Effect of Micromeritics Property on Preformulation: Particle Size, Particle Shape & Density

1.      Particle Size:

·         Characterized using these term:

o   Very coarse (#8)

o   Coarse (#20)

o   Moderately coarse (#40)

o   Fine (#60)

o   Very fine (#80)

·         Size of the particles may be expressed as follows:

o   Surface diameter, ds

o   Volume diameter, dv

o   Projected diameter, dp

o   Stokes diameter, dst

o   Sieve diameter, dsieve

o   Volume – surface diameter, dvs – same volume to surface area ratio

Table 1.1: Common Techniques for Measuring Fine Particles of Various Sizes
Technique	Particle size (micro meters)
Microscopic	1-100
Sieve	>50
Sedimentation	>1
Elutriation	1-50
Centrifugal	<50
Light scattering	0.5 - 50

Methods to determine particle size:

·         Sieving:

o   Simple & inexpensive

o   Dry powder require

·         Microscopy:

o   Particle size determine by calibrated grid background

o   Calibration factore: 

o   (No. of division of stage micrometer/No. of division of eye-piece micrometer)*100

o   Slow and tedious method

·         Sedimentation method:

o   Andersen pipette is used

o   Particle size calculated by stokes law

o  

o   Where,

§  h = distance fall in time, t

§  no = viscosity of medium

§  ps = density of particles

§  po = density of dispersion medium

§  g = gravitational acceleration

§  t = time

·         Light scattering:

o   Particle size determine by the diversion of light pathway that reaching the sensor.

o   Quick and fast

Particle size effect on following:

·         Formulation:

o   Uniform particle size and shape have good flow properties

o   Uniform size particle produce good & uniform dispersion

o   Uniform size produce good compaction during tablet manufacturing

§  Defects in tablets have less chances

o   Size alsoplays a role in the homogeneity of the final tablet.

o   Large differences in size exist between the active components and excipients,  de-mixing effects can occur.

·         Bioavailability

o   Uniform and smaller size particles have good absorption and therefore good bioavailability.

o   For example, the bioavailability ofgriseofulvin and phenacetin is directly related tothe particle size distributions of these drug

o   It is now generally recognized that poorly soluble drugs showing a dissolution rate- limiting step in the absorption process will be more readily bioavailable when  administered in a finely subdivided state than as a coarse material

·         Stability:

o   Smaller particle (in colloidal range) improve stability of dispersion

o   Bcz,

§  Brownian motion observed

§  Therefore sedimentation is law

2.      Particle Shape:

·         Formulation:

o   Sphere particle have good flow property compare to other

o   Irregular shape particle have not good flow property because they cloge during movement

o   Packing and compaction property depend on particle shape

o   Parenteral formulation have only sphere particles

·         Bioavailability:

o   Surface area  à Dissolution à absorption

o   Surface area also depend on shape of particle

o   Increase surface area à increase bioavailability

·         Stability:

o   Sphere particle take more time to stable compare to other shape of particle

3.      Density:

The ratio of mass to volume is known as density

·         Types of density:

o   Bulk density:

§  Bulk drug powder is sieved through 40 mesh screen. Weight is taken and poured into a graduated cylinder via a large funnel. The volume is called bulk volume.

o   Tapped density:

§  Bulk powder is sieved through 40 mesh screen.

§  Weight is taken and poured into a graduated cylinder.

§  The cylinder is tapped 1000 times on a mechanical tapper apparatus.

§  The volume reached a minimum – called tapped volume.

o   True density: It actual density of the solid material.

§  Solvents of varying densities are selected in which the powder sample is insoluble.

§  Small quantity of surfactant may be mixed with the solvent mixture to enhance wetting and pore penetration.

§  After vigorous agitation, the samples left to stand undisturbed until floatation or settling has reached equilibrium.

§   The density of that solvent is determined accurately with a pycnometer.

o   Granule density:

§  may affect compressibility, tablet porosity, disintegration, dissolution

·         Source of variation of bulk density:

o   Method of crystallization, milling, formulation.

Significance:

·         Bulk density:

o   Bulk density is required during the selection of capsule size for a high dose drug.

o   In case of low dose drug mixing with excipients is a problem if the bulk densities of the drug and excipients have large difference.

·         Tapped density:

o   Knowing the dose and tapped density of the formulation, the capsule size can be determined.

·         True density:

o   From bulk density and true density of powder, the void volume or porosity can be measured.