Particle Size and Particle Size Distribution / Physical Pharmaceutics / What is volume of distribution in pharmacology / pharmacy notes download

 Physical Pharmaceutics

Micromeritics and Powder Rheology

Micromeritics is the science and technology which deals with small particles. There are two types of properties for a particle to characterize.

 Fundamental Properties 

Surface area, particle size and distribution, particle number, particle volume, particle shape.

 Derived Properties

 Porosity, density, bulkiness, flow ability (Flow property). 

Particle Size and Particle Size Distribution 

Particle size is quoted as the diameter of the sphere that has same weight (Weight based diameter) or same volume (Volume based diameter) or same surface (area based diameter) or same drag coefficient /sedimentation velocity (Hydrodynamic or Aerodynamic based diameter), to the given particle. 

Types of powders according to particle size

 Monodisperse powder All particles are of same size.

 Polydispersed powder Particles of different size. 

Generally, powder sample contains number of irregular shaped three dimensional particles so we generally consider average particle size. 

Average particle size Average size of the particles which are distributed in the system

    1. Microscopy Range of analysis

•   By transmission electron microscope 0.001–0.1 micron. yy By scanning electron microscope 0.01–1000 micron. yy 
• By light microscope 1–1000 micron.

 Advantages Easy and convenient 

• A size-frequency distribution curve can be plotted by counting the number of particles in a size range. yy
•  Can detect the presence of agglomerates and particles of more than one component. 

Disadvantages 

• Diameter is obtained from only two dimensions— length and breadth. 
•  No estimation of the depth (thickness) of particle is available.
• The number of particles that must be counted to get a good estimate of the distribution makes the method slow and tedious. 

2. Sieving 

 This method utilizes a series of standard sieves calibrated by the National Bureau of Standards. 

Range of analysis 

We obtain particle size range 5–12000 µm.

 Air jet sieving method

 Another type of sieve analysis called air jet sieving, uses individual sieves rather than a complete nest of sieves. A reverser air jet circulator beneath the sieve mesh, blowing oversize particles away from the mesh to blocking. It is better than mechanically vibrated sieve analysis, although with finer particles agglomeration can become a problem. 3. Sedimentation yy Particle size may be indirectly determined by measurement of rate of sedimentation in a Gravitational field (Figure 1.1)

•  A number of classical techniques based on sedimentation methods, utilizing devices such as the Anderson pipette or recording balances. 

Stokes gave a theoretical description of the motion of falling under the influence of gravity.

 dst = [18 η µ/(Pp – PL) g ]½ 

Stokes law of sedimentation 

•  Rate of settling = d2 ( 1 – 0 ) g/18 η 

            where d is diameter of particle; 

             1 is density of particle; 

             0 is density of liquid and η is viscosity of liquid. 

• Used only for dilute suspension (less than 2% dispersed particles)

4. Elutriation 

• Elutriation is a procedure in which the fluid moves in the direction opposite to sedimentation movement so that in the gravitational force, the particle will move vertically downwards and fluid moves vertically upwards (Figure 1.2). 

•  If velocity of fluid is higher than the particle are carried upwards and vice versa.

 

5. Electronic scanning zone (coulter counter)

 Particles are suspended in electrically conductive fluid. The suspension flows through suitable aperture with an immersed electrode on either side and particle concentration is arranged so that one particle travels at a time. When the particle passes, some resistance is seen and that change is measured as particle. 

Coulter-Current When a suspended particle travels across the orifice, it displaces its own volume of electrolyte. This causes change in electrical resistance. Its main advantages are: 

1. Fastest counting. 

2. 1000 particles counted in one second. 

3. More reliable since number of particles are counted. 

4. To study particle growth and dissolution and the effect of anti-bacterial agent on the growth of microorganism.

 6. Surface method 

Take some powder and add air and liquid to it. Powder absorbs liquid and air’s mono-molecular layer on its surface. This absorbed volume can give mean of powder’s particle size 

7. Fluid classification method

 A number of size analysis methods for powder in the sub sieve depend on the movement of the particle in a fluid. The behaviour of sphere in a fluid can be expressed by Stroke’s law. There are several cumulative methods: 

1. Pipette method 

2. Hydro meter method

 3. Pressure method 

4. Turbidimetric method 

8. Laser light scattering methods

•  In this method, the particle can be presented either in liquid or in air suspension.
•   Both the large particle and small particle analysers are based on the interaction of laser light with particles.
•   Royco/HIAC–based on light blockage principle. 

9. X-ray diffraction method Principle 

•  An x-ray irradiation produces a highly specific diffraction pattern from a crystal of material. 
•  An X-ray diffraction pattern from the crystal is formed and a series of dots of varying intensity with fixed angular and is recorded on photographic film. 
•  It is a powerful tool for particle size analysis.

 Advatages Very sensitive and used in identification of polymorphs.

 Disadvantages Very expensive 

10. Cascade impaction 

Size Range 0.1-80 microns Material Particles of all kind 

•  It can be used to obtain the size distribution of an aerosol. 
• Air samples are withdrawn through device which consists of several stages on which particles are deposited on impaction plate. 
• Particles will impact on certain stage depending on their size. Conclusion This method is suitable to determine the distribution of particles of respirable size. 

11. Rotating drum method 

Material Dry powder, Granulates, Friable products. 

Size Range 0.5–10000 microns 

•   This method is suitable to determine the distribution of particle of respirable or inhalable size. Properties of drug that are affected by particle size and particle size distribution 

• yy Surface area

•   Density, porosity and compressibility 

•  Angle of repose and flow property 

• Bulkiness and packaging criteria 

•  Hygroscopicity 

•  Electrostatic charge Surface area 

•  As the particle size decreases, the surface area of the particle increases. 

•  Surface area is important for drug absorption, dissolution, solubility and bioavailability. 

•  The particle size and surface area of drug exposed to the medium can affect actual solubility. 

 Log (S/S0 ) = [2γ V/2.303 + RTr ]

 S = Solubility of small particle S

0 = Solubility of large particle 

Y = Surface tension 

V = Molar volume 

R = Gas volume 

T = Absolute temperature 

r = Radius of small particle

 The equation is used to estimate the decrease in particle size required to increase in solubility. 

Noyes Whitney equation 

dC/dt = KS(CS -CF )

        dc/dt = rate of dissolution

             K = dissolution rate constant 

              S = surface area 

            Cs = concentration of drug in immediate proximity of dissolving particle, that is,                          solubility of drug 

            Cf = concentration of drug in bulk fluid 

•   According to Noyes Whitney equation, increase in the total surface area of drug in contact with GIF will cause increase in dissolution rate because of particles initially wetted by GIF. The effective surface area exhibited by drug is directly proportional to the particle size. 

•  Hence smaller the particle size, greater will be effective surface area and higher dissolution rate and it will result in higher bioavailability