powders
DESCRIPTION
POWDERS. Powders as a Dosage Form. Powders are prepared either as dusting powders which are applied locally, dentifrices, products for reconstitution, insufflations and aerosols. . Advantages of Powders as a dosage form: Flexibility in compounding and good chemical stability. - PowerPoint PPT PresentationTRANSCRIPT
POWDERS
Powders as a Dosage Form
Powders are prepared either as dusting
powders which are applied locally, dentifrices,
products for reconstitution, insufflations and
aerosols.
Advantages of Powders as a dosage
form:
Flexibility in compounding and good chemical
stability.
Disadvantages of powders as a dosage
form:
• Time-consuming to prepare
• Not suited well for dispensing the unpleasant-
tasting or
hygroscopic drugs.
• Inaccuracy of dose for bulk powders.
The dose is influenced by many factors, including
size of measuring spoon, density of powder,
humidity, degree of settling and fluffiness due to
agitation.
Preparation of powder dosage forms
Size reduction
Reduction of particle size of all ingredients with
the same range to prevent separation of large and
small particles.
When granular or crystalline materials are to be
incorporated into a powdered product, these
materials are triturated individually and then
blended together in the mortar.
TriturationThis term refers to the
process of reducing
substances to fine particles
by rubbing them in a mortar
with a pestle. This results in
blending powders and
breaking up soft aggregates
of powders.
Pulverization by InterventionThis is the process of reducing the state of solids with the additional material as volatile solvents which can be removed easily after the pulverization has been completed and the powdered material is obtained.This technique is applied to substances which are gummy and tend to reagglomerate or which resist grinding.
Example:Camphor which cannot be pulverized easily by trituration because of its gummy properties, can be reduced to a fine powder by the addition of a small amount of alcohol or other volatile solvent. Iodine crystals can be triturated with the aid of a
small quantity of ether.
Levigation
In this process a paste is first formed by the
addition of a suitable non-solvent to the solid
material.
Particle-size reduction then is accomplished by
robbing the paste in a mortar with a pestle.
Levigation technique is used to incorporate solids
into ointments and suspensions.
Blending (Mixing)
Blending is used when two or more substances are
to be combined to form a uniform powder mixture.
Depending upon the nature of the ingredients and
the amount of powder to be prepared mixing may be
by spatulation, trituration, sifting, tumbling or by
mechanical mixers.
This method is used when small amounts of powders
are to be blended by the movement of a spatula
through the powders on a sheet of paper or an
ointment slab.
Spatulation
Trituration
The method may be employed
both to reduce and mix
powders.
Porcelain or Wedgewood
mortar is
used.
For chemicals that may stain
the
porcelain or Wedgewood
surface,
a glass mortar may be
preferred.
When potent substances are to be mixed with a
large amount of diluent, geometric dilution method
is employed to ensure the uniform distribution of the
potent drug. By this method, the potent drug placed
upon an equal volume the diluent in a mortar and
the mixture is mixed by trituration. Then a second
portion of diluent equal in volume to the powder
mixture in the mortar is added, and the trituration is
repeated. This process is continued by adding equal
volumes of diluent to that powder present in the
mortar and repeating the mixing until all of the
diluent is incorporated.
Powders may also be mixed by passing them
through sifters.
This process results in a light fluffy product.
This process is not acceptable for the incorporation
of potent drugs into a diluent base
Sifting
Tumbling
The powder enclosed in a large container which
rotates generally by a motorized process.
Such blenders are widely employed in industry to
blend large amounts of powder.
Problems in powder manufacture
The incorporation of volatile
substances, eutectic mixtures,
liquids and hygroscopic substances
into powders presents problems
that require special treatments.
The loss of camphor, menthol and essential oils
by volatilization when incorporated into powders
may be prevented or retarded by use of heat-
sealed plastic bags or by double wrapping with a
waxed or glassine paper inside a bond paper.
Volatile Substances
Liquids result from the
combination of phenol, camphor,
menthol, thymol, antipyrne,
phenacetin, acetanilid, aspirin,
salol at ordinary temperatures.
Eutectic Mixtures
These eutectic mixtures can be incorporated
into
powders by addition of an inert diluent or
absorbent.
kaolin, starch, bentonite are used as absorbents
Incorporation of 20% silicic acid (particle size,
50 µm)
prevented eutexia with aspirin, phenyl salicylate.
This technique offers the advantage of extended
product stability.
Magnesium carbonate or light magnesium oxide
are used commonly as effective diluents for this
purpose. An amount of diluent equal to the eutectic
compounds is sufficient to prevent liquefaction for
about 2 weeks.
Each eutectic compound should be mixed first with
a portion of the diluent and gently blended together,
preferably with a spatula on a sheet of paper.
Liquids may be incorporated into divided powders.
Magnesium carbonate, starch or lactose may be
added
to increase the absorbability of the powders if
necessary.
When the liquid is a solvent for a nonvolatile heat-
stable
compound, it may be evaporated gently on a water
bath.
Lactose may be added during the evaporation to
increase
the rate of solvent loss by increasing the surface
area. Some extracts and tinctures may be treated in
this manner, although the use of an equivalent
amount of a powdered extract is a more desirable
technique.
Liquids
Substances that become moist because of affinity
for
moisture in the air may be prepared as divided
powders
by adding inert diluents.
Double-wrapping is desirable for further
protection.
Extremely Hygroscopic compounds cannot be
prepared
as powders.
Hygroscopic Substances
Use and Packaging of Powders
Depending upon their use, powders are
packaged and dispensed in two main ways, as
buck powders or as divided powders.
Example of the bulk powders are:
Oral powders: as antacid and laxative powders,
it can be taken by mixing an amount of powder
in a portion of water or other beverage and
swallowing as solution or suspension;
Douche powders: generally dissolved in warm
water and used as antiseptics or cleansing
agents for a body cavity as for vaginal use;
Douche powders are Dispensed in wide-mouth
glass jars serves to protect against air and
moisture or loss of volatile materials
BULK POWDERS
• Dusting Powders are usually dispensed in sifter
containers for convenient application to the
skin;
• Foot powders and talc powders are currently
available
as aerosols.
Dentifrices: Dental cleansing powders, used in
dental hygiene;
Denture powders, some used as dentifrices and
others as adhesives to hold the dentures in
place;
Dusting Powders: Medicated or non-
medicated for external application for
various parts of the body as
lubricants, protectives, absorbents,
antiseptics,
astringents and antiperspirants
agents.
All powders should be stored in tightly closed
containers
for Protection against humidity, air oxidation and
loss of
volatile ingredients.
Dispensing powdered drugs in bulk amounts
limited to
non-potent substances.
Powders containing potent substances or those
that
should be administered in controlled dosage are
Supplied to the patient in divided amounts.
After the powder has been mixed, it may
be divided into individual doses.
Each divided portion of powder may be placed on
a
small piece of paper or metal foil which is then
folded or
in small heat-sealed plastic bags so as to enclose
the
medication.
Hygroscopic and volatile drugs can
be protected by using a waxed paper;
divided POWDERS
Pharmaceutical powders may be classified as free-
flowing or cohesive (non-free-flowing).
Flow properties are significantly affected by
changes in
particle size, density, shape, electrostatic charge,
and
adsorbed moisture, which may arise from
processing or
formulation.
Preformulation, powder flow should be
determined for
the improvement of pharmaceutical formulation
and
consequences of processing.
This subject becomes vital for the development of
a
commercial solid dosage form containing a large
percentage of cohesive material.
1- Particle size: Frictional and
cohesive forces (resistance to
flow) are increased as the particle
size is reduced .
Very fine particles do not flow as large particles.
In general, particles in the size range of 250-2000
µ flow freely if the shape is agreeable. Particles in
the size range of 75-250 µ may flow freely or cause
problems, depending on shape and other factors.
With particles less than 100 µ in size, flow is a
problem.
Factors affecting Powder
Flowability:
2- Density and porosity: -
Particles with density and low
porosity tend to posses free
flowing properties.
3- Particle shape: Rough
irregular particles presents more
points of contact than smooth
spherical particles thus Spherical
particles flow better than needles4- Particle size distribution: Larger amount of
fines can inhibit poor flowing.
5- Moisture content: Drying the powders will
reduce the cohesiveness.
Flow rate determination • Powder flows through an orifice onto
an electronic balance.
• Flow rate is determined by measuring weight of
powder
pass through an orifice per time (g/sec).
• Several flow rate determinations through a variety
of
orifice sizes (1/8 to 1/2 inches) should be made.
• In general, the greater the standard deviation
between
multiple flow rate measurements, the greater is
the
weight variation in products produced from that
powder.
Particle Size Analysis
The particles of pharmaceutical powders may be
coarse to extremely fine.
Standard Sieve Shaker
The USP utilizes terms which are
related to the proportion of
powder that is capable of
passing through the openings of
standardized sieves of varying
dimensions in a specified time.
Opening of Standard Sieves
Sieve Opening
Sieve Number(No of pores
/inch2) 9.5 mm 2 5.6 mm 3.54.75 mm 42.36 mm 82.00 mm 10850 µm 20600 µm 30425 µm 40300 µm 50250 µm 60212 µm 70180 µm 80150 µm 100125 µm 120 75 µm 200 63 µm 230 53 µm 270 45 µm 325 38 µm 400
Sieve Analysis
Coarse powder -All particles pass through
No. 20 sieve and not more 60% through No. 40
sieve.
Moderately Coarse powder -All particles pass
through No. 40 sieve an not more than 60%
through No. 60 sieve
Fine powder -All particles pass through No. 80
sieve. There is no limit as to greater fineness.
Very Fine powder -All particles pass through No.
120 sieve. There is no limit as to greater fineness.
Methods of particle size determinations include
techniques That provide average particle size by
weight (sieve method, light scattering,
sedimentation method), and average particle size by
volume (light scattering, electronic sensing zone,
light obstruction, air permeation and the optical
microscope).
Methods for the determination of particle size:
Sieving: In which particles are
passed by mechanical shaking
through a series of sieves of
known and successively smaller
size and the determination of
the proportion of powder
passing through or being held
on each sieve (range: from
about 50 to 3360 micrometers,
depending upon sieve sizes).Sieve Analysis
Microscopy: In which the particles are sized
through the use of a calibrated network
background (range: 0.2 to 100 micrometers)
Sedimentation :
Particle size is determined by measuring the
settling velocity of particles through a liquid
medium in a gravitational or centritugal
environment.
Sedimentation rate may be calculated from Stokes'
law
Using the "Andreasen Pipet.“
The Andreasen pipet is designed where a sample
can be removed from the lower portion at selected
time intervals. The powder is dispersed in a
nonsolvent in the Andreasen Pipet.
Agitated, and 20 mL samples removed over a period
of time.
Each 20 mL sample is dried and weighed.
Light energy diffraction:
Particle size is determined by the reduction in light
reaching the sensor when the particles, dispersed in a
liquid or gas, passes through the sensing zone.
Laser holography:
in which a pulsed laser is fired
through an aerosolized particle
spray and photographed in three
dimensions with a holographic
camera,
Angles of Repose Ф The angle of repose is a relatively simple
technique for estimating the flowability of a
powder.
Such measurements give at least a qualitative
assessment of the internal cohesive and
frictional effects under low levels of external
loading, as might apply in powder mixing, or in
tablet die or capsule shell filling operations.
The height and diameter of the resulting cone is
measured.
It is the maximum angle that can be obtained between
the free standing surface of a powder heap and the
horizontal plane.
The angle of repose can be
determined experimentally by
allowing a powder to flow through
a funnel and fall freely onto a
surface.
D
h2Tan Ф =
Angle of repose Ф can be defined by the equation:
Where:
h is the height of the powder cone
D is the diameter of the powder cone. Values of Ф between 20° - 40° indicate
reasonable flow.
Powders with low angles of repose will flow
freely
Above 50° the powder flows only with great
difficulty.
Mass-Volume Relationships The mass of a bulk powder can be accuracy determined
but measurement of the volume is more complicated.
The main problem arises in measuring the volume of
bulk powders is the presence of three types of air spaces or voids between particles.
1.Open intraparticulate voids:-
Those within a single particle but open to the
external
environment.
2. Closed intraparticulate voids:-
Those within a single particle but closed to the
external
environment.
3. Interparticulate voids:-
The air spaces between individual particles.
Therefore, at least three interpretations of
"powder volume may be proposed
The true volume (Vt):
The total volume of the solid particles, which
excludes all
spaces greater than molecular dimensions, and
which has
a characteristic value for each material.
The granular volume (particle volume) (Vg):
The cumulative volume occupied by the particles,
including all intraparticulate (but not
interparticulate)
voids.
The bulk volume (Vbulk):
The total volume occupied by the entire powder
mass
under the particular packing achieved during the
meas
POROSITY, VOID AND BULK
VOLUMEPacking and flow of powders are important for:
Impacting the size of container required for
packaging
The flow of granulations
The efficiency of the filling apparatus during the
tabletting
Encapsulating process.
A number of characteristics can be used to
describe powders including:
Porosity, true volume, bulk volume, apparent
density, true density, and bulkiness.
The void is the space between the particles which
resulting in a porosity.
If particles are not uniform, the smaller particles will
slip into the void spaces between the larger
particles and decrease the void areas.
The Void =
bulk
tbulk
V
VV Where:
Bulk Volume, V bulk = The volume occupied by a
selected
weight of a powder.
The True volume, Vt = The space occupied by the
powder
exclusive of spaces greater
than
the intramolecular space.
bulk
tbulk
V
VV The Porosity = X 100
The bulk volume = True volume + Porosity
APPARENT DENSITY, TRUE DENSITY AND
BULKINESS
Bulk density is of great importance for capsule
filling, tablet Compressibility and for the
homogeneity of formulation in which there are
large differences in drug and excipient densities.
Apparent bulk density (g/ml) is determined by
pouring presieved (40-mesh) bulk drug into a
graduated cylinder via a large funnel and
measuring the volume and weight "as is."
The Apparent Density Pa= bulkV
theSampleofWeight
The True Density P =V
theSampleofWeight
The bulkiness, B = is the reciprocal
of the apparent densityB = 1 /pa
Powders with low apparent density and large bulk
volume are "light" powders, and those with high
apparent density and small bulk volume are "heavy"
powders.
Tapped density is determined by placing a
graduated cylinder containing a known mass of drug
or formulation on a mechanical tapper apparatus,
which is operated for a fixed number of taps (≈1000)
until the powder bed volume has reached a
minimum.
Using the weight of drug in
the cylinder and this
minimum volume, tapped
density can be determined.
Where:
Pt = The tapped bulk density
P0 = The initial bulk density
Compressibility
% Compressibility = X 100
t
ot
P
PP
A simple indication of the flow property of a powder
is given by using of compressibility index (I)
Where:
V = the volume occupied by a sample of the powder
after
tapping procedure
Vo = the volume before tapping.
Values of I below 15% usually give rise to good flow
characteristics, but above 25% indicate poor
flowability.
Compressibility index (I) = X 100
01V
V