Technology of Solid Dosage Forms &Disperse

Systems

by/

Dr. Mekaiel Amiel Mekaiel M.Sc. Pharmaceutical Technology

Powders & Granules

Learning outcomes

By the end of this session student should be able to:

1. Define pharmaceutical powders.

2. Explain the detailed formulation and manufacturing unit operation involved in the manufacture of pharmaceutical powders.

3. Identify the excipients used and their role/function in the formula.

4. Describe different powder dosage forms and its uses.

5. Describe different techniques employed in production of powders.

6. Differentiate and compare between different types of powders.

TOPIC CONTENTS:

Powder: a) Introduction

b) Classification

c) Mixing of powders

d) Method of preparation

e) Advantages and disadvantages

f) Shelf life and storage

g) Containers

h) Packaging

i) Labeling

j) Pharmaceutical uses

Introduction

Powders are dry mixtures of finely

divided medicinal and nonmedicinal

agents intended for internal or external

use. Powders may be dispensed in bulk

form, or they may be divided into single-

dosage units and packaged in folded

papers or unit-of-use envelopes.

Definition:

Classification of Powders:

(a)Classification on the basis of use:

1)Bulk powder for internal use

2)Bulk powder for external use

3)Divided or unit doses powder

1).Bulk powder for internal use

• They are mixture of finely divided drugs

and\ or chemicals in a dry form that may be

intended for internal use (oral powders)

Types:

a) Oral powder

b) Powder spray

c) Dry powder inhalers

d) Effervescent powders

2).Bulk powder for external use

• They are mixtures of finely divided drugs

and/ or chemicals in a dry form that may be

intended for external use available in

multiple doses (dusting powder)

Types:

a) Dusting powders

b) Insufflations

c) Dentifrices

3) Divided powder

• Divided powder are similar formulation to

bulk powder but individual doses are

separately wrapped.

Types

a) Douche powders

b) Powder for injection

c) Effervescent powders

Size classification of powders

Particle size Analysis

The powders have been classified into:

i. Very coarse (#8): All particles pass through sieve

no.8 and not more than 20% through sieve no.20

ii. Coarse (#20): All particles pass through sieve no.20

and not more than 40% through sieve no.60

iii. Moderate (#40): All particles pass through sieve

no.40 and not more than 40% through sieve no.60

iv. Fine (#60): All particles pass through sieve no.60

and not more than 40% through sieve no.80

v. Very fine: All particles pass through this sieve.

There is no limits as greater fineness.

Mixing of powders

• Ingredients of powder should be mixed

thoroughly using the technique of doubling-up

to insure an even distribution(some times

called geometric dilution).

• This process involves starting with ingredient

which has smallest bulk.

• The other ingredients are added progressively

in approximately equal parts by volume.

• In this way the amount in the mortar is

approximately doubled at each addition.

Mixing of powders

• Mixing in b.w additions continues

until all the ingredients are

incorporated. The powder can then be

packed.

Method of preparation

1. Reduction of particle size of all

ingredients to the same range to prevent

stratification.

2. Sieving.

3. Weighing of each ingredient.

4. Mixing.

5. Packaging.

(a)General method for preparation of

bulk powders:

1. Weigh the powder present in smallest

volume (powder A) and placed in

mortar.

2. Weigh the powder present in the next

largest volume (powder B) and placed

on labeled weighing paper.

3. Add approximately same amount of

powder B as powder A in the mortar.

Cont.

4. Mix well with pestle.

5. Continue adding amount of powder B

that is approximately the same as that in

the mortar and mix with the pestle, i.e

doubling the amount of powder in the

mortar at each addition.

(b)General method for preparation

of divided powders:

1. The minimum weight of individually wrapped

powder is 120mg.Dilution of drug with a

diluent usually lactose is often necessary to

produce this weight.

2. Usually tablets or capsules may be used to

prepare oral powders . This involves either

crushing the tablets in a mortar and pestle, or

emptying the contents of the capsule and

adding a suitable diluent.

Cont.

3. Lactose is most commonly used diluent

because it is colourless, odourless,

soluble and is generally harmless and

has good flow properties.

4. Some patients may be unable to tolerate

lactose and a suitable inert alternative

diluent, for instance light kaolin, would

then be used.

Powder calculations

• Always calculate for at least 1 extra powder to

compensate loss of powder during

manipulations.

• If amount of active ingredient is less than

minimum weighable quantity than dilutions

(triturations) are to be made.

• Min. weighable quantity is diluted over several

time to obtain requested dose.

While dealing powders calculations

Powder calculations:

A. Doubling up method

B. Calculations involving powder volumes

Example: E.g.

Rx

Hyoscine HBr 300 mcg

mitte 4 powders

one to given 30minutes before journey

(Remember: minimum powder weight for divided

powder = 120mg)

Calculate for 5 doses

Active req. = ?

Diluent (lactose) req. = ?

Powder calculations:

• Step-1

• Hyoscine HBr =100mg

• Diluent =900mg

• Step-2

• Triturate A =100mg

• Diluent =900mg

• Step-3

• Triturate B =?

• Diluent =?

Folding of paper

It involves following steps:

1. The long edge away from the dispenser should be turned over to about one-7th of the paper width.

2. The powder should be weighed accurately and placed on the paper towards the folded edge of the centre of the paper.

3. The unfolded long edge should then be brought over the powder to meet the crease of the folded edge and the flap closed over it.

Folding of paper

4. The folded edge should then be folded over(towards the dispenser)so that it covers about half the powder packet.

5. The short edges of the powder packet should be folded over. using a powder cradle if available, so that flaps are of equal lengths and the folded powder fits neatly into a box a jar. Before making these folds ensure that there is no powder in the ends to be folded, otherwise it may fall out and be lost.

Folding of paper

Advantages of powders:

1. Good chemical stability compared with fluids

2. useful for bulky drugs with large dose, e.g.

indigestion powder.

3. Easy to swallow even in large bulk, especially

if mixed with drink food (useful for stomach-

tube feeding)

4. The smaller particle size of powders causes

more rapid dissolution in body fluids,

increases drug bioavailability, and decreases

gastric irritation compared with tablets.

Advantages of powders:

5. Faster dissolution rate/Bioavailability

6. Rapid onset of action

7. Can be taken orally by some patients

who are unable to swallow other solid

dosage forms such as capsules and

tablets.

Disadvantages of powders:

1. Not suitable for drugs unstable in

atmospheric conditions

2. Not suitable for bitter, nauseating,

deliquescent and corrosive drugs.

3. Inaccuracy of dose in case of bulk

powder

4. Inconvenient to carry.

Shelf life and storage of internal

powders

1. Shelf life of internal powders is 2-4

weeks.

2. Proprietary powders often have a longer

shelf life because of protective

packaging.

3. Storage for these powders should be

moisture proof and airtight.

Shelf life and storage of external

powders

1. Shelf life of external powders is 4

weeks.

2. Dry powders should remain stable for

long period of time if packaged and

protected from atmosphere.

3. Store in a cool and dry place.

Containers for internal powders

• Extemporaneously prepared individually

wrapped powders are often dispensed in a

paperboard box.

• It is preferable to use a screw-top glass or

plastic container which provides an air

tight seal and protection against moisture.

• Bulk powders are packed in an airtight

glass or plastic jar.

Containers for internal powders

Containers for external powders

• Powders for external use may be packed

in glass, metal or plastic containers with a

sifter-type cap. Some are also available

commercially in pressurized containers,

containing other excipients such as

propellant and lubricants.

Containers for external powders

Labels and advice for internal

powders

• Powders are usually mixed with water or

another suitable liquid before taking,

depending upon their solubility.

• Powders for babies can be placed directly

into mouth followed by a drink to wash

down the powder.

• Bulk powders should be shaken and

measured carefully before dissolving in a

little water and taking.

Labels and advice for internal powders:

Labels and advice for external powders

• For external use only.

• Store in cool ,dry place.

Labels and advice for external powders:

Uses of powders:

• Powders are used as counter-irritant e.g

/camphor starch dusting powder.

• Rhubarb powder is used in dyspepsia.

• Chlorhexidine dusting powder is used as

antimicrobial.

• Dover’s powder( ipecacuanha and opium)

is used as antipyretic.

• Magnesium trisilicate powder is used as

antacid and anti-flatulent.

Uses of powders:

• Powders are also used as antiseptics.

Uses of powders:

• Ibuprofen powder is used to treat juvenile

arthritis.

• Rumford is used as aluminium free

baking powder.

Uses of powders:

• Powders are also used in cosmetics as

face powders.

Uses of powders:

• Prickly heat powders are used to relief

skin burn.

Uses of powders:

• Baby powders are used to protect skin

and nappy rashes.

Granules

TOPIC CONTENTS:

Granules: • a)Introduction

• b) Classification

• c)Method of preparation

• d)Advantages and disadvantages

• e)Shelf life and storage

• f)Containers

• g)Packaging

• h)Labeling

• i)Pharmaceutical uses

Introduction

• Granules are powder agglomerated to produce

large free flowing particles.

• Granules are particles ranging in size from

about 4 to 10 mesh.

• They are irregularly shaped but may be

prepared to be spherical.

• Granulation are also used as intermediates in

the preparation of capsule and tablets, since

they flow more smoothly and predictably than

do small powder particles.

Granules

Why we prepare granules when we have

powders?

1. To avoid powder segregation.

2. To enhance the flow of powder.

3. Granules have higher porosity than

powders.

4. To improve the compressibility of

powders.

5. Materials, which are slightly

hygroscope, may adhere & form a cake

if stored as a powder.

Classification

Granules are classified into following

categories:

1. Effervescent granules.

2. Coated granules.

3. Gastro-resistant granules.

4. Modified release granules.

1: Effervescent granules

• Effervescent granules are uncoated

granules generally containing acid

substances and carbonates or hydrogen

carbonates which react rapidly in the

presence of water to release carbon

dioxide.

• They are intended to be dissolved or

dispersed in water before administration.

Effervescent granules

2: Coated granules

• Coated granules are usually multi-dose

preparations consist of granules coated

with one or more layers of mixtures of

various excipients.

• The substances used as coatings are

usually applied as solution or suspension

in conditions in which evaporation of the

vehicle occur.

Coated granules

3: Gastroresistant granules

• These are delayed release granules that

are intended to resist the gastric fluid and

to release the active substance in

intestinal fluid

• These properties are achieved by

covering the granules with the gastro-

resistant material or by other suitable

means.

Gastro-resistant granules

4: Modified release granules

• They are coated or uncoated granules

which contain special excipients or which

are prepared by special procedure are

both , designed to modify the rate , the

place or the time at which the active

substance or substances are released.

• Modified release granules include

prolonged release granules and delayed

release granules.

Modified release granules

Advantages and Disadvantages of granules

Advantages

1. Granules are more flowable compared to powder.

2. Segregation of the constituents of the powder mixture could be avoided by granulation.

3. Granules are more stable against humidity and atmosphere.

4. Granules are more easily wetted by liquids than light and fluffy powders.

Disadvantages

1. The masking of bitter tastes may be a problem with this type of preparation.

2. Granules are not a good method of administering potent drug with low dose.

3. Instability in presence of moisture.

4. Problems in packaging and storage.

Methods of preparation

Granules are generally prepared by two

methods.

1) Wet method

2) Dry method

Wet method:

• Wet method is to moisten the powder or

powder mixture and then pass the

resulting paste through a screen of the

mesh size to produce the desired size of

granules.

• The granules are placed on drying trays

and are dried by air or under heat.

• The granules are periodically moved

about on the drying trays to prevent

adhesion into a large mass.

Wet method:

• Another type of wet method is fluid bed

processing, in which particles are placed

in a conical piece of equipment and are

vigorously dispersed and suspended

while a liquid excipient is sprayed on the

particles and the product dried, forming

granules or pellets of defined particle

size.

Fluid bed processing:

Dry method:

Dry granulation is performed by two

ways.

a) Roll compactor

b) Slugging

a) Roll compactor:

• Dry powder is passed through a roll compactor

and then through a granulating machine.

• A roll compactor, also called a roll press or roller

compactor, processes a fine powder into dense

sheets or forms by forcing it through two

mechanically rotating metal rolls running counter

to each other .

• The surface of the compacting rolls may be

smooth or may have pocket indentations or

corrugations that allow compaction of different

forms and textures.

Cont..

• The compacted powder is granulated

to uniform particle size in a

mechanical granulator. Powder

compactors are generally combined

in sequence in integrated compactor–

granulation systems.

a) Roll compactor:

b) Slugging:

• Slugging, is the compression of a powder

or powder mixture into large tablets or

slugs on a compressing machine under

8,000 to 12,000 lb of pressure, depending

on the physical characteristics of the

powder.

• The slugs are generally flat-faced and are

about 2.5 cm (1 inch) in diameter.

Cont.

• The slugs are granulated into the desired

particle size, generally for use in the

production of tablets. The dry process

often results in the production of fines,

that is, powder that has not agglomerated

into granules. These fines are separated,

collected, and reprocessed.

Preparation of effervescent granules:

These granules are prepared by two

methods:

A) Fusion method

B) Wet method

A) Fusion method:

• In the fusion method, the one molecule of

water present in each molecule of citric acid

acts as the binding agent for the powder

mixture.

• Before mixing the powders, the citric acid

crystals are powdered and then mixed with the

other powders of the same sieve size to ensure

uniformity of the mixture.

• The sieves and the mixing equipment should

be made of stainless steel or other material

resistant to the effect of the acids.

Cont.

• The mixing of the powders is performed as rapidly as

is practical, preferably in an environment of low

humidity to avoid absorption of moisture and a

premature chemical reaction.

• After mixing, the powder is placed on a suitable dish

in an oven at 34°C to 40°C.

• During the heating process, an acid-resistant spatula

is used to turn the powder.

• The heat releases the water of crystallization from

the citric acid, which, in turn, dissolves a portion of

the powder mixture, setting the chemical reaction and

consequently releasing some carbon dioxide.

Cont.

• This causes the softened mass of powder to

become somewhat spongy, and when it has

reached the proper consistency (as bread dough),

it is removed from the oven and rubbed through a

sieve to produce granules of the desired size.

• A No. 4 sieve produces large granules, a No. 8

sieve prepares medium size granules, and a No.

10 sieve prepares small granules.

• The granules are dried at a temperature not

exceeding 54°C and are immediately placed in

containers and tightly sealed.

B) Wet method:

• The wet method differs from the fusion method in

that the source of binding agent is not the water of

crystallization from the citric acid but the water

added to alcohol as the moistening agent, forming

the pliable mass for granulation.

• In this method, all of the powders may be

anhydrous as long as water is added to the

moistening liquid.

• Just enough liquid is added (in portions) to

prepare a mass of proper consistency; then the

granules are prepared and dried.

Example:

• Sodium citrate and tartrate B.P.

• Ingredients Quantity

1) Sodium bicarbonate 510gm

2) Tartaric acid 270gm

3) Citric acid 180gm

4) Sucrose 150gm

Shelf life and storage:

• Shelf life of granules is 2-3 weeks.

• Granules should be stored in airtight

containers.

• Granules should be placed at cool and dry

place.

Container

• Granules should be kept in air tight container.

Container:

Label and advice

• Dissolve or mix with water before taking.

• A normal dose is 1-5 g of the powder

taken in liquid, when required.

• Antacids are usually taken before meals

and at bedtime.

Label and advice:

pharmaceutical uses:

• Effervescent granules are used as an antacid.

pharmaceutical uses:

• Methylcellulose granules are used as a

laxative.

Uses of granules:

• Granules are also used in fertilizer industry.

Uses of granules:

• Granules are used for instant preparation of

solutions and suspensions.

Uses of granules:

• Lactinex granules are used in uncomplicated

diarrhea.

Uses of granules:

• Granules are also used as animal foods.

9- Relatively simple method of processing/formulation

Powders 1- Comparatively poor flow properties

Granules

1- Flow well compared to tablets, good

2- Has less surface area, more stable to atm. effect

3- Less likely

4- More easily wetted by the solvents, good choice reconstitution liquids

5- Good compressibility

6- Relatively more uniformity of contents in case of granules

7- Generate less dust on handling

8- Have a more elegant appearance

9- It involves more processing, exposure to heat and contact with solvents

2- Relatively less stable (physically and Chemically) due to inc. S.A & Atm. Effect

3- More likely to hardening / cake formation on long storage

4- For some powders, drugs float on the surface, difficult to make solution

5- Relatively poor compressibility

6- Chances of non uniform dosing are more

7- More dust due to small particle size

8- Comparatively less appealing

Powders VS Granules

Thank You