-nutrition.com/inside.asp?cmPageID


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http://www.swri.org/3pubs/brochure/d01/microen/microen.htm

http://www.swri.org/3pubs/brochure/d01/microen/microen.htm

Interactions between materials and processes


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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

Example


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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?

How to determine spec of cloth?


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Filter cloth is used to trap dustPore size of cloth must be smaller than dust

Hence, must know size of fines!! To control processes IN manufacturing, need to

knowsize of raw materials, in-process materials and finished goods.

Size distribution of products & fines


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How to detect the size of a sample that contains

Products? ………………. normal distribution

Fines?....................................normal distribution

Products + fines?..............SKEWED

What method to choose?


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Can sieving be used? Must consider screen size….

Coulter counter? Size range for a particular aperture?

Microscopy? Magnification? Limitation?

Sample with wide size distribution


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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?

What to analyse?


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Powders Granules Liquids Emulsions Creams Suspensions/dispersions

Powder samples


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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

Emulsion samples


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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?

Dimensions


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Diameter Most of the time not actual diameter BUT

equivalent diameter Mean Mode

Size distribution Normal Skewed

PolydispersityParticle shapeStatistics

Availability and cost


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Cheap

Sieves

Moderate

Light microscopy

Coulter counter

Laser diffraction

Sedimentation

Expensive

Electron microscopy

Light scattering

Laser microscopy

Sieves


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Suitable for:

Powder

Slurry

Dispersion

Right sieves with appropriate size interval

Laser diffraction


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Suitable for:

Powder

Diluted liquid

Concentrated liquid?

Right lens and parameters e.g. density

Microscopy


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Almost all types of samples

Depends on type of microscopy

Depends on magnification

Sample preparation is important

Salicylic acid 10X Salicylic acid 40X


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Light microscope

O/W emulsion 10X O/W emulsion 40X


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Light microscope

Salicylic acid 100X


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coalescence

Selecting instrument


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Need to consider:

allowable range of sizes

width & shape of the particle size distribution of sample

Sample Technique

Silica gel: 5-300 um Light microscopy: mag?

Granules: ave. 200 um SEM: mag?

Aspirin, grounded TEM: mag?

Eye cream Sieves: size?

Calamine-ZnO lotion Laser diffraction: lens?

Polystyrene dispersion Viscosity

Microemulsion of cod oil Photon correlation

Colloidal sulfur Coulter counter: aperture?

Bentonite clay dispersion

Polarised light microscopy: mag?

Surfactant Atomic Force Microscopy


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Sizing technique for sulfur?


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Hint: How many types of sulfur preparation available?

References


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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 (3rd ed.). Philadelphia: Lea & Febiger.

particle size analysis

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