NORTH SOUTH UNIVERSITY

NAME: MAHMUDA AKTER MARZIA

ID- 2014151649
COURSE NAME: PHR210; SEC: 02
SUBMITTED BY: MAHMUDA AKTER MARZIA
SUBMITTED TO: ZAHIDUL ISLAM ZAHID

MICROMERITICS

The term micromeritics was given to the science and technology of small particles by
Dalla Valle. Micromeritics is thus the study of the fundamental and derived properties of
individual as well as a collection of particles[ CITATION AGA062 \l 1033 ].
INTRODUCTION:
Accurate determination of particle size has become essential in many industries, as it is a
fundamental physical characteristic that must be selected, monitored, and controlled from the
raw material source to the finished product. There is an optimum particle size, or at least a
smallest and largest acceptable size, for most formulations involving particles. The key to
accurate particle size determination is selecting the most appropriate sizing instrument for a
particular application. If all particles were spheres, their size would be defined explicitly by their
diameter or radius; if cubical, the length along one edge would be characteristic; and, if of
another regular shape, another equally appropriate dimension could be chosen. Unfortunately,
the great majority of particles are quite irregular and an arbitrary definition of size is the only
simple solution. Moreover, typical collections of particles include many different sizes and
shapes. Therefore, a definition is required that accommodates this diversity, and the “equivalent
spherical diameter (or radius)” satisfies this requirement. Equivalence of size means that a
specific, experimentally measured attribute of the particle is the same as that of a sphere of a
certain size. In other words, when the particle under test and a sphere of a specific size are
exposed to the same conditions, the identical reaction occurs. Examples of reactions that may
occur are the light scattering characteristics (scattering equivalency), the attainment of a certain
terminal settling velocity (settling equivalency), or the displacement of fluid (volume
equivalency). Therefore, obtaining particle size information about a material may be
accomplished by a number of techniques, each of which test for a specific equivalency.
Micromeritics offers instruments that use three different techniques. This allows one to select the
best technique for a material and application rather than trying to adopt one method to all
situations. The sizing techniques used by micromeritics are light scattering, sedimentation, and
electric sensing zone. As is always the design objective with micromeritics instruments, each
instrument provides the user with high data quality (resolution and accuracy) and with a
dependable measuring tool (reliability, repeatability, reproducibility)[ CITATION Mah18 \l 1033 ].
IMPORTANCE IN PHARMACY:
The study of particle size and particle size distribution has a number of applications in the field
of pharmacy including the following:
1.The physical properties of powders such as bulk density, porosity and compressibility are
dependent on the particle size distribution. For example, the bulk density of light and heavy
magnesium carbonate differs because of the difference in their particle size.
2. The flow properties of powders are dependent upon the particle size, size distribution as well
as the particle shape. Asymmetric particles have poor flow characteristics and hence granulation
techniques are used to convert blends of drug and other additives into particles of uniform size
having good flow properties.
3. The rate of dissolution of poorly soluble drugs is directly related to the size of the drug
particles. In general, a decrease in the particle size of the drug increase the dissolution rate.
4. The chemical properties of particles such as surface oxidation also depend on the particle size.
Smaller the particle size, more is the surface area exposed for oxidation.
5. Properties of drugs such as rate of absorption and hence the pharmacological activity depend
on the particle size.
6. Elegance of pharmaceuticals preparations such as emulsions, suspensions, ointments often
depend upon the particle size of the dispersed phase.
7. The release characteristics of drugs from ointments, creams and suppositories are dependent
on the particle size of the dispersed drug.
8. Particle size of the dispersed drug also influences the spreadability and performance of some
cosmetic preparations like dusting powders.
9. Particle size and size distribution has a profound influence on the uniform mixing of solids.
10. The stability of systems such as colloids, suspensions and emulations depend on the particle
size. As the particle size increases, the stability of these systems decreases.
11. Even the feel, texture and color of certain drugs depends upon the particle size. For example,
the difference in color of yellow and red mercuric oxide is due to the differences in their particle
size.
12. Processes such as extraction and drying are accelerated following a reduction in the particle
size of the material.
13. The absorption capacity of a material also increases by a decreases in its particle size
[ CITATION AGA062 \l 1033 ].
FUNDAMENTAL PROPERTIES OF COLLECTION OF PARTICLES:
The following are the fundamental properties of powders from which other properties can be
derived.
1. Particles size and size distribution.
2. Methods for determining particle size.
3. Density and flow properties of powders.
DEFINITION:
It is the science and technology of small particles.
The unit of particle size used in the micrometer, micron, and equal to 10^-6 m.
As a particle size decreases, area increases.

Micromeritics is the science and technology of small particles. Knowledge and control of the
size and the size range of particles are of significant importance in pharmacy because the size
and surface area of a particle related to the physical, chemical, and pharmacologic properties of a
drug. The particle size of a drug can affect its release from dosage forms that are administered
orally, parenterally, rectally and topically. In the area of tablet and capsule manufacture, control
of the particle size is essential in achieving the necessary flow properties and proper mixing of
granules and powder.
PARTICLE SIZE AND SIZE DISTRIBUTION:
In a collection of particles of more than one size, two properties are important, namely.
1. The shape and surface are of the individual particles.
2. The particle size and size distributions (The size range and number or weight of particles)
[ CITATION Nan15 \l 1033 ] .
PARTICLE SIZE:
Particles can be defined by size, shape (length, breadth, and height), volume (liter), and surface
area (cm^2) properties and can be either made of solid substance or liquid. All these parameters
are important in bulk properties, product performance, process ability, stability, and appearance
of the end product when it comes to pharmaceutical formulation and manufacturing. In context,
particle size is the term which is mostly used for denoting the dimensions of solid powders,
liquid particles, and gases bubbles. In the pharmaceutical world, particle size is linked to
development of new chemical entities (NCEs) which improve dissolution rate, i.e., the
absorption rate of poorly soluble drug can be improved by reducing the particle size which
ultimately improves the bioavailability of drugs. Physical properties of active pharmaceutical
ingredients and excipients largely depends on their particle size which are used to formulate
pharmaceutical dosage form. That is because particle size and shape have profound impacts on
each and every manufacturing step, including mixing, granulation, drying, milling, blending,
coating, encapsulation, and compression. As per ICH Guidelines, particle size is critical to solid
dosage form and liquids containing undissolved particles (for example Suspension and
emulsion), influencing the safety, efficacy, and stability of the formulation. From the tablet and
capsule manufacturing perspective, controlling the particle size is foremost to reach the product
with acceptable standards for the FDA, because particle size influences a large number of
parameters in processing, including capsule filling, porosity, and flow ability. Likewise, in
suspension, the physical properties of the fluid and the size of particles both have an effect on
precipitation and aggregation which affect the stability of formulation. The particle shape is
playing a major role in particle size distribution. The shape of a particle is not always regular
(symmetrical) and can be in asymmetrical or uneven.

Fig: 01- The scale of particle size in drug delivery. Importance of particle size in lymphatic drug
delivery, oral, intranasal, ocular, transdermal, brain/tumor, aerosol, intraperitoneal delivery.
Different delivery routes may require different particle size.
Therefore, it is difficult to measure through a meaningful diameter. Complex statistical analysis
of irregular shaped particles has been derived from different geometries. However, particle size
is expressed as equivalent spherical diameter to correlate with the size of particles to that of a
sphere with the same diameter, surface area, and volume. The measurement of size of irregular
particles depends upon which type of method is applied.
Particle size is a simple concept but it is a most critical process parameter in preformulation and
manufacturing. It is also true that the reduction of particle size impacts directly on the
bioavailability of drug. Thus regulatory agencies are now more concerned about particle size
specifications of active pharmaceutical ingredients and excipients. The major critical parameters,
such as dissolution and manufacturing process issues, are largely influenced by particle size
[ CITATION Mah18 \l 1033 ].
PARTICLE SIZE DSTRIBUTION:
When the number or weight particles lying within a certain size range is plotted against the size
range or mean particle size, a so-called frequency distribution curve is obtained. This is
important because it is possible to have two samples with the same average diameter but
different distributions.
MICROMERETICS APPLICATIONS:
1. Release and dissolution.
2. Absorption and drug action.
3. Physical stability.
4. Dose uniformity.
RELEASE AND DISSOLUTION:
Particle size and surface area influence the release of a drug from a dosage form. Higher surface
area allows intimate contact of the drug with the dissolution fluids in vivo and increases the drug
solubility and dissolution.
ABSORPTION AND DRUG ACTION:
Particle size and surface area influence the drug absorption and subsequently the therapeutic
action. Higher the dissolution, faster the absorption and hence quicker and greater the drug
action.
PHYSICAL STABILITY:
The particle size in a formulation influences the physical stability of the suspensions and
emulsions. Smaller the size of the particle, better the physical stability of the dosage form.
DOSE UNIFORMITY:
Good flow properties of granules and powders are important in the manufacturing of tablets and
capsules.
METHODS FOR DETERMINIG PARTICLE SIZE:
Many methods available for determining particle size such as optical microscopy, sieving,
sedimentation and particle volume measurement.
1. Optical microscopy (range: 0.2-100 micrometer).
2. Sieving (range: 40-9500 micrometer).
3. Sedimentation (range: 0.08-300 micrometer).
4. Particle volume measurement (range: 0.5-300 micrometer).
RANGE OF PARTICLE SIZES:
A guide to range of particle sizes applicable to each method is

OPTICAL MICROSCOPY (RANGE: 0.2- 100 MICROMETER):

Optical microscopy is a technique employed to closely view a sample through the magnification
of a lens with visible light. This is the traditional form of microscopy, which was first invented
before the 18th century and is still in use today. An optical microscope, also sometimes known as
a light microscope, uses one or a series of lenses to magnify images of small samples with visible
light. The lenses are placed between the sample and the viewer’s eye to magnify the image so
that it can be examined in greater detail [ CITATION smi18 \l 1033 ].
The microscope eyepiece is fitted with a micrometer by which the size of the particles may be
estimated. According to the optical microscope method, an emulsion or suspension is mounted
on ruled slide on a mechanical stage. The ordinary microscope used for measurement the particle
size in the range of 0.2 to about 100 micrometer.
Fig: Optical microscope (range: 0.2-100 micrometer).
DISADVANTAGE OF MICROSCOPIC METHOD:
1. The diameter is obtained from only two dimensions of the particle.
2. The number of particles that must be counted (300-500) to obtain a good estimation of the
distribution makes the method somewhat slow and tedious.
SIEVING (RANGE: 40-9500 MICROMETER):
Standard size sieves are available to cover a wide range of size. These sieves are designed to sit
in a stack so that material falls through smaller and smaller meshes until it reaches a mesh which
is too fine for it to pass through. The stack of sieves is mechanically shaken to promote the
passage of the solids. The fraction of the material between pairs of sieve sizes is determined by
weighing the residue on each sieve. The result achieved will depend on the duration of the
agitation and the manner of the agitation.
Fig: Sieving (range: 40-9500 micrometer)
SEDIMENTATION (RANGE: 0.08-300):
By measuring the terminal settling velocity of particles through a liquid medium in a
gravitational centrifugal environment using Andresen apparatus.
Fig: Sedimentation.
PARTICLE VOLUME MEASURMENT (RANGE: 0.5-500 MICROMETER):
In this type of machine the powder is suspended in an electrolyte solution. This suspension is
then made to flow through a short insulated capillary section between two electrodes and the
resistance of the system is measured. When a particle passes through the capillary there is a
momentary peak in the resistance, the amplitude of the peak is proportional to the particle size.
Counting is done by a computer.
DENSITY OF POWDERS:
Density is defined as weight per unit volume (w/v). During tapping, particles gradually pack
more efficiently, the powder volume decreases and the tapped density increases.

TYPES OF DENSITY:
1. True beauty: The true density or absolute density of a sample excludes the volume of the pores
and voids within the powder sample.
2. Bulk density: The bulk density value includes the volume of all of the pores within the powder
sample.
FLOW PROPERTIES OF POWDERS:
Powders may be free-flowing or cohesive (sticky).
Many common manufacturing problems are attributes to powder flow.
1. Powder transfer though large equipment such as hopper.
2. Uneven powder flow - excess entrapped air within powders – capping or lamination.
3. Uneven powder flow – increase particles friction with die wall causing lubrication problems
and increase dust contamination risks during powder transfer.
4. Powder storage, which for example result in caking tendencies within a vial or bag after
shipping or storage time.
5. Separation of small quantity of the powder from the bulk-specially just before the creation of
individual doses such as during tableting, encapsulation and vial foiling which affect the weight
uniformly of the dose (under or over dosage) [ CITATION Nan15 \l 1033 ].
IMPROVEMENT OF FLOW PROPERTIES:
1. Altering the particle size:
Increasing the average particle size of particles improves the flow properties due to reduction in
the cohesive forces. During tableting, fine powders are converted to coarse granules in order to
impart good flow properties to them.
2. Removal or addition of fines:
Presence of a small proportion of fines in a powder or granular mass may improve the flow
properties by filling up the pits and crevices on the surface of particles. On the other hand, larger
proportion of fines may retard the flow properties. Hence, an optimum concentration of fines is
desirable for best results.
3. Altering the particle shape and texture:
Spherical particles tend to have better flowability as compared to irregular particles. Hence,
techniques like spray drying may be used to give spherical particles with good flow properties.
Alteration of crystallization conditions may also produce particles of the desired shape and
texture.
4. Removing extra moisture:
Drying of powders in order to remove the moisture from surfaces can improve the flow
properties by decreasing the cohesiveness.
5. Altering the surface forces:
Reduction of electrostatic charges on particle surface by reducing frictional contacts such as
during transfer or during processes such as sieving can improve the flow properties.
6. Adding flow activators or Glidants:
Flow properties pharmaceutical powders may be improved significantly by the addition of
materials known as glidants. These act by forming a thin uniform film on the surface of particles
to reduce the adhesion and cohesion between particles. Examples of such materials include
magnesium stearate, starch and tale. The optimum concentration of glidants has been
experimentally demonstrated to be generally 1% or less and above this concentration usually
there is a decrease in flow rate. Colloidal silicon dioxide is another flow activator with a very
high specific surface area which acts by reducing the bulk density of tightly packed
powders[ CITATION AGA062 \l 1033 ].

References
AGARWAL, D. S. (2006). Micromeritics (2th ed.). New delhi, India: Vinod K. Jain.
Maheshwari, R. (2018). Micromeritics in pharmceutical product development. In P. Todke, Dosage form
design considerations (p. 600). ahmedahad, India.

Nanjwade, D. B. (2015). Micromeritics. slide, Omar Al- Mukhtar University, Pharmaceutics , Tobruk.

smith, Y. (2018, August 23). optical microscopy.