partical size analysis

Question 1

what is the importance of particle size reduction (what does the size and surface area affect)

Answer 1

 The rate of drug dissolution and release from dosage forms

 Flow properties of granules and powders.

 Proper mixing of granules and powders.

 Physical stability for suspensions.

 Grittiness for topical formulation (powder must beimpalpable).

 Irritation of the eyes for
ophthalmic suspensions (small
particles must be used).

Question 2

how many and what dimension do we measure when using spheres

Answer 2

1, the diameter

Question 3

what is the equivalent diameter

Answer 3

an hypothetical sphere,which represents only an approximation to the true size of the irregular particle

Question 4

give examples on different equivalent diameters

Answer 4

weight, volume, surface area, sedimentation, length, sieve diameter

Question 5

are most powders monodispered or polydispersed?

Answer 5

polydispersed (multiple diameters in the powder)

Question 6

how can we define the size distribution of a polydisperse?

Answer 6

the size distribution can be
broken down into different size ranges, which can be presented in the form of a histogram (or curve).

 The histogram presentation allows also to compare the characteristics of two or more polydisperse powder samples.

When the number (or weights) of particles lying within a certain size range is plotted against a size range (or mean particle size), a frequency distribution curve is obtained.

Question 7

what info can we take from the frequency distribution curve

Answer 7

the mode

when normally distributed
mean=median=mode

mean= average

mode= the highest frequency

median is the half

Question 8

we can plot % of particles in each size range instead

Question 9

what’s the difference between weight and number distribution?

Answer 9

number—– data collected by counting ( microscopy and coulter)

weight—- based on weight ( sedimentation and sieving)

we can convert number to weight assuming that the general shape and density of particles are independent

Question 10

how can we see if the skewed distribution is normal ?

Answer 10

by using a log- normal distribution

Question 11

what are the different distributions

Answer 11

a) Normal distribution: the mode separates the curves into two symmetrical halves.

b) Positively skewed: a frequency curve with an elongated tail towards the higher size range.

c) Negatively skewed: a frequency curve with an elongated tail towards
the lower size range.

d) Bimodal: the frequency curve containing two peaks (two modes).

Question 12

what is the cumulative frequency distribution?

Answer 12

Cumulative % oversize:
The total percent of particles
with size higher than the lower
limit of each class interval

Cumulative % undersize:
The total % of particles with size
lower than the upper limit of
each class interval

we can take the median from it, and estimate the degree of skewness

Question 13

what are the methods of particle size analysis

Answer 13

1. Sieve analysis method.
2. Microscopy.
3. Sedimentation in a liquid or gas.
4. Electrical sensing zone method
5. Laser light scattering

Question 14

what is the serving method

Answer 14

most widely used for being simple, cheap, accurate and rapid

uses different sieves, and we can find the sieve diameter from it

Question 15

how is the sieve method used

Answer 15

we usually use dry powders

we can use wet sieving for suspensions and powders that agglomerates

Sieve analysis uses wire woven stainless steel meshes
with known aperture diameters which form a physical barrier to particle

Most sieve analysis use a stack or nest of sieves which has the smallest mesh above a collector tray followed by meshes that become progressively coarser towards the top of the stack of sieves.

 The sieves are mounted on a mechanical shaker.

 Powder is loaded on to the coarsest sieve at the top of the assembled stack and the nest is subjected to mechanical vibration.

 After suitable time the particles that passes through one sieve and retained on the next finer sieve are collected and weighed.

 Frequently the powder is assigned the size of the screen through which it passes, on which it is retained or the mean of the two values.

Question 16

what are the limitations for the sieving method

Answer 16

 Sieving errors would result from a number of variables including sieve
loading, intensity and time of agitation. Care must be taken to ensure that the correct techniques are employed.

 For materials >150 μm, a sieve analysis and particle size distribution is accurate and consistent. However, for material that is finer than <150
μm, dry sieving can be significantly less accurate.

 Sieve analysis assumes that all particles will be round (spherical). Less spherical particles (e.g. elongated or flat) will give less reliable results.

 Unsuitable for material that adheres to the sieve or forms clumps.

Question 17

what are the different standards for powders based on sieving

Answer 17

 Very coarse (No. 8): All particles pass through a No. 8 sieve and not more than 20% pass through
a No. 60 sieve.

 Coarse (No. 20): All particles pass through a No.20 sieve and not more than 40% pass through a No. 60 sieve.

 Moderately coarse (No. 40): All particles pass through a No. 40 sieve and not more than 40% pass through a No. 80 sieve.

 Fine (No. 60): All particles pass through a No. 60 sieve and not more than 40% pass through a No.
100 sieve

 Very fine (No. 80): All particles pass through a No.80 sieve. There is no limit to greater fineness.

Question 18

what is microscopy

Answer 18

we can determine dm,p,f,a.

we use a light microscope (1-1000 micro)

scanning electron (0.05-1 micro)

transmission electron (0.001-0.05 micro)

Question 19

what are Dp,a,f,m

Answer 19

dp: perimeter diameter is based on a circle having the same perimeter as the particle.

da: projected area diameter is based on a circle of equivalent area to that of the projected image of a particle;

dF: Feret’s diameter is the distance between two parallel
tangents to the projected particle perimeter.

dM: Martin’s diameter is the is the length of a line that divides a
randomly oriented particle into two equal areas

dF and DM are affected by orientations

Question 20

what is the light microscopy procedure?

Answer 20

A suspension, diluted or undiluted, is mounted on a slide and placed on a mechanical stage.

The microscope eyepiece is fitted with amicrometer by which the size of theparticles can be estimated.

The field can be projected onto a screen where the particles are measured more easily.

Question 21

what are the disadvantages for microscopy

Answer 21

1. The number of particles that must becounted (300-500) to obtain a good estimation of the distribution makes the method is slow and tedious.
2. The diameter is obtained from only two dimensions of the particle: length and breadth. No estimation of the depth (thickness) of the particle is ordinarily available. (E.g. for a flaky particle the size measurement might be overestimated).

Question 22

what are the advantages for the microscopy method

Answer 22

Microscopic examination of a sample should be undertaken
even when other methods of particle size analysis are available, because the presence of agglomerates and particles of one or more than one component can be detected properly by microscopy but overlooked by other methods.

Question 23

whats stokes equations ? for strokes diameter

Answer 23

v= h\t= d^2 (ps-p0)g \ 18 n

dst= (Stokes diameter)
h = height or sedimentation distance
η = viscosity of the medium
v = rate of settling
t = time
ρs = density of the particles
ρo= density of dispersion medium,
g = acceleration due to gravity

Question 24

The Stoke’s equation holds exactly only for spheres falling freely
without hindrance and at a constant rate.
The law is applicable to irregularly shaped particles of various
sizes as long as one realizes that the diameter obtained is a
relative particle size equivalent to that of sphere falling at the
same velocity as that of the particles under consideration. (i.e.
equivalent Stokes diameter).
The particles must not be aggregated or clumped together in
the suspension since such clumps would fall more rapidly than
the individual particles, and erroneous results would be
obtained (deflocculating agent may be needed).

Question 25

what are the ranges for sedimentation method

Answer 25

Range of analysis:
Gravitational sedimentation: 5-1000 microns
Centrifugal sedimentation: 0.5-50 microns

Question 26

how do we do the pipette (andreasen) method

Answer 26

 The Andreasen apparatus usually consists of a 550-mL vessel.

 In contains a 10-mL pipette sealed into a ground-glass stopper.

 When the pipette is in place in the cylinder, its lower tip is 20 cm below the surface of the suspension.

 Particle size distribution can be determined by examining the
powder as it sediments.

 The powder is dispersed uniformly or introduced as a thin layer in
a fluid.

 The powder should not be soluble in the fluid, but should be easily dispersed (wetting agent might be added to the fluid).

Question 27

how do we use the balance method

Answer 27

The increase in weight of sedimented particles falling onto a
balanced pan suspended in fluid is recorded with respect to
time.

Question 28

what is centrifugal sedimentation

Answer 28

 One of the limitations of gravitational sedimentation it is that it is not suitable for particles < 5 microns:

 in this case the test becomes too slow and less accurate.  This can be minimized by increasing the driving force of sedimentation by replacing the gravitational force with a larger
centrifugal force

Question 29

what is the electric sensing zone method (coulter counter)

Answer 29

used for Dv (voulme)

range: 0.1-1000 micro

very accurate but esxpensive

the disperesed should be highly diluted to avoid conicidence ( when one or more partical over lap )

 Powder samples are dispersed in an electrolyte solution to form
a very diluted suspension.

 The particle suspension is drawn through an orifice where electrodes are situated on either side and surrounded by
electrolyte solution.

 As the particle travels through the orifice, it displaces its own
volume of electrolyte solution.

 The change in electrical resistance between the electrodes is proportional to the volume of the particle (volume of the electrolyte solution displaced).

Question 30

what is laser light scattering

Answer 30

low angle:
for Da and Dv
uses light scattering off particales suspended in air
from 0.5-1000 micro

 For particles (i.e. >1 µm) that are much larger than the wavelength of light, any interaction with particles causes light to be scattered in a forward direction with only a small change in angle (Fraunhofer diffraction). The angle of scatter is inversely proportional to the particle diameter.

 Laser light is passed through a dilute suspension of the particles. The light is scattered by the particles, and is detected by detector which measures light intensity over a range of angles.

angle diffraction = 1\particle size

Question 31

what is PCS

Answer 31

 Based on the Brownian movement (random motion of small particles
caused by collisions with the smaller molecules of the suspended fluids).

 It analyses the constantly changing patterns of laser light, scattered by
particles in Brownian movement.

The rate of change of scattered light can be related to the particle size.

5. Laser light scattering
   Equivalent Diameter for PCS: Hydrodynamic diameter (dn) Particle size range: 1nm- 5μm