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Introduction to Pharmaceutics-1

PCT 221
3rd Semester
)

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Unit-1
Unit-2
Unit-3
Unit-4
Unit-5

Powders and Granules


Semisolid Dosage Forms
Emulsions
Suspensions
Pharmaceutical Calculations

Total Credit = 3
Assessment
= 2CAs(60%) + End of sem.
Exam
(40%)
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Recommended Books
1. Pharmaceutical dosage forms and drug delivery systems
Ansel H.C, Popovich
2. Pharmaceutics, The science of dosage form design, M.E
Aulton
3. Remington, The science and practice of Pharmacy Vol-1 & 2
4. Pharmaceutical Calculations by Stocklosa & Ansel
5. Any other handouts / Reference material given to the class

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Unit-1
Powders and Granules

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Unit contents
1. Powders and granules as dosage forms
2. Special problems in powdered dosage
forms
3. Factors affecting drug availability from
powdered dosage forms
4. Package and storage of powders

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TOCs
Basic definitions
Advantages and disadvantages
Powders and granules as dosage forms
(types / Differences)

Special problems in powdered dosage forms / Solution


Factors affecting drug availability from Powdered DF
Packaging and storage
Particle size and size analysis
Calculations
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Definitions
Micromeritics:
Science of small particles

Powders:
Is a mixture of finely divided drugs and /or Chemicals in a dry
form
According to B.P = subdivided solids containing constituent
particles which can range 1.25um 1.7mm in diameter
As DF = are formulations in which powdered drug has been
mixed with powdered excipients to produce final formulations
Eg. Oral powders, Dusting, dentifrices, bulk powders etc

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Granules

(Sieve size=4-12)

Are aggregations of fine particles of powders in


a mass of about spherical shape or
Consists of powdered particles which have
been aggregated to form a larger particles of
about 2-4mm in diameter
Can be prepared by
Dry or
Wet Granulation techniques

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Why we prepare granules when we have


powders?
1. To avoid powder segregation,
if the powder is composed of particles with
different dimensions & different densities, a
separation between these particles will occur.

2. To enhance the flow of powder,


Higher flow ability gives better filling of the dies or
containers, during a volumetric dosage.
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3. Granules have higher porosity than powders,


4. To improve the compressibility of powders.

5. The granulation of toxic materials will reduce


the hazard of generation of toxic dust, which
may arise during the handling of the powders.

6. Materials, which are slightly hygroscope, may


adhere & form a cake if stored as a powder.
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Sieve Number
A number used to designate the size of the Sieve,
which corresponds to the no. of openings per linear
inch
E.g.. Sieve 20 will have 20 openings in 1 linear
inch

Sieve opening
Its an approximate size of aperture of a given sieve
as given in USP
E.g. sieve no 20 will have 20 opening per linear
inch and each opening will have an aperture size =
850m
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Some commonly used sieve no

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Sieve Number

Sieve opening
(m)

20

850

40

425

60

250

80

180

120

125

..

..

400

38

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Angle of repose ( = Tan-1 h/r)


The maximum slope measured in degrees from
the horizon at which loose solid material will
remain in place or
Angle of repose of a granular powder is the
steepest angle of descent or dip relative to
horizontal plan to which a material can be piled
up.
If > 50 unsatisfactory flow
= 25 or less than 25 very good flow
properties
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Glidents
Excipients that increase flow properties of
given material By correcting surface
irregularity, reducing friction or by neutralizing
surface charges b/w particles
E.g.,

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Mag. Stearate,
Aerosil (colloidal silicon dioxide),
Starch,
Talc

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Geometric mixing/dilution

(doubling up method)

Mixing of ingredients according to order of their


increasing weight/volume in equal proportions
E.g.
A
B
C
D

Consider the following master formula


=10g
=50g
=40g
=90g

What could be the benefits ?


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Powder mixing techniques


Spatulation
is the combining of materials (2 or more powders) into a
homogeneous mixture by continuously mixing them together
& smoothing the mass out on a smooth surface with a
spatula

Trituration
is the process for reducing the particle size of a substance
by grinding, eg grinding of powders in a mortar with a pestle

Sifting
relates to putting through a sieve or straining device to
separate fine particles from coarse ones

Tumbling
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Advantage of powders/granules
1. Stability
Solid are more stable than liquids
E.g. (Ampicillin)
Antibiotics powders dry form = 2-3 yrs shelf
life
While liquid of same antibiotics = 1-2 weeks

2. More suitable/convenient DF for large


dose
E.g. Mag.Trisillicate Antacid (1-5g)

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3. Faster dissolution rate/Bioavailability


Increase S.A ------- increase dissolution
Rapid onset of action

4. Can be taken orally by some patients


who are unable to swallow other solid
dosage forms such as capsules and
tablets
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Disadvantages
Inconvenient to carry / handle
(except when presented as divided DF)

Unpleasant Taste
Not very suitable DDS for potent drugs
Divided DF can be used however Tabs are
preferred

Not suitable for acid labile / Enzyme prone


drugs (Coated granules may be used)
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Disadvantages. (Cont.)

Poor/Misunderstanding about correct


method of use
Higher decomposition rate incase of
Hygroscopic, deliquescent or aromatic
ingredients

Because of different particle size/density


diff. powder mix can be partly separated.
Non uniform distribution
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Powders VS Granules
Powders

Granules

Comparatively poor flow properties

Flow well compared to tablets,


good choice for compressing tabs

Relatively less stable (physically


and Chemically) due to inc. S.A &
Atm. Effect

Has less surface area, more stable


to atm. effect

More likely to hardening / cake


formation on long storage

Less likely

For some powders, drugs float on


the surface, difficult to make
solution

More easily wetted by the


solvents, good choice
reconstitution liquids

Relatively poor compressibility

Good compressibility

Chances of non uniform dosing are


more

Relatively more uniformity of


contents in case of granules

More dust due to small p.s

Generate less dust on handling

Comparatively less appealing

Have a more elegant appearance

Relatively simple method of


processing/formulation

It involves more processing,


exposure to heat and contact with
solvents

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Preparation of Granules
Wet method
Moistening the desired powder
Passing paste like mass thru sieve no 4-14.
Tray dry / oven dry / vacuum dry
Packed and labeled

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Dry method
Powder material is passed through a roll
compactor
Granulating machine.
Densified sheets or flakes
The compacted powder is then granulated to
uniform particle size by passing through a
mechanical granulator.
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Powders and granules


as dosage form.

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Therapeutic use:
As a true & proper
pharmaceutical
dosage form

Bulk/divided/
dusting/insu
fflations/DPI/
Reconstitutio
n

Non therapeutic
use:
for the preparation
of other dosage
forms

Tablets,
Capsules,
Suspensions,
Solutions etc

Powders /
Granules

All powders are


stored at dry place
Away from children
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Bulk Powders
Mixed ingredients are packed suitable
containers like wide mouthed bottles or
glass jars
Constituents are non toxic / Less potent
Large doses can be dispensed
Usually supplied with a measuring spoon
Proper directions for use should be provided

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Bulk Powders (Cont)


E.g.

Compound Mag Trisilicate powder


Refreshens salt (laxative)
Douch powders for vaginal irrigation/ cleansing
Dietry suppliments and feeding formula.

STORAGE: wide mouthed bottles, plastic /


glass, Cool and dry place, out of children reach

Prepare a list of at least 3 bulk powders


available in Botswana,
Ingredients, Uses, type of packaging etc.
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Bulk Powders (Cont)

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Divided powders
More potent ingredients are usually
packed individually/ separately wrapped.
List advantages / Disadvantages

E.g.

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Mag. Trisilicate powder individually wrapped


Grand Pa , (?)
Acetyl cystine
List some more with ingredients (check
Community Pharmacy)
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Divided powders (Cont)

Packaging
Ind. Wrapped paper, (How to wrap)
If material is volatile or moisture sensitive than
wax lined paper or grease proof paper
Air tight sealed sachets
Foiled laminate (replaced Paper)
Individual powder are than boxed. (easy
handling)

Storage
Cool and dry place, Avoid moisture (avoids
agglomerates formation)
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Divided powders (Cont)

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Dusting Powders.
Used externally for
Therapeutic ---- antifungal
Prophylaxis----- antifungal/antiseptic
Lubricating------ talc, Kaolin etc
Dusting powders for open wounds should be
sterile (chlorohexidine Dusting Powders), but lubricating
powders do not need to be sterilized, however
should be free from pathogens/Spores,
Dry heat for sterilization is usually used,,
for more than 60 minute)
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(1600C

Dusting Powders.(Cont)

Packaging,
Plastic, Glass or metal drum fitted with a perforated
lid.
Glidents are usually added to enhance the flow
(Talc, Sterillizable Maiz starch)

Storage:
Closed Lid, Dry place, Away from child..

Examples
Antifungal/ Antibacterial foot powders.
Zinc undecylinate, Chlorohexidine
Lubricating dusting powder,
Talc
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Insufflations
Are medicated powders intended to be blown into
regions such as ear, nose, and throat with the help of
an insufflators
Not very acceptable, In-elegent and less convenient
to use,
May show systemic effects (Rapid abosrption)
Some drugs are more rapidly absorbed from lungs
than oral use. E.g. Sodium Chromoglycolate
Traditional insufflator replaced by Advance devices,
Handihaler,
Accuhaler, Etc.
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Dry powders for inhalation (DPIs)


DPIs are used to deliver medicaments to lungs in a
dry powder form using a hand-held device, as you
inhale through it.
It does not have propellant like MDI do.
E.G
Seretide Accuhaler,
(Can you list what does serretide contains)

Handihaler
Uses a capsule in device which is broken down as you
operate and than u inhale medicaments.
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FDA approved Afrezza

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(Insulin DPI)

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Video Demonstration

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For optimum delivery and absorption into


the lungs,,,,,,,, What should be the Particle
size
????

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If particle size is less than 0.5 micron, than drug may be


exhaled out with breath when given as powdered DF...

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Oral antibiotics powders


Reconstituted at the time of use.
Moisture can cause degradation of the
product, So presented as dry powder for
reconstitution
E.g.
Phenoxy methyl peicillin.
Cefaclor,
Augmentin
List more
Shake well before use for suspension

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Powder for injections (PFI)


Sterile powders in ampoule / Vials
Must be made immediately before use
Diluents WFI
Contains other additives along with active
moiety

E.g.
Augmenting PFI
Amphoteracin B, Ampicillin, Ceftriaxone PFI
Cephradine, and chloramphenical PFI

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Special problems in
Powdered DF / Solution

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Volatile substances
Such as
Camphor, menthol, essential oils
Evaporation loss.

Solution
Packed into heat sealed plastic bags,
Air tight containers
Proper storage instructions to the client

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Eutectic mixture
Some solids when mixed together form liquid.
E.e. Phenol, menthol, thymol, antipyrene,
phenacetin.

Solution.

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Adding inert diluents such as


Mag. Carbonate
Light Mag oxide
Kaoline,
Starch,
Bentonite
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Liquids
Can be added in small amounts to
powders.
Some adsorbing materials should be added.
Lactose,
Mag.Carbonate, Starch.

Fluid extract & Tinctures used in this way

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Hygroscopic or Deliquescent material


Absorb moisture from air and liquefy
Increase rate of hydrolysis

Packed in air tight containers.


Inert diluents can be added.

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Efflorescent materials
Crystalline substances may liberate water
of crystallization due to trituration and
powder becomes wet.
Anhydrous salt form can be used.
Inert diluents can be added.

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Factors affecting
Drug availability
from Powdered DF
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Some basic concepts

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Particle size can influence a number a


factors
Dissolution rate
Suspendability
Uniform distribution
Penetrability
Texture of the formulation
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Dissolution
Process by which a drug particle dissolves

Noyes Whiteny
Equation

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Surface area
Particle size is inversely related to S.A
Poorly or slowly soluble drugs when presented
in small particle size enhanced
dissolution enhanced bioavailability
E.g.
Theophyllin,
Griseofulvin

Micronized powder in SDF show more rapid


absorption
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Crystal or amorphous form


Amorphous form of a chemical is more
soluble than its crystalline counterpart.
E.g.
Chloramphenicol is ineffective in its
crystalline form but show good absorption
through GIT in its amorphous state

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Salt form
Drugs are either week acid or week basis.
Sodium and potassium salts of week organic acids
&
Hydrochloric salts of week organic basis
SHOW

Rapid dissolution rate than respective


free drugs
E.g.
EthyleneDiAmine salt of Theophyyline has 5-Fold
water solubility
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Sate of hydration
Anhydrous form of an organic molecule is
more soluble than its hydrated counter
part.
E.g.
Ampicillin Anhydrous is more soluble than its
tri-hydrate form

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Effect of pH
Unionized form of drug absorb more faster
than ionized form.
Week acidic drugs absorb well in acidic pH.
i.e Stomach
Basic drugs absorb well in intestine.

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Particle size and Size


distribution analysis

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Particle size and Size distribution analysis


A number of methods can be used including
1. Microscopy

Calibrated grid background

2. Sieving
3. Sedimentation rate

Terminal settling velocity

4. Light energy diffraction

Reduction of light reaching the sensor

5. Laser holography
3D picture by holography camera
6. Cascade impact

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Striking surface with air stream


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Sieving technique
Sieve number ?
Sieve Opening ?
Principle
Particles passed by mechanical shaking through
a series of sieves of known sizes (which reduces
gradually from top to bottom),
Amount of powder retained / Passed through is
determined and manipulated
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Sieves are usually made up of wired cloth


woven from
Brass,
Bronze or other metals

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Sieve No.

Sieve
Opening
(m)

20

850

40

425

60

250

80

180

120

125

..

400

38

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USP characterize Powders by following


descriptive terms

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Type of powder

All particles
pass thru Sieve
No

Not more
than

Very coarse

20% thru 60

Coarse

20

40% thru 60

Moderately
coarse

40

40%thru 80

Fine

60

40% thru 100

Very fine

100

No limit

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Powders calculations

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While dealing powders 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 qty than dilutions
(triturations) are to be made
Min. weighable qty is diluted over several time
to obtain req. dose
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A. Doubling up method / Trituration


B. Calculations involving powder volumes

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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. = ?
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Step-1
Hyoscine HBr =100mg
Diluent =900mg

Step-2
Triturate A =100mg
Diluent =900mg

Step-3
Triturate B =?
Diluent =?
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Example
Rx
Send 10 aspirin powders 200mg for a
child
of 3-years (14kg)
Is dilution required?
300 mg tabs are available in dispensary

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Example
Calculate quantities required to make 8
powders each containing 200mcg of digoxin
per 120 mg of powder.
Use lactose as a diluents
Min. weighable qty = 100mg (class B
balance)

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Calculation involving powders volume


Powder displacement
Example

a) Calculate the volume of suspension


occupied by amoxicillin powder
150mL 111mL = 39mL

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b) Quantity of amoxicillin present in entire


bottle

5mL contains
150mL contains

=250mg
=7500mg

c) Volume of suspension that will contains


500mg/5mL

7500mg /500mg/5mL

=75mL

d) Volume of purified water required

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75mL-39mL

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=36mL of water to be added.

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If the volume of 250mg of ceftriaxone


sodium (powdered) is 0.1mL. How many
mL of diluents should be added to 500mg
of ceftriaxone to make 250mg / mL
concentrated suspension.
Volume of ceftriaxone ?
Final volume of product.?
Volume to be added.?

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Some practice problems

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