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

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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