powder technology I & II Flashcards
What is micrometrics?
Science and techonolgy of small particles
What does particle shape, size and SA effect?
- Physical, chemical and pharmacologic properties of drug - biological performance
- Powder flow - mixing during production/manufacturing
- Release of drug from dosage forms
- Stability of formulation (suspensions, emulsions)
What is parameter is particle size measured by?
Diammeter - this can be related by a number of aspects in equivalent spheres e.g. volume, SA
How can particle size be distributed?
Polydispersed systems form a frequency distribution curve, where distributions can be uniform, skewed or bio-modal.
Pharmaceutical powders usually form a skewed distribution.
What are the triple-point size distribution parameters?
Three point size distribution is based on the diammeters below which 90%, 50% and 10% of the particles lay.
This is expressed as X(90), D90 or D[0.90].
What is weighted distribution of particles
?
This is where a certain characteristic is used to define distribution, being;
- number weighted: each particle is evenly weighted irrespective of size.
- volume weighted: each particle contributes to the related volume of the particles
- intensity weighted: correlates to the intensity of scattered light by the particle
Particle size vaires depending on what principle is used to measure it.
Why is particle size important? What does it influence?
It is the most important physical property of powders as it effects;
- Dissolution rate (noyes-whitney) - Stability in suspension - Efficacy of delivery - Texture and feel - Appearance - Flowability and handling - Viscosity - Packing density and porosity.
How can particle size be determined? List each method.
- microscopy via Martin’s or Feret’s diammeter
- optical microscopy
- sieving
- coulter counter
- light scattering including laser diffraciton and photon correlation spectroscopy
- sedimentation
Describe Martin and Feret’s diammeter and what techniques this is involved in.
Martin’s diameter (dm): the distance between opposite sides of a particle measured on a line bisecting the projected area. To ensure statistical significance all measurements are made in the same direction regardless of particle orientation.
Feret’s diameter (df): the distance between parallel tangents on opposing sides of the particle profile.
Used in microscopy including optical, scanning electron and transmission electron. These are applied to ensure that particles are being measured in the same way.
Describe how particles are measured by sieving and not important parameters.
Particles pass through multiple sieves of decreasaing coarseness, where aperture is decreasing.
The particle size is given based on sieve diammeter, and occurs until <0.2% of material passes through a given aperture in a 5 minute interval.
Limitations are that at least 25g of material is required and sieving oily or cohesive p/owders/granules can lead to clogging of openings.
Powder size classifications can be defines using pharmacopeias.
Describe coulter counter analysis including mechanisms and practical considerations.
Coulter counter analyses powder based on change in conductivity of aperture as particles traverse - requiring a conducting liquid. The aperture refers to an opening between electrodes that senses passing of suspending particles.
Only a dilute sample is required, where suspension is drawn through a small oriface and electrodes monitor aperture change by electrical signals produced when particles occupy this oriface. Change in resistance is proportional to volume, and this change is converted to a voltage pulse that is amplified and processed electronically.
Practical considerations are:
- Tube selections: use microscope to get an idea of larget particle - Electrolyte: must conduct, not dissolve. Clean and particle free - Dispersion: need suitable concentration, wetting agent, break aggregates, representative sample - Coincidence: more than one particle at a time
