Assist. prof. Dr.

Ahmed Alsaad

LIQUID DOSAGE FORMS

Dosage forms are essentially pharmaceutical products in the form
which involves a mixture of active drug components and nondrug
components (excipients). Liquid form of a dose of a drug used as
a drug or medication intended for administration or consumption.

Liquid dosage forms are prepared:

a. By dissolving the active drug substance in an aqueous or non-
aqueous (e.g. alcohol, ether, glycerin) solvent,
b. By suspensing the drug in appropriate medium, or
c. By incorporating the drug substance into an oil or water
phases.
2
ADVANTAGES OF LDF
Advantages:
a. Better for patients who have trouble swallowing expiration than
other.
b. Faster absorption than solids.
c. More flexibility in achieving the proper dosage of medication.
d. Palatable.
e. Best choice for children and old age person.
3

DISADVANTAGES OF LDF

a. Shorter life than other dosage form,

b. Harder to measure accuracy,
c. Need special storage condition.
d. Less stable,
e. Easily affected by microorganisms,
f. Bulky to carry around.
g. Easy to loss by the breakage of the container.
h. Measuring dose is required.
4
ADMINISTRATION OF LDF

Liquid dosage forms can be administered:

a. Topically - lotions or suspension applied to the skin, nasal
drops, ear drops, eye solutions.
b. Orally (p.o.) – oral suspension, emulsion & solution.
c. Parenterally -
 subcutaneous injection (s.c.),

 intramuscular injection (i.m.)

 intravenous administration (i.v.)

6
 Monophasic Liquid Dosage Forms

Liquids meant for internal Liquids meant for external

administration administration

Syrups

Mixtures
Liquids applied to Liquids used in Liquids instilled
the skin mouth into body cavities
Elixirs
Lotions Gargles Douches
Linctuses
Liniments Ear drops
Mouthwashes
Collodions Nasal drops
Paints Throat paints
Eye drops
Enemas

Syrup Elixirs
Concentrated aqueous Clear, aromatic,
preparations of 60% to sweetened hydroalcoholic
85% sucrose with or solutions with or without
without flavoring medicinal substances,
agents and medicinal intended for oral use.
substances. eg:Dexamethasone elixir
e.g. Chlorpheniramine (Medicated)
maleate syrup, Compound benzaldehyde
Chloral hydrate syrup elixir (Non-medicated)
etc Liquids meant
for internal
administratio
Mixture ns
Liquid preparation Linctuses
meant for oral Viscous, liquid and
administration in oral preparations
which medicaments that are generally
are dissolved in a prescribed for the
suitable vehicle. relief of cough.
Eg: Orange peel Eg: Codeine Linctus. 8
infusion
Liquids meant for external administrations
Mouthwash
Gargles
Aqueous solutions Aqueous solution with
containing antiseptics, a pleasant taste and
antibiotics or odor used to clean and
anesthetics used to deodorize the buccal
prevent or treat throat cavity. Have antiseptic
infections. and astringent
Available in activity.
concentrated form with eg: Antiseptics-phenol
direction for dilution derivatives
with warm water before Astringents-Zinc
use. a) Liquids Chloride
eg:Phenol gargle used in the
mouth
Throat paints
Throat sprays
Viscous liquid
sprayed into the
preparation used for
throat are
mouth and throat
intended to
infections.
medicate the
Eg:Phenol glycerine,
lungs 9
Compound Iodine
paint

Liquids meant for external administrations

Enemas
Douches Aqueous or oily
Medicated solution that is
solution meant introduced into the
for rinsing a body rectum and colon via
cavity as eyes, ear Nasaldrops
the anus for
or nasal cavities Administered
cleansing,
for cleaning or through the nose to
therapeutic or
removing the obtain a systemic or
diagnostic purposes
foreign particles local effect. Used for
or discharge from symptoms such as
b) Liquids nasal congestion
them. Eg: isotonic
instilled caused by an
sodium chloride
into body allergy, or a related
solution
cavities upper-respiratory
Otic Eye drops problem.
preparations Sterile,aqueous/ Eg:Beclomethasone
Applied to or in oily solutions dipropionate nasal
the ear to treat or intended for drops
prevent dermatitis instillation in
of the ear, eyeball.
cerumen build up Eg:Moxifloxacin 10
and ear infection. eye
Eg: soda glycerine drops
 Liquids meant for external administrations
Collodions
Highly flammable syrupy Liniments
solution of pyroxylin Alcoholic and oily liquid
dissolved in ether and preparations
alcohol, which dries to a Intended for external
clear tenacious film application with rubbing
Used as a topical to the affected area
protectant to close small Topically used to relieve
wounds, abrasions and pain and stiffness, such
cuts as from sore muscles or
to hold surgical dressings from arthritis.
c) Liquids
in place Lotions
meant for
Either liquid or semi-
external
liquid preparations that
Paints use (Skin)
contain one or more active
Solutions used ingredients in an
to sterilize the appropriate vehicle.
skin. Topical preparation with a
Eg. Crystal low to medium viscosity
violet , Magenta Intended for application to
paint unbroken skin without 11
friction.
Eg: Calamine Lotion,

Pharmaceutical Solutions

Aqueous Sweet &/or Nonaqueou

Viscid s
1. Douches
2. Enemas 1. Syrups 1. Elixirs
3. Gargles 2. Honeys 2. Spirits
4. Mouthwashes 3. Mucilages 3. Collodions
5. Nasal washes 4. Jellies 4. Glycerins
6. Juices 5. Liniments
7. Sprays 6. Oleo
8. Otic solutions Vitamin
9. Inhalations 12
Syrup

13

14
15

16
 ADVANTAGES OF SYRUP
 Appropriate for any patient, whatever the age is
 The most natural and easiest route of administration

 Economical and safe to the patient

 No nursing is required, which means the patient can take

it with no help
 The liquid dosage form is expected for certain types of
products like cough medicines
 Suitable for water soluble stable drugs

 Self preservatives if having density 1.313

17

DISADVANTAGES OF SYRUP
 Delayed onset of action because absorption takes time
 Not suitable in emergency and for unconscious patients

 Not convenient for a patient with a gastrointestinal

disorder such as diarrhea, constipation, ulceration, and
hyperacidity in stomach
 Not suitable for diabetic patients

 Pleasant taste – children take more dose

 If sucrose content is not proper – prone to microbial

growth
 Highly concentrated syrup get crystallized if other
substances like glycerin, sorbitol not added. 18
COMPONENTS OF SYRUP
Most syrups contain the following components in addition
to the purified water and any medicinal agents present:
(a)Sweetening Agent- the sugar, usually sucrose, or sugar
substitute used to provide sweetness and viscosity
(b) Antimicrobial Preservatives
(c) Viscosity Modifier
(d) Flavorants
(e) Colorants
many types of syrups, especially those prepared
commercially, contain special solvents, solubilizing agents,
thickeners, or stabilizers. 19

PREPARATION OF SYRUP
There are four methods. Based on the physical and
chemical properties on the ingredients, the choice of the
method is selected-

I. Solution with heat

II. Agitation without heat
III. Addition of sucrose to liquid medicament
IV. Percolation method

20
1. Solution with heat-
temperature of purified water is increased to 80 to 85 C

taken off from the heat source

Then add sucrose and shake it thoroughly

Those substances that are heat sensitive and volatile agents

are added after the solution attain the room temperature

during heating, the sucrose gets hydrolysed, results in the

formation of dextrose and fructose

these two sugars together called as invert sugar and the

process is known as inversion
21
The inversion leads to darkening of the solution

2.Agitation without heat-

vessel is taken generally made up of stainless steel or glass

The vessel should be larger than the desired volume of syrup

required

Then the ingredients according to the formulation are added

to water and mixed

It is better to dissolve solid ingredients in the water first and

then to add them to syrup

This results in easy mixing as sugar solution generally retards

mixing 22
 3. Addition of sucrose to liquid
medicament-
This method is generally used for fluid extracts.

But those substances which are soluble in alcohol will

precipitate out as soon as the addition of water

An alternation is to first dissolve all the ingredients in water

Now after sometime all the precipitates formed are filtered

out

Now add sucrose

But this method is of no use if the precipitates formed has

active ingredients
23

3. Percolation

In this method, either sucrose maybe percolated to prepare the syrup or the
sucrose of the medicinal component may be percolated to form an extractive to
which sucrose or syrup may be added.

Procedure:

Purified water or aqueous solution of a medicating or flavoring liquid is

allowed to pass slowly through a column of crystalline sucrose to dissolve it.

24
 2. The percolate is collected and returned to the percolator as required until all
of the sucrose has been dissolved.

3. Percolator with a pledget of cotton at the bottom is used

Example: Tolu Balsam syrup - flavor for cough syrup

4. Addition of Sucrose to a Medicated liquid or to a Flavored liquid

Occasionally, a medicated liquid, as a tincture of fluidextract is employed as the

source of medication in the preparation of a syrup.

Many such tinctures and fluidextract contain alcohol-soluble constituents and are
prepared with alcoholic vehicles.

Examples: Senna Syrup, NF and Cherry Syrup

25

Preservation of Syrups
 The USP suggests that syrups be kept at a temperature
not above 25°C.
 Preservatives such as glycerin, methyl paraben, benzoic
acid and sodium benzoate may be added to prevent
bacterial and mold growth, particularly when the
concentration of sucrose in the syrup is low.
 The concentration of preservative is proportional to the
free water.
 The official syrups should be preserved in well dried bottles
and stored in a cool dark place.

26
 Dextrose-Based Syrups
Dextrose may be used as a substitute for sucrose in syrups
containing strong acids in order to eliminate the
discoloration associated with inversion.
Dextrose forms a saturated solution in water at 70% w/v,
which is less viscous than simple syrup.
It dissolves more slowly than sucrose and is less sweet
Preservatives are required to improve the keeping qualities
of such syrups. Glycerin is added in 30% to 45% v/v as
preservative.

27

Artificial Syrups (Non-Nutritive Syrups)

 intended as substitutes for syrups and are to be administered
to persons who must regulate their sugar and/or calorie
intake accurately. e.g. persons suffering from diabetes
mellitus.
 Some early formulae included glycerin, however, glycerin and
propylene glycol are glycogenetic substances, i.e. they are
materials which are converted into glucose in the body.
 An example of non–nutritive syrup is ―Diabetic Simple
Syrup‖. It contains compound sodium cyclamate (6%
cyclamate sodium and 0.6% saccharin sodium)
However, the cyclamate studies showed that the sweetener could
produce cancer in animals and, as a result, this substance was
removed from a wide variety of products. Similar studies have been
carried out on saccharin. Much research has been done to find28a
safe synthetic substitute for sucrose. As a result, aspartame which
is about 200 times sweeter than sucrose, is being used now in many
commercial preparations as the sweetening agent.
Sorbitol-Based Syrups
Sorbitol which is hexahydric alcohol made by hydrogenation
of glucose has been used in the preparation of syrup.
It is used mostly in the form of a 70% w/w aqueous solution.
Sorbitol solution is not irritating to the membrane of the
mouth and throat and does not contribute to the formation of
dental carries.
Sorbitol is metabolized and converted to glucose; however, it
is not rapidly absorbed from the GlT as sugars. No
significant hyperglycemia has been found (WHY?); it may be
used as component of non-nutritive vehicles.
Sorbitol solution does not support mold growth. Preservative
should be used in solution containing less than 60% w/w
sorbitol.
29

It is chemically stable and inert with respect to drugs and

other ingredients used in pharmaceutical perpetration.

HONEYS
Are thick liquid preparations. At one time, before sugar was
available, honey was used as a base, instead of syrup.
There are few official preparations containing honey. e.g.
Oxymel, or" acid honey "'is a mixture of acetic acid, water and
honey

MUCILAGES
The official mucilages are thick viscid, adhesive liquids,
produced by dispersing gum (acacia or tragacanth) in water.
Mucilages are used as suspending agents for insoluble
substances in liquids; their colloidal character and viscosity
prevent immediate sedimentation.
Synthetic agents e.g. carboxymethylcellulose (CMC) or
polyvinyl alcohol are nonglycogenetic and may be used for30
diabetic patients.
Jellys
 Preparations having a jelly-like consistency. They are
prepared also from gums.
 Are used as lubricants for surgical gloves and catheters
 Lidocaine HCl Jelly USP is used as a topical anaethetic.

31

Medicaments commonly used:

 Antibiotics – e.g. Lincomycin HCl

 Analgesics – E.g. – Meperidine HCl

 Adrenergic – e.g. – Pseudoehedrine HCl

 Antiemetics – e.g. – Chlorpromozine HCl

 Antihistaminics – e.g. Chlorpheniramine meleate

 Antitussive – e.g. – Dextromethorphan HBr

 Iron supplement – e.g. – Ferrous sulphate

32
 SOME IMPORTANT FORMULATIONS:
 Simple syrup I.P.
Sucrose ------ 667g
Purified water to ----- 1000g
 Ferrous sulphate syrup U.S.P.

Ferrous sulphate ------- 40g

Citric acid,hydrous ----- 2.1g
Peppermint spirit ----- 2.0ml
Sucrose ----- 825g
Purified water to ----- 1000ml
33

SOME SYRUPS PRESENT IN MARKET

Brand Company Active Therapeut Use
Name Ingredient ic Class

Ambrox Square Ambroxol Cough & Cold Productive cough, Acute and
Pharmaceutica Hydrochloride Remedies chronic inflammatory disorders of
l Ltd. upper and lower respiratory tracts
associated with viscid mucus
including acute and chronic
bronchitis
Brofex Square Dextromethorph Cough & Cold Chronic dry cough/unproductive
Pharmaceutica an Remedies cough & acute dry cough which is
l Ltd. interfering with normal function or
sleep.
Tusca Square Guaiphenesin+ Cough & Cold Symptomatic relief of upper
Pharmaceutica Remedies respiratory tract disorders
l Ltd. Pseudoephedrine accompanied by productive cough.
+ 34
Triprolidine HCl
DuolaxTM Square Magnesium Laxative Constipation, Hyperacidity with
Pharmaceutica Hydroxide & constipation, Anorectal disorder.
Elixir

35

36
Advantages of Elixirs:
a. Better able to maintain both water-soluble and alcohol-soluble
components in solution.
b. Has stable characteristics.
c. Easily prepared by simple solution.
d. Used as vehicles for wide variety of potent on nauseous
medicaments.
e. Less viscous than syrups, thus do not create difficulty in
filtration operation
f. Provide flexibility and ease of dosage administration.
g. Containing over 10 to 12% alcohol are self preservative and do37
not require the addition of preservative.

Disadvantages of Elixirs:
a. Less effective than syrups in masking taste of medicated
substances.
b. Contains alcohol, accentuates saline taste of bromides
c. Less sweet and less viscous since they contain less proportion
of sugar.
d. Having high percentage of alcohol require sweetening agent
then sucrose since sucrose is slightly soluble in alcohol.
Saccharine used in preparation which has bad after taste.
e. Costlier than syrups and require many legal processing with
excise department.

38
39

40
 Some important formulations:
Piperazine citrate elixir I.P. 1966
Piperazine citrate ---- 18g
Chloroform spirit ---- 0.5 ml
Glycerin ---- 10 ml
Orange oil ---- 0.025ml
Syrup ---- 50 ml
Purified water to -- 100 ml

41

42
43

44
45

46
MIXTURE
 A mixture is a liquid preparation intended
for oral administration in which drugs may
be dissolved, suspended or dispersed in a suitable
vehicle. Generally several doses are contained in a
bottle.
Classification: Mixtures may be classified as follows:
 1. Simple mixtures
 2. Mixtures containing diffusible solids
 3. Mixtures containing indiffusible solids
 4. Mixture containing precipitate forming liquids

47

1. SIMPLE MIXTURE
 A simple mixture is one that contains only soluble ingredients.

Method of dispensing
(a) The solid substances are dissolved in 3/4th volume of the vehicle.
(b) The solution is examined against light for any foreign particle. If
foreign particles are present then the solution is passed through cotton
wool. Little vehicle is poured through the cotton wool to wash down any
drug present in the wool.
(c) Liquid ingredients, if any, are added and mixed.
(d) More vehicle is added to produce the final volume.
(e) The mixture is transferred to a bottle, capped tightly, polished and
labeled.

Container: Narrow mouthed, screw capped, colorless, plain bottle. 48

Label: The ink used in the label Black.
Special instructions: None
2. MIXTURE CONTAINING DIFFUSIBLE SOLIDS
 Diffusible solids are those, which are not
soluble in water, but on shaking they can be
mixed with it and remain evenly distributed
throughout the liquid for a sufficiently long
time. So dose transfer is uniform.
 However, on standing the insoluble solids
settle at the bottom. Whenever a dose is taken
the bottle should be shaken to redisperse the
solid.
 Examples of diffusible solids: Bismuth
carbonate, light kaolin, magnesium oxide,
magnesium carbonate, magnesium trisilicate
etc.
49

Method of dispensing
(a) All the solid ingredients are powdered in a mortar
and mixed thoroughly.
(b) Small amount of vehicle is added to the powder and
triturated to form a smooth paste.
(c) More volume of the vehicle is added.
(d) If foreign particles are present then the mixture is
strained though a muslin cloth.
(e) Liquid ingredient, if any, is added and the volume is
produced with the vehicle.
(f) The mixture is transferred to the bottle.
Container: Narrow mouthed, screw capped, colorless,
plain bottle.
Label: The ink used in the label Black.
Special instruction: SHAKE WELL BEFORE USE
50
 3. MIXTURE CONTAINING INDIFFUSIBLE
SOLIDS

 Indiffusible solids are those substances, which are not

soluble in water and they do not uniformly distribute
throughout the vehicle. Even after shaking they settle
quickly, therefore it becomes difficult to measure the dose
accurately. In this type of mixture a suspending agent is
used that increases the viscosity of the vehicle and thus
reduces the rate of settling of the particles.
 Examples of indiffusible solids: Chalk powder, acetyl
salicylic acid etc.
 Examples of suspending agents: Compound tragacanth
powder, Tragacanth mucilage, tragacanth powder.

51

 Method of dispensing
(a) Indiffusible, diffusible powders and calculated amount of
suspending agent are triturated in a mortar.

(b) Small mount of vehicle is added to the powder and

triturated to make a smooth paste.

(c) More amount of the vehicle is added. Strained through a

muslin cloth if any foreign particle is present.

(d) Liquid ingredient, if any, is added. Volume is made up with

the rest of the vehicle.
(e) The mixture is transferred to the bottle, capped, polished
and labeled.

Container: Narrow mouthed, screw capped, colorless, plain

bottle.
Label: The ink used in the label Black. 52
Special instruction(s): SHAKE WELL BEFORE USE
 4. MIXTURE CONTAINING PRECIPITATE
FORMING LIQUID
 Some liquid preparations contain resinous matter that is
precipitated on addition of water. This precipitates sticks to
the container and forms clots.
 To disperse this type of liquid first a protective colloid is
dispersed in vehicle and then the precipitate forming liquid is
added with constant stirring. The resinous particles are
coated with the protective colloid.

Examples of precipitate forming liquids:

 Compound benzoin tincture
 Benzoin Tincture
 Lobelia ethereal tincture
 Myrrh tincture
 Tolu Tincture
 Examples of suspending agents: Compound tragacanth 53
powder, Tragacanth mucilage

METHOD OF DISPENSING BY USING

COMPOUND TRAGACANTH POWDER
 (a) Any insoluble solid is powdered in a mortar
and mixed with compound tragacanth powder.
Small amount of the vehicle is added to form a
smooth paste. The volume is produced to 50% of
the final volume with the vehicle.
 (b) The precipitate forming liquid is taken in a
dry measuring cylinder and is added to the
suspension slowly, while the suspension is stirred
rapidly. The gum particles coat the resinous
particles and give a hydrophilic property to the
resin particles.
54
 METHOD OF DISPENSING BY USING
TRAGACANTH MUCILAGE
 (a) Mucilage is taken and added with equal
volume of vehicle in a beaker.
 (b) The precipitate forming liquid is measured
in a dry measuring cylinder and added into the
center of the mucilage with constant stirring.
 (c) If electrolyte is present, it is diluted with
vehicle and then mixed with the mucilage.
 (d) The mixture is strained, if required, and the
volume is produced with vehicle.
 (e) The mixture is transferred to the bottle,
capped, polished and labeled.
55

 (c) If any electrolytes are there it should be

added only after the resin particles are
completely coated with gum, otherwise heavy
clotting will take place.
 (d) Strained it necessary and volume is made up
with vehicle.
 (e) The mixture is transferred to the bottle,
capped, polished and labeled.

56
 Container: Narrow mouthed, screw capped,
colorless, plain bottle.
 Label: The ink used in the label Black.
Special instruction(s): SHAKE WELL BEFORE
USE

57

Liquids used for Oral Cavity

58
 59

Definition of Mouthwash

A medicated liquid used for

cleaning the oral cavity and
treating mucous membranes of
the mouth. may contribute to
surface softening and increased
wear of dental resins and
composite materials.
60
Types of Mouthwash
Fluoride mouthwashes contain sodium fluoride which
helps to strengthen the teeth as well as adding extra
protection against tooth decay.

cosmetic mouthwashes do not offer the same protection as

other types and are used more as a means of disguising bad
breath (halitosis).

Antiseptic mouthwashes contain chlorhexidine gluconate

- a chemical which stops the growth of bacteria and is
61
suitable for people with a mouth infection.

Natural mouthwashes are alcohol-free (and contain no

fluoride) and work in much the same way as conventional
mouthwashes.
They can also treat a mouth infection or injury.

Total care mouthwashes contain anti-bacterial ingredients

which help to reduce the build up of plaque and prevent gum
disease.

62
Advantages of Mouthwash:
can boost your oral health.

may prevent plaque from building up.

Rinses with fluoride can help prevent

cavities.

Fluoride protects against tooth decay

(cavities).

Mouthwash can help you target plaque.

63

Prevents dry mouth.

64
Disadvantages of
Mouthwash:
Some mouth rinses contain high levels of alcohol—ranging
from 18 to 26 percent. This may produce a burning sensation
in the cheeks, teeth, and gums.

65

Preparation and
Dispensing
of Mouthwashes

66
PREPARATION OF MOUTHWASHES
To prepare mouthwash
following ingredients are added:
Flavoring - such as eucalyptol
or menthol
Preservative- sodium benzoate.

Vehicle - Water

Sweeteners - sodium saccharine

and sucralose.
Colorants
67

Antiseptic agent - fluoride

 Detergent

PREPARATION OF SODIUM
CHLORIDE MOTHWASH
Sodiun Bicarbonate..10g
Sodium Chloride…….15g
Chloroform……….500ml
Pepprmintoil……….25ml
Water…….qty to prepare
1000ml

•Dissolve Na bicarbonate $ Nacl in 10

ml
•Add chloroform
68
& peppermint oil
•Makeup the volume
•Dispense the solution
PACKAGING & STORAGE
Containers:
fluted

plastic screw caps

Colorless bottles are

used unless protection from
light is necessary.
narrow mouthed

Storage:
 Store at room temperature

 Away 69from sunlight

 Keep out of reach of children

LABELING

•Product information
•Active ingredients
•Uses
•Warnings
•Direction
•Storage
•Inactive ingredients

70
DIRECTION TO USE
Before using a mouth rinse,
brush and floss teeth.
Measure the proper amount
of rinse
Dilute it before use
Thirty seconds is the
suggested rinsing time.
Do not rinse, eat, or smoke for
thirty minutes after using a
mouthwash.71

EXAMPLES OF MOUTH WASHES

Antisceptic: Listerene or
Phenolic mouthwash

 Analgesic: lidocaine
hydrochloride

Bactericidal (Cosmetic):
Fluoride mouthwash
72

 Anticavity: Floride rinse

GARGLES
73

DEFINITION :
Gargles are aqueous and hydro
alcoholic solution which is used
to treat or prevent throat
infection.

74
DIRECTIONS:
They are dispensed in concentrated
form with directions for dilution with
warm water.

They are brought into

intimate contact with
the mucous membrane
of the throat and allow to remain for
few moments
75

USES:
• Deodorant effect

• Anti-bacterial
•Astringen
t
• Mild anesthetic actions

76
STORAGE

 Store at room temperature

 Keep out of the reach of children.

Store away from direct sunlight,

heat and moisture.
77

LABELLING
 The label should include:
(1) the name of the pharmaceutical product;
(2) the name(s) of the active ingredients
(3) the amount of active ingredient in a suitable
dose-volume;
(4) the name and concentration of any
antimicrobial preservative and the name of any
other excipient;
(5) the batch (lot) number assigned by the
manufacturer;
(6) the expiry date and, when required, the date of
manufacture;
(7) any special storage conditions or handling
precautions that may be necessary;
(8) directions for use, warnings, and precautions
that may be necessary;
(9) the name and address of the manufacturer or
the person responsible for placing the product on 78
the market.
 Warnings
 Always read the label.
 Use only as directed.
 Avoid contact with the eyes.
 NOT TO BE SWALLOWED

Usage
 Dilute 1ml to 20ml with water gargle for 30 seconds,
repeat 3 to 4 hourly.

79

CONTAINER
 The containers should be
made of material that will not
adversely affect the quality of
the preparation
 containers should be made
from material that is
sufficiently transparent to
permit the visual inspection of
the contents
 preparation contains volatile
ingredients, it should be kept
80
in a tightly closed container
 PACKAGING
 Small flip top bottles

 Strong damp-proof, water-proof packing

81

Topic:
THROAT PAINT

82
 “Throat Paints are solutions
or dispersions of one or more
active ingredients intended for
application to the mucosa of
the throat or mouth.”

83

Throat paints are viscous due to

a high contact of glycerin, which
being sticky, adhere to the
affected site and prolong the
action of the medicaments.

84
1. Compound Iodine
Paint (Mandl‘s Paint) –
used for pharyngitis or
tonsillitis. Iodine throat
paint is designed to kill
germs. It can be used on
sore throats and ulcers
to ease them
2. Crystal Violet Paint –
used for thrush.
85

e.g. Mandl's Throat Paint

Formula:
 Potassium iodide 25g
Iodine 12.5g
Alcohol 90%v/v 40ml
Water 25ml
Peppermint oil 4ml
Glycerol up to 1000ml
86
(i) Potassium iodide is dissolved in
water.
(ii) Iodine is added in the concentrated
potassium iodide solutions to form KI3
(or higher iodides).
(iii) Peppermint oil is dissolved in alcohol
90%v/v and the alcoholic solution is
added to the iodine solution.
(iv) Volume is made up with glycerin. 87

ACTION: ANTISEPTIC

USES: Tonsillitis, Pharyngitis

ROLE OF INGREDIENT
 Potassium Iodide: To make soluble iodine in water

 Iodine: Antiseptic, Penetrate inn pores and have

germicidal effect, treat small abrasion and wounds in
Skin
 Alcohol: Preservative

 Water: Solvent

 Peppermint Oil: Flavoring agent

 Glycerin: Vehicle, Viscous, sticky, adhere to affected

88
site and prolong effect of medicament
A wide mouthed, fluted, light resistant,
screw-capped, glass-jar is used.
Dispense in amboured colored bottle
A wax card liner is used for screw caps
(because iodine attacks other
materials).
 Sinceglycerin is hygroscopic solvent, it
must be stored in tightly close container.
 A small quantity of Sodium Citrate or
acetate is added as preservative for longer
89

time

Apply with the help of soft brush or a

cotton swab.
Food and water before and after
application of throat paint, should be
avoided for 1 hour

90
 LABELING
 For local application
Store in a cool place.
Shake the bottle before use.
Not to be swallowed in large
amount.
Date: 01.01.03
 Advice to the patient:
Pharmacist should demonstrate the use
of throat brush to the patient. 91

LIQUIDS INSTILLED INTO BODY CAVITIES

92
Douches
Douche is an aqueous solution, which is directed against a
part or into a cavity of the body.
It functions as a cleansing or antiseptic agent.
Eye douches are used to remove foreign particles and
discharges from the eyes. It is directed gently at an oblique
angle and is allowed to run from the inner to the outer
corner of the eye.
Pharyngeal douches are used to prepare the interior of the
throat for an operation and to cleanse it in supportive
conditions.
Similarly, there are nasal and vaginal douches.
Douches most frequently dispensed in the form of a powder
with directions for dissolving in a specified quantity of
water.

Rx
Boric Acid Douche

Boric Acid 20gm

Purified water to 1000 ml
Enemas
 These preparations are rectal injections employed to:
evacuate the bowel (evacuation enemas),
influence the general system by absorption (retention
enemas) e.g. nutritive, sedative or stimulating properties
affect locally the site of disease (e.g. anthelmintic
property)
they may contain radiopaque substances for
roentgenographic examination of the lower bowel.
 Retention enemas are used in small quantities (about 30ml)
and are thus called retention microenema.
 Starch enema may be used either by itself or as a vehicle for
other forms of medication

Rx-1 Rx-2
Enema of Glycerin Soft Soap Enema
Glycerin 50 ml Soft Soap 50 gm
Purified 100 ml Purified 100 ml
water water
Nasal Solutions
Nasal solutions are usually aqueous solutions designed to be
administered to the nasal passages in drops or sprays.
 Ephedrine Sulfate or Naphaxoline Hydrochloride
Nasal Solution USP are administered for their local
effect to reduce nasal congestion
 Lypressin Nasal Solution USP for its systemic effect
for the treatment of diabetes insipidus

• The current route of administration of peptides and

proteins is limited to parental injection because of
inactivation within the GIT. As a result there is
considerable research on intranasal delivery of these
drugs such as insulin.

• Intranasal drug administration offers rapid

absorption to the systemic circulation. This route is
safe and acceptable alternative to the parental
administration

98
There is a direct route of transport from the olfactory region
to the central nervous system (CNS) without prior absorption
to the circulating blood. The olfactory receptor cells are
in contact with the nasal cavity and the CNS and they
provide a rout of entry to the brain that circumvents the
blood brain barrier

• Commercial nasal preparations include antibiotics,

antihistamines and drugs for asthma prophylaxis.

• Current studies indicate that nasal sprays are deposited in

the pharynx with the patient in an upright position.

Pharynx

• Drops spread more extensively than the spray and three

drops cover most of the walls of the nasal cavity, with the
patient in a supine position and head tilted back and turned
left and right.
 • Nasal decongestant solutions are employed in the
treatment of rhinitis of the common cold and for allergic
rhinitis (hay fever) and for sinusitis.

Sinuses are air-

containing cavities
in certain bones of
the skull

•Their frequent use or their use for prolonged periods may

lead to chronic edema of the nasal mucosa, i.e. rhinitis
medicainentosa, aggravating the symptom that they are
intended to relieve. Thus, they are best used for short
periods of time used for short periods of time (no longer than
3 to 5 days).

•Nasal solutions are prepared so that they are similar in

many respects to nasal secretions, so that normal ciliary
action is maintained thus aqueous nasal solutions usually
are isotonic and slightly buffered to maintain a pH of 5.5 to
6.5.
Sprays
Sprays are solutions of drugs in aqueous vehicles and are
applied to the mucous membrane of the nose and throat by
means of an atomizer nebulizer.
The spray device should produce relatively coarse droplets
if the action of the drug is to be restricted to the upper
respiratory tract. Fine droplets tend to penetrate further
into the respiratory tract than is desirable.

Many of the older sprays were prepared by dissolving

drug in light liquid petrolatum. This vehicle may retard the
normal ciliary action of the nasal mucosa and if drops of oil
enter the trachea, can cause lipoid pneumonia. Therefore
aqueous sprays, which are isotonic with nasal secretions and of
approximately the same pH are to be preferred. Such sprays
may contain antibiotics, antihistamines, vasoconstrictors,
alcohol, and suitable solubilizing and wetting agents.

They are used for the treatment of allergy and/or

vasodilatation (congestion) that occur with common cold.
Otic Solutions

The main classes of drugs used for topical

administration to the ear include local anesthetics,
e.g.: benzocaine; antibiotics e.g.; neomycin; and
anti-inflammatory agents, e.g.; cortisone.
These preparations include the main types of
solvents used, namely glycerin or water.
The viscous glycerin vehicle permits the drug to
remain in the ear for a long time.

Anhydrous glycerin, being hygroscopic,

tends to remove moisture from surrounding
tissues, thus reducing swelling.
Viscous liquids like glycerin or propylene
glycol either are used alone or in
combination with a surfactant to aid in the
removal of cerumen (ear wax).
In order to provide sufficient time for
aqueous preparations to act, it is necessary
for the patient to remain on his side for a
few minutes so the drops do not run out of
the ear.
106
108
 For a Middle Ear Infection:
While the person receiving Otic solution
lies on his/her side, the person giving the
drops should gently press the (TRAGUS
(4 times in a pumping motion. This will
allow the drops to pass through the hole
or tube in the eardrum and into the
middle ear.
For an Ear Canal Infection
While the person receiving the medication lies
on his/her side, the person giving the drops
should gently pull the outer ear upward and
backward. This will allow the ear drops to flow
down into the ear canal.

Ophthalmic Preparations

110
INTRODUCTION
The human eye is an amazing organ and the ability to
see is one of our most treasure possessions. Thus
the highest standards are necessary in the
compounding of ophthalmic preparation and the
greatest care is required in their used. It is
necessary that all ophthalmic preparation are
sterile and essentially free from foreign particles.

THE OPHTHALMIC PREPARATION MAY

BE CATEGORIZED AS FOLLOWS :
1. Eye drops including solution and suspension of active
medicament for instillation into the conjunctival sac.
2. Eye lotions for irrigation and cleaning the eye surface.
3. Eye ointment, creams, and gels containing active
ingredient(s) for application to the lid margins and/or
conjunctival sac.
4. Contect lens solution to facilitate the wearing and care
of contect lenses.
5. Parenteral product for intracorneal, intravitreous
or retrobulbar injection.
6. Solid dosage forms placed in the conjunctival sac
and designed to release active ingredient over a prolong
period.
MEDICAMENTS CONTAINED IN
OPHTHALMIC PRODUCTS INCLUDING :
 Anesthetics used topically in surgical procedure.
 Anti-infective such as antibacterial, antifungal, and
antiviral.
 Anti-inflammatory such as corticosteroid and
antihistamine.
 Antiglucoma agent to reduce intraocular pressure, such
as beta-blocker.
 Astringents such as zinc sulphate.

MEDICAMENTS CONTAINED IN OPHTHALMIC

PRODUCTS INCLUDING : ( CONT…)
 Diagnostic agents such as fluorescein which
highlight damage to the epithelial tissue.
 Miotics such as pilocarpine which constrict the pupil
and contract ciliary muscle increasing drainage
from the anterior chamber.
 Mydriatics and cycloplegics such as atropine which
dilate the pupil and paralysis the ciliary muscle and
thus facilitate the examination of the interior of the
eye.
 Eye Drops

FORMULATION OF THE EYE DROPS

 Active ingredient(s) to produce desired therapeutics
effect.
 Vehicle, usually aqueous but occasionally may be oil
e.g. tetracycline hydrochloride.
 Antimicrobial preservative.
 Adjuvant to adjust tonicity, viscosity or pH in order
to increase the comfort in use and to increase the
stability of the active ingredient(s).
 Suitable container for administration of eye drops
which maintains the preparation in a stable form and
protects from contamination during preparation,
storage and use.
ANTIMICROBIAL PRESERVATIVES
 Antimicrobial preservative to eliminate any
microbial contamination during use and thus
maintain sterility.
 It is essential for multiple dose of eye drops.

 Normal healthy eyes are quite efficient at

preventing penetration by microorganisms. Eye that
have damaged epithelia have their defenses
compromised and may be colonized by microorganism.
 The lack of vascularity of cornea and certain
internal structures of the eye make it very susceptible
and difficult to treat once infection has been establish.

ANTIMICROBIAL PRESERVATIVES ( CONT

…)
 No single substance is entirely satisfactory for use as a
preservative for ophthalmic solution. The system that
have been used.
 The eye drops supplied for use during intraocular
surgery should not contain a preservative because of the
risk of damage to the internal surface of the eye.
 Preservative suitable eye drops such as
Benzalkonium chloride 0.1% w/v, chlorhexidine
acetate 0.01 % w/v, chlorbutol 0.5 % w/v,
phenylmercuric salts 0.001-0.04 % w/v, thiomersal 0.005-
0.01 % w/v.
TONICITY
 may possible eye drops are made isotonic with
lachrymal fluid ( approximately equivalent to 0.9 %
w/v sodium chloride solution ).
 The eye will tolerate small volumes of eye drops
having tonicities in the range equivalent 0.7 – 1.5 % w/v
sodium chloride.
 The tonicity of hypotonic eye drops by addition of the
tonicity of the lachrymal fluid.

VISCOSITY ENHANCERS
 There is general assumption
that increase the viscosity of an
eye drop increase the
residence time of the drop in the
eye and results in increase
penetration and therapeutic
action of the drug.
 Viscosity enhancers including
polyvinyl alcohol 1.4 % w/v &
methylcellulose derivative
such as hypromellose ―
hydroxypropyl derivative of
methylcellulose‖ 0.5 – 2 % w/v.
PH ADJUSTMENT
 the best compromise is required after considering the
following factors:
 the pH offering best stability during preparation and storage.
 The pH offering the best therapeutic activity.
 the comfort of the patient.

PH ADJUSTMENT ( CONT …)
 Most active ingredient are salts of weak bases and
are most stable at an acid pH but most active at a
slightly alkaline pH.
 The lachrymal fluid has a pH of 7.2 – 7.4 and
also possesses considerable buffering capacity. Thus a 50
mcl eye drop which is weakly buffered will be
rapidly neutralized by lachrymal fluid. Where possible
very acidic solution, such as adrenalin acid tartrate
or pilocarpine hydrochloride are buffered to reduce
stinging instillation.
 Suitable buffers for eye drops including Borate
buffer, Phosphate buffer, Citrate buffer.
ANTIOXIDANTS
 Reducing agent are preferentially oxidizing and are
added to eye drops in order to protect the active
ingredient from oxidation.
 Active ingredient requiring protection including
adrenalin, sulphacetamide, phenylephedrine…etc.

CHELATING AGENT
 Traces of heavy metals can catalyse breakdown of active
ingredient by oxidation and other mechanism.
Therefore chelating agent such as disodium edetate
may be including to chelating the metal ions and thus
enhance stability.
 disodium edetate is a very useful adjuvant to
ophthalmic preparations at concentration of up to 0.1
% w/v to enhance antimicrobial activity & chemical
stability.
CONTAINER OF EYE DROPS
 Container should be regarded as part of the
total formulation.
 They should protect the eye drops from
microbial contamination, moisture and air.
 Container materials should not be shed or
leached into solution neither should any of the eye drop
formulation be sorbed by the container.
 If the product is to sterilized in the final container all
parts of the container must withstand the sterilization
method.
 Container may be made of glass or plastic and may
be single or multiple dose. The latter should not contain
more than 10 ml.

EYE LOTIONS

126
 EYE LOTIONS ARE STERILE AQUEOUS
SOLUTIONS INTENDED FOR USE IN
WASHING OR BATHING THE EYE OR FOR
IMPREGNATING EYE DRESSINGS.

Eye lotions may contain excipients, for example

to adjust the tonicity or the viscosity of the
preparation or to adjust or stabilise the pH.

These substances do not adversely affect the

intended action or, at the concentrations used,
cause undue local irritation.

EYE LOTIONS SUPPLIED IN MULTI-DOSE

CONTAINERS CONTAIN A SUITABLE
ANTIMICROBIAL PRESERVATIVE IN
APPROPRIATE CONCENTRATION EXCEPT
WHEN THE PREPARATION ITSELF HAS
ADEQUATE ANTIMICROBIAL PROPERTIES.

The antimicrobial preservative chosen is compatible with

the other ingredients of the preparation and remains
effective throughout the period of time during which the
eye lotions are in use.
If eye lotions are prescribed without an antimicrobial
preservative, they are supplied in single-dose
containers.
Eye lotions intended for use in surgical procedures or in
first-aid treatment do not contain an
antimicrobial preservative and are supplied in
single-dose containers.
Eye lotions examined under suitable
conditions of visibility, are practically
clear and practically free from particles.
The containers for multidose preparations do not
contain more than 200 ml of eye lotion,
unless otherwise justified and authorised.

CHARACTERISTICS OF AN EYE LOTION :

 Sterileand usually containing no

preservative

 Isotonic with lachrymal fluid

 Neutral pH

 Largevolume but not greater than

200 mL

 Non-irritant to ocular tissue

LABELLING

1. Title identifying the product and

concentration of contents
2. ‗Sterile until opened‘
3. ‗Not to be taken‘
4. ‗Use once and discard remaining
solution‘
5. Expiry date

PRESERVED EYE LOTION WOULD

NEED THE ADDITIONAL LABELLING:

„Avoid contamination of contents

during use‟

„Discard remaining solutions not

more than 4 weeks after first
opening‟

The lotions should be supplied in coloured fluted

bottles and sealed to exclude microorganisms.
EYE OINTMENTS, CREAMS OR GELS

133

SEMI-SOLID EYE PREPARATIONS ARE STERILE

OINTMENTS, CREAMS OR GELS INTENDED FOR
APPLICATION TO THE CONJUNCTIVA.
THEY CONTAIN ONE OR MORE ACTIVE SUBSTANCES
DISSOLVED OR DISPERSED IN A SUITABLE BASIS.
THEY HAVE A HOMOGENEOUS APPEARANCE.

Semi-solid eye preparations comply with the

requirements of the monograph on Semi-solid
preparations for cutaneous application.
The basis is non-irritant to the conjunctiva.
SEMI-SOLID EYE PREPARATIONS ARE PACKED IN
SMALL, STERILISED COLLAPSIBLE TUBES FITTED
OR PROVIDED WITH A CANNULA AND HAVING A
CONTENT OF NOT MORE THAN 5 G OF THE
PREPARATION.

The tubes must be well-closed to prevent microbial

contamination.
Semi-solid eye preparations may also be packed in
suitably designed single-dose containers.
The containers, or the nozzles of tubes, are of such
a shape as to facilitate administration without
contamination.
Tubes are tamper-proof.

Ointments have the disadvantage of temporarily

interfering with vision, but have the advantage
over liquids of providing greater total drug
bioavailability.

However, ointments take a longer time to reach peak

absorption.
 REQUIREMENTS TO THE SEMI-
SOLID EYE DRUGS
1. Sterility
2. The absence of irritating
3. Stability
4. A good distribution of MS
5. Softness consistency
6. Good contact with eye
7. Rapid formation of thinnest film on the
eyeball
8. Lack of adhesion for ever
9. There should be soft, and at 15-50 º C
have a stable viscosity.

TECHNOLOGY OF THE EYE OINTMENTS

1. Preparing of the ointments base

2. Production of the ointments base
3. Filtering of the ointments base
4. Introducing MS in the ointments base
5. Homogeny of the ointment
6. Packaging, labeling.
 Eye ointments are normally prepared using
aseptic techniques to incorporate the finely
powdered active ingredient or a sterilized
concentrated solution of the medicament into
the sterile eye ointment basis.

Immediately after preparation the eye ointment

is filled into the sterile containers which are
then sealed so as to exclude microorganisms.

The screw cap should be covered with a readily

breakable seal.

All apparatus used in the preparation of eye

ointments must be scrupulously clean and sterile.

Certain commercial eye ointments may be sterilized

in their final containers using ionising radiation.
 PREPARATION OF EYE OINTMENT
BASIS
The paraffins and the wool fat are heated together and
filtered, while molten, through a coarse filter paper in
a heated funnel into a container which can withstand
dry heat sterilization temperatures.

The container is closed to exclude microorganisms and

together with contents is maintained at 160°C for 2
hours.

CONTAINERS FOR EYE OINTMENTS

Eye ointments should be supplied in small sterilized
collapsible tubes made of metal or in a suitable plastic.

The tube should not contain more than 5g of preparation

and must be fitted or provided with a nozzle of a
suitable shape to facilitate application to the eye and
surrounds without allowing contamination of the contents.

The tubes must be suitably sealed to prevent microbial

contamination.

Eye ointment may also be packed in suitably designed

single-dose containers.
LABELLING
 The names and percentages of the active ingredients.

 The date after which the eye ointment is not

intended to be used.

 The conditions under which the eye ointment should be

stored – normally at a temperature not exceeding 25°C..

 The name and concentration of any antimicrobial

preservative or other substance added to the
preparation

 A statement to the effect that the contents are

sterile providing the container has not been
opened.

OPHTHALMIC INSERTS

144
OPHTHALMIC INSERTS – IS STERILE DRUGS ARE
INTENDED FOR INSERTING IN THE CONJUNCTIVE SAC.
THEY CONSIST OF MATRIX, WHICH INCLUDES MS IN
THE MEMBRANE CONTROLLING RATE OF THE
MEDICINES SUBSTANCES RELEASE.

Ophthalmic inserts are solid or semi-solid preparations

of suitable size and shape, designed to be inserted in
the conjunctival sac, to produce an ocular effect.

ADVANTAGES OF OPHTHALMIC
INSERTS:

1. Accuracy of dosing.
2. Convenience of using.
3. Prolonged action.
4. Absence of the allergic reaction.
5. Shorter time of the coarse treatment in
2-3 time.
CLASSIFICATION OF THE EYE INSERTS:
 Soluble
 Insoluble

 Soluble in the biological liquid – is matrices

with homogenous dispersible MS, which is
included (or not) in the hydrophobic layer.
Layer isn‟t penetrated for active substances.

SOLUBLE OPHTHALMIC INSERTS:

1. Natural polymers (collagen) are base of the

inserts.
2. Artificial (man-made) polymers (methylcellulose)
are base of the inserts.

Disadvantages:
- High rate of penetration of tear fluid.

- Blurred vision.
CLASSIFICATION OF INSOLUBLE
OPHTHALMIC INSERTS:

a) Diffuse system, consisting of a central reservoir with

drugs in it.

b) Osmotic system, consisting of the central part

surrounded by the peripheral part.
The central part has as simple reservoir and two different
departments.
In the reservoir there is MS and auxiliary substances to
create osmotic pressure.

c) Hydrophilic contact lenses is a coherent system that

consists of a polymer that allows you to keep aqueous
solutions of the MS or solid components.

CLASSIFICATION OF THE
CONTACT LENSES

1. Rigid

2. Semi-rigid

3. Elastomeric

4. Soft hydrophilic

5. Biopolymeric
CHARACTERIZATION OF THE CONTACT
LENSES:
Advantage of the Disadvantage
lenses – they are  Permanent contact
able to correct with hands.
refractive defects of
 Required frequent
vision and improves washing, which
visual acuity.
causes the risk of
contamination and
loss of drugs
 High price.

Introduction
 Emulsions

1) DEFINITION.
2) TYPES OF EMULSIONS.
3) ADVANTAGES/ DISADVANTAGES.
4) TEST OF IDENTIFICATIONS.
5) EMULSIFYING AGENTS.
6) TYPES OF EMULSIFYING AGENTS.
7) THEORIES OF EMULSIFICATION.
8) PREPARATION OF EMULSIONS.
9) STABILITY OF EMULSIONS.

DEFINITION
 An Emulsion is a mixture of two or more liquids
that are normally Immiscible.

Oil
Oil Agitation Oil

Water Water
Water

Separate rapidly into two

clear defined layers

OR
 Emulsion, is a mixture of two or more liquids in
which one is present as droplets, of microscopic or
ultramicroscopic size, distributed throughout the
other.
INTERNAL PHASE OR EXTERNAL PHASE IN
EMULSIONS:

 The dispersed liquid is known as the Internal or

Discontinuous phase.

 whereas the dispersion medium is known as

the External or Continuous phase.
 TYPES OF EMULSIONS

Based on dispersed phase:

 Oil in Water (O/W): Oil droplets dispersed in
water.
 Water in Oil (W/O): Water droplets dispersed in
oil.
 Water in Oil in water (W/O/W): Water in Oil
emulsion dispersed in water – multiple emulsion.
Based on size of liquid droplets:
 0.2 – 50 mm Macroemulsions
 0.01 – 0.2 mm Microemulsions

ADVANTAGES OF EMULSIONS:
 Mask the unpleasant taste O/W is convenient means of
oral administration of water-insoluble liquids.

 Oil-soluble drugs can be given parentrally in form of oil-in

water emulsion. (e.g Taxol).

 Emulsion can be used for external application in cosmetic

and therapeutic Application because of Better and faster
absorption.

 Sustained release medication.

 Nutritional supplement.
 Inert and chemically non-reactive.
 Reasonably odorless and cost Effective.
 Radiopague agents for diagnostic purposes.

 Intravenous Nutrition (maintenanceof debilitated

patients)- Intralipid, Nutralipid).

 Fluorocarbon Emulsions- fluorocarbons have

high capacities for dissolving gases like O2 and
CO2 and serve as blood substitutes for a short
period of time.

DISADVANTAGES OF EMULSIONS:

 Emulsions are thermodynamically unstable and

have short shelf-life.

 Improper formulation of emulsions leads to

creaming and cracking of emulsion.

 Improper selection of emulsifying agent leads to

phase inversion and some times it may also lead
to cracking.
IDENTIFICATION TEST FOR EMULSIONS:
By using Naked eye, it is very difficult to
differentiate between o/w or w/o emulsions. Thus,
the following methods have been used to identify
the type of emulsions.

1) Dye Test
2) Dilution Test
3) Electrical conductivity Test
4) Fluorescence Test.
5) Cobalt Chloride Test.

1) DYE TEST:
 Water-soluble dye will dissolve in the aqueous
phase.
 Oil-soluble dye will dissolve in the oil phase.
Microscopic View

Oil-soluble dye (e.g. Scarlet) Water-soluble dye (e.g. Amaranth dye)

W/O O/W O/W W/O

2) DILUTION TEST:
Based on the solubility of external phase of
emulsion.
 O/W emulsion can be diluted with water.

 W/O emulsion can be diluted with oil.

Few drops
of water Water distribute
uniformly O/W emulsion

Few drops Water separate

of emulsion out as layer W/O emulsion

3) ELECTRICAL CONDUCTIVITY TEST:

 As we know water is good conductor of electricity
whereas oil is non-conductor. Therefore,
continuous phase of water runs electricity more
than continuous phase of oil.

Bulb
 Bulb glows with O/W
 Bulb doesn’t glow with W/O

Electrode
Emulsion
3) FLUORESCENCE TEST:
 Oils give fluorescence under UV light, while
water doesn‘t.

 Therefore, O/W emulsion shows spotty pattern

when observed under UV.

 while W/O emulsion fluoresces.

4) COBALT CHLORIDE TEST:

 Principle:
 Cobalt Chloride solution is used for identification
of Emulsion. It is water soluble so it changes
colour when encountered by O/W emulsion.
Procedure:
Filter paper is Dipped in Emulsion.
Filter paper changes its color from blue to Pink

Result:
Emulsion is O/W otherwise not.
 EMULSIFYING AGENT:
 Definition: Emulsions are stabilized by adding an
emulsifying agent. These agents have both a
hydrophilic and a Lipophilic part in their chemical
structure. All emulsifying agents get adsorbed onto
the Oil : water interface to provide a protective barrier
around the dispersed droplets. In addition to this
protective barrier, emulsifiers stabilize the emulsion
by reducing the interfacial tension of the system.

CLASSIFICATION OF EMULSIFYING
AGENTS:
 Emulsifying agents can be classified according to:
1) chemical structure:
 Synthetic Emulsifying Agents
 Natural Emulsifying Agents
 Finely Dispersed Solids
 Auxilary Agents

2) Mechanism of action:
 Monomolecular

 Multi-molecular

 Solid particle films.

SYNTHETIC EMULSIFYING AGENTS
1) Anionic: (pH > 8)
 Sodium stearate
 Potassium laurate
 Sodium dodecyl sulfate
 Sodium sulfosuccinate.
 Sodium or potassium oleate
 Triethanolamine stearate
 sodium lauryl sulfate.

2) Cationic: (pH 3-7)

 Benzalkonium chloride,
 Benzethonium chloride
 Quaternary ammonium salts.

3) NON IONIC (PH 3-10)

 Polyglycol,
 Fatty acid esters,
 Lecithin.
 Sorbitan esters (Spans).
 Polyoxyethylene derivatives of sorbitan esters
(Tweens),
 Glyceryl esters.

* * * Cationic and Anionic surfactants are generally

limited to use in topical, o/w emulsions * * *
 NATURAL EMULSIFYING AGENTS
Derived from Plants and Animals:
Vegetable derivatives:
 Acacia

 Tragacanth

 Agar

 Pectin

 Carrageenan

 Lecithin

Animal derivatives:
 Gelatin

 Lanolin

 Cholesterol

FINELY DIVIDED OR FINELY

DISPERSED SOLID PARTICLE EMULSIFIERS
 These agents form a particulate layer around
dispersed particles. Most will swell in the
dispersion medium to increase viscosity and
reduce the interaction between dispersed
droplets. Most commonly they support the
formation of o/w emulsions, but some may
support w/o emulsions. For Instance,,
 Bentonite
 Veegum,
 Hectorite,
 Magnesium Hydroxide,
 Aluminum Hydroxide
 Magnesium Tri silicate.
 AUXILIARY EMULSIFYING AGENTS

 A variety of fatty acids (e.g., stearic acid), fatty

alcohols (e.g., stearyl or cetyl alcohol), and fatty
esters (e.g., glyceryl monostearate) serve to
stabilize emulsions through their ability to
thicken the emulsion..
 A system was developed to assist in making
systemic decisions about the amounts and types
of surfactants needed in stable products. The
system is called the HLB (hydrophile-lipophile
balance) system and has an arbitrary scale of 1 -
18. HLB numbers are experimentally determined
for the different emulsifiers. .

 Low HLB Indicates ?

 Low number of hydrophilic groups on the
Molecule thus imparting Lipophilic character:

 Spans have low HLB numbers, Because of their

oil soluble character, Spans will cause the oil
phase to predominate and form an w/o emulsion.
 High HLB indicates ?
 Emulsifier has a large number of hydrophilic
groups on the molecule thus imparting
hydrophilic Character.
 Tweens have higher HLB numbers, Because of
their water soluble character, Tweens will cause
the water phase to predominate and form an o/w
emulsion.
 HLB VALUE & APPLICATION

 1~3 Anti-foaming agent.

 3~6 W/o emulsifying agents.
 7~9 Wetting agents.
 8 ~ 18 O/w emulsifying agents.
 13 ~15 Detergents.
 15 ~18 Solubilizing Agents.

HOW TO CALCULATE HLB ????

 Combinations of emulsifiers can produce more
stable emulsions than using a single emulsifier
with the same HLB number. The HLB value of a
combination of emulsifiers can be calculated as
follows:
NUMERICAL 1:
 What is the HLB value of a surfactant system
composed of 20 g Span 20 (HLB = 8.6) and 5 g
Tween 21 (HLB = 13.3)?

Water

Oil
CLASSIFICATION OF EMULSIONS BASED ON
MECHANISM OF ACTION:

1) Monomolecular film: To reduce the interfacial

tension Oil droplets are surrounded by a coherent
monolayer of the surfactant which prevents coalescence.
If the emulsifier is ionized, the presence of strong charge
may lead to repulsion in droplets and hence increasing
stability. Adsorbed at oil/water interface to form

2) Multimolecular film or Hydrophillic Colloids

3) Finely divided solid particles: They are adsorbed

at the interface between two immiscible liquid
phases to form Particulate film.
THEORIES OF EMULSIFICATION:
Many theories have been advanced to account for
the way or means by which the emulsion is
stabilized by the emulsifier. At the present time
no theory has been postulated that seems to
apply universally to all emulsions.

1) Electric Double Layer Theory.

2) Phase Volume Theory.
3) Hydration Theory of Emulsions
4) Oriented wedge theory.
5) Adsorbed Film and Interfacial tension Theory

1) ELECTRIC DOUBLE LAYER THEORY:

The oil globules in a pure oil and pure water
emulsion carry a negative charge. The water
ionizes so that both hydrogen and hydroxyl ions
are present. The negative charge on the oil may
come from adsorption of the OH ions. These
adsorbed hydroxyl ions form a layer around the
oil globules. A second layer of oppositely charged
ions forms a layer in the liquid outside the layer
of negative ions. These two layers of oppositely
charged ions are known as the Helmholtz double
layer. They are not confined to emulsions but
accompany all boundary phenomena. The electric
charge is a factor in all emulsions, even those
stabilized with emulsifying agents
2) PHASE VOLUME THEORY:
If spheres of the same diameter are packed as closely as
possible, one sphere will touch 12 others and the
volume the spheres occupy is about 74 per cent of the
total volume. Thus if the spheres or drops of the
dispersed phase remain rigid it is possible to disperse
74 parts of the dispersed phase in the continuous
phase; but if the dispersed phase is increased to more
than 74 parts of the total volume, a reversal of the
emulsion will occur. However, the dispersed phase
does not remain rigid in shape but the drops flatten
out where they come in contact with each other, nor
are all the dispersed particles the same, so that it is
possible for the dispersed phase to consist of from 1 to
99 per cent of the emulsion.

3) HYDRATION THEORY OF EMULSIONS:

 Fischer and Hooker state that hydrated colloids
make the best emulsifiers. Fischer states the
emulsifying agent, by which a permanent
emulsion is obtained, invariably "proves to be a
hydrophilic colloid when water and oil emulsions
are concerned (a lyophilic colloid of some sort
when other than aqueous mixtures are under
consideration). Put another way, oil cannot
permanently be beaten into water, but only into a
colloid hydrate."
 Fischer and Hooker have found albumin, casein,
and gelatin to be good emulsifying agents.
4) ORIENTED WEDGE THEORY:
 This theory deals with formation of monomolecular layers of
emulsifying agent curved around a droplet of the internal
phase of the emulsion.
Example:
 In a system containing 2 immiscible liquids, emulsifying
agent would be preferentially soluble in one of the phases and
would be embedded in that phase.

 Hence an emulsifying agent having a greater hydrophilic

character will promote o/w emulsion and vice-versa.

 Sodium oleate is dispersed in water and not oil. It forms a

film which is wetted by water than by oil. This leads the film
to curve so that it encloses globules of oil in water.

 Sodium Oleate Zinc Oleate

5) ADSORBED FILM AND INTERFACIAL TENSION

THEORY:
 Lowering interfacial tension is one way to decrease
the free surface energy associated with the formation
of droplets. Assuming the droplets are spherical,

 ΔF= 6 γV
D
 V= volume of the dispersed phase in ml, d is the mean
diameter of the particles.
 γ = interfacial tension

 It is desirable that:
 The surface tension be reduced below 10dynes/cm by
the emulsifier and Be absorbed quickly.
6) SURFACE TENSION THEORY:

 A drop of liquid forms a spherical shape which

gives it the smallest surface area per unit volume
 When 2 drops come together to form a bigger
drop- gives lesser surface area. Also called
surface tension at air-liquid interface
 Surface Tension- Force that has to be applied
parallel to the surface of liquid to counterbalance
exactly the internal inward forces that tend to
pull the molecule together.
 When there are two immiscible liquids-it is called
interfacial tension.

METHODS OF PREPARATION OF EMULSIONS:

 Commercially, emulsions are prepared in large

volume mixing tanks and refined and stabilized
by passage through a colloid mill or homogenizer.
Extemporaneous production is more concerned
with small scale methods.

 1) Dry Gum Methods

 2) Wet Gum Methods
 3) Bottle Method
 4) Beaker Method.
 5) In situ Soap Method.
DRY GUM METHOD FOR PREPARATION OF
EMULSIONS:
 Dry gum method is used to prepare the initial or
primary emulsion from oil, water, and a
hydrocolloid or "gum" type emulsifier.

Dry Gum Methodology

(4 parts oil, 2 parts water, and 1 part Emulsifier).

 Procedure: Take mortar, 1 part gum is levigated

with the 4 parts oil until the powder is
thoroughly wetted; then the 2 parts water are
added all at once, and the mixture is vigorously
triturated until the primary emulsion formed is
creamy white and produces a "crackling" sound
as it is triturated.

 Active ingredients, preservatives, color, flavors

are added as a solution to the primary emulsion.

 When all agents have been incorporated, the

emulsion should be transferred to a calibrated
vessel, brought to final volume with water.
 WET GUM METHOD
Methodology
(Oil 4 parts + Water 2 parts + Emulsifier 1 parts)
Procedure: In this method, the proportions of oil,
water, and emulsifier are the same (4:2:1), but
the order and techniques of mixing are different.
The 1 part gum is triturated with 2 parts water
to form a mucilage; then the 4 parts oil is added
slowly, in portions, while triturating. After all the
oil is added, the mixture is triturated for several
minutes to form the primary emulsion. Then
other ingredients may be added as in the
continental method. Generally speaking, the
English method is more difficult to perform
successfully, especially with more viscous oils,
but may result in a more stable emulsion.
 BOTTLE METHOD
 This method may be used to prepare emulsions of
volatile oils, Oleaginous substances of very low
viscosities.

 This method is a variation of the dry gum method.

 One part powdered acacia (or other gum) is placed in

a dry bottle and four parts oil are added. The bottle is
capped and thoroughly shaken. To this, the required
volume of water is added all at once, and the mixture
is shaken thoroughly until the primary emulsion
forms.
 Reference:
http://pharmlabs.unc.edu/labs/emulsions/beaker.htm

BEAKER METHOD
 The most appropriate method.
 Dividing components into water soluble and oil
soluble components.
 All oil soluble components are dissolved in the oily
phase in one beaker and all water soluble
components are dissolved in the water in a separate
beaker.
 Oleaginous components are melted and both phases
are heated to approximately 70°C over a water bath.
The internal phase is then added to the external
phase with stirring until the product reaches room
temperature.
IN SITU SOAP METHOD:
 Two types of Soaps developed by this Methods:
1) Calcium Soaps
2 ) Soft Soaps
1) Calcium Soaps: W/O type Emulsions. E.g. Oleic
acid + Lime water. Prepared by simple mixing
of equal volumes of Oil and Lime water.

 Emulsifying agent used is Calcium salt of free

fatty acids. E.g. Olive Oil + Oleic acid (FAA) =
calcium Oleate.
Advantage: O/W is external Phase used frequently
on dry skin and sun burned skin.

CALAMINE LINIMENTPREPARATION:

 Calamine…………….
 Zinc Oxide................ 80g

 Olive Oil……………..

 Calcium Hydro Oxide sol. 1000ml

STABILITY ISSUES:
1. Emulsions are, by nature, physically unstable; that
is, they tend to separate into two distinct phases or
layers over time.
2. Creaming occurs when dispersed oil droplets
merge and rise to the top of an o/w emulsion or
settle to the bottom in w/o emulsions. In both cases,
the emulsion can be easily redispersed by shaking.
3. Coalescence (breaking or cracking) is the
complete and irreversible separation and fusion of
the dispersed phase.
4. Phase inversion or a change from w/o to o/w (or
vice versa) may occur. This is considered a type of
instability by some.

 Addition of Electrolyte: Addition of Cacl2 into

O/W emulsion formed by sodium stearate will be
inverted into W/O.
PHARMACEUTICAL
SUSPENSIONS

SUSPENSIONS

CONTENTS
Definition.

Classification.
SUSPENSIONS

Advantages & disadvantages.

Applications.
Theoretic consideration of suspensions.
•Sedimentation
•Brownian movement
•Electrokinetic properties
 Formulation of suspensions

Packing of suspensions

SUSPENSIONS
Storage requirement & labelling

Evaluation of suspension

Dissolution study of suspensions

Innovation of suspensions

201

2
0 SUSPENSIONS
2
 DISPERSE SYSTEM

 The term "Disperse System" refers to a system in which one

substance (The Dispersed Phase) is distributed, in discrete
units, throughout a second substance (the continuous Phase ).

 Each phase can exist in solid, liquid, or gaseous state .

 Suspensions are heterogenous system consisting of 2 phases.

2
0 SUSPENSIONS
3

A solid in liquid dispersion in which the particles are

of colloidal size.

DISPERSE SYSTEM
SUSPENSIONS

DISPERSED MEDIUM DISPERSED PHASE

oAqueous oily liquid oInsoluble solid

204
 Definition

 A Pharmaceutical suspension is a coarse dispersion in which internal

phase (therapeutically active ingredient)is dispersed uniformly
throughout the external phase.

2
0 SUSPENSIONS
5

 The internal phase consisting of insoluble solid particles

having a range of size(0.5 to 5 microns) which is
maintained uniformly through out the suspending vehicle
with aid of single or combination of suspending agent.

 The external phase (suspending medium) is generally

aqueous in some instance, may be an organic or oily
liquid for non oral use.

2
0 SUSPENSIONS
6
The reasons for the formulation of a pharmaceutical
suspension:

-- when the drug is insoluble in the delivery vehicle.

–To mask the bitter taste of the drug.

–To increase drug stability.

–To achieve controlled/sustained drug release.

2
0 SUSPENSIONS
7

SOME MARKETED
SOME PHARMACEUTICAL SUSPENSIONS
SUSPENSIONS

 1. Antacid oral suspensions

 2. Antibacterial oral suspension

 3. Dry powders for oral suspension (antibiotic)

 4. Analgesic oral suspension

 5. Anthelmentic oral suspension

 6. Anticonvulsant oral suspension

 7. Antifungal oral suspension

2
0 SUSPENSIONS
8
 Classification
Based On General Classes
 Oral suspension
eg: Paracetamol suspension
antacids, Tetracycline HCl.

 Externally applied suspension

eg :Calamine lotion.

 Parenteral suspension
eg: Procaine penicillin G
Insulin Zinc Suspension 209

SUSPENSIONS

Based on Proportion of Solid Particles

 Dilute suspension (2 to10%w/v solid)

Eg: cortisone acetate, predinisolone acetate

SUSPENSIONS

 Concentrated suspension (50%w/v solid)

Eg: zinc oxide suspension

210
Based on Electrokinetic Nature of Solid Particles

 Flocculated suspension

 Deflocculated suspension

2
1 SUSPENSIONS
1

Based on Size of Solid Particles

SUSPENSIONS

Colloidal suspensions (< 1 micron)

-Suspensions having particle sizes of suspended solid less than

about 1micron in size are called as colloidal suspensions.

212
 Coarse suspensions (>1 micron)
Suspensions having particle sizes of greater than about
1micron in diameter are called as coarse suspensions.

SUSPENSIONS
Coarse dispersion
Barium sulphate

Nano suspensions (10 ng)

 Suspensions are the biphasic colloidal dispersions of

nanosized drug particles stabilized by surfactants.
Size of the drug particles is less than 1mm.
213

Advantages And Disadvantages

Advantages
.Suspension can improve chemical stability of certain drug.
E.g. Procaine penicillin G.

Drug in suspension exhibits higher rate of bioavailability than other

dosage forms.

Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

Duration and onset of action can be controlled.

E.g. Protamine Zinc-Insulin suspension.

Suspension can mask the unpleasant/ bitter taste of drug.

E.g. Chloramphenicol
2
1 SUSPENSIONS
4
 Disadvantages

 Physical stability , sedimentation and compaction can causes

problems.

 It is bulky sufficient care must be taken during handling and

transport.

 Uniform and accurate dose can not be achieved unless

suspension are packed in unit dosage form.

2
1 SUSPENSIONS
5

Applications

 Suspension is usually applicable for drug which is insoluble

(or ) poorly soluble.
E.g. Prednisolone suspension
SUSPENSIONS

 To prevent degradation of drug or to improve stability of

drug.
E.g. Oxy tetracycline suspension

 To mask the taste of bitter of unpleasant drug.

E.g. Chloramphenicol palmitate suspension

 Suspension of drug can be formulated for topical application

216
e.g. Calamine lotion
 Suspension can be formulated for parentral application in order to
control rate of drug absorption. E.g. penicillin procaine

SUSPENSIONS
 Vaccines as a immunizing agent are often formulated as suspension.
E.g. Cholera vaccine

 X-ray contrast agent are also formulated as suspension .

eg: Barium sulphate for examination of alimentary tract.

217

Features Desired In Pharmaceutical Suspensions

 The suspended particles should not settle rapidly and sediment
produced, must be easily re-suspended by the use of moderate
amount of shaking.

 It should be easy to pour yet not watery and no grittiness.

 It should have pleasing odour , colour and palatability.

 Good syringeability.

 It should be physically,chemically and microbiologically stable.

 Parenteral /Ophthalmic suspension should be sterilizable.

2
1 SUSPENSIONS
8
THEORITIC CONSIDERATION OF SUSPENSIONS

A knowledge of the theoretic considerations pertaining to

suspension s technology ultimately help formulator to select
ingredients that are

Appropriate for suspension preparation

That available for milling

Mixing equipment

2
1 SUSPENSIONS
9

Some theoretic considerations are :

Particle size control.

Wetting

Sedimentation

 Brownian movement

Electokinetic

Aggregation
2
2 SUSPENSIONS
0
Particle size control:
Particle size of any suspension is critical and must
-
be reduced within the range .
-Too large or too small particles should be avoided.
Larger particles will:
 settle faster at the bottom of the container
 particles > 5 um impart a gritty texture to the product
and also cause irritation if injected or instilled to the eye
 particles > 25 um may block the needle

-Too fine particles will easily form hard cake at the bottom
of the container.

2
2 SUSPENSIONS
1

Wetting of the particles

 Hydrophilic materials (talc, ZnO, Mg2CO3) are easily
wetted by water while hydrophobic materials (sulphur , charcoal) are
not due to the layer of adsorbed air on the surface.

 Thus, the particles, even high density, float on the surface of the liquid
until the layer of air is displaced completely.

 The use of wetting agent allows removing this air from

the surface and to easy penetration of the vehicle into the pores.

 However hydrophobic materials are easily wetted by

non-polar liquids.

2
2 SUSPENSIONS
2
 THEORY OF SEDIMENTATION

SEDIMENTATION:

Sedimentation means settling of particle (or) floccules occur

under gravitational force in liquid dosage form.

2
2 SUSPENSIONS
3

2.1.

Velocity of sedimentation expressed by Stoke’s equation

Where,
d = Diameterof particle
SUSPENSIONS

r = radius of particle

vsed.= sedimentation velocity in cm / sec

ρ s= density of disperse phase

ρ o= density of disperse media

g = acceleration due to gravity

η o = viscosity of disperse medium in poise
224
Limitation Of Stoke’s Equation .

Stoke's equation applies only to:

 Spherical particles in a very dilute suspension (0.5 to 2 gm per

SUSPENSIONS
100 ml)

 Particles which freely settle without collision .

 Particles with no physical or chemical attraction.

225

Sedimentation Parameters

Sedimentation volume (F) or height (H) for

flocculated suspensions:
Definition:
SUSPENSIONS

Sedimentation volume is a ratio of the ultimate volume of

sediment (Vu) to the original volume of sediment (VO)
before settling.
F = V u / VO
Where,
Vu = final or ultimate volume of sediment
VO = original volume of suspension before settling
226
 F has values ranging from less than one to greater than one.

When F < 1 Vu < Vo

SUSPENSIONS
When F =1 Vu = Vo

The system is in flocculated equilibrium and show no clear

supernatant on standing.

When F > 1 Vu > Vo

Sediment volume is greater than the original volume due
to the network of flocs formed in the suspension and so
loose and fluffy sediment
227

The sedimentation volume gives only a qualitative account of

flocculation.
SUSPENSIONS

Fig : Suspensions quantified by sedimentation volume (f) 228

 Degree of flocculation (β)
It is the ratio of the sedimentation volume of the
flocculated suspension ,F , to the sedimentation volume
of the deflocculated suspension, F∞

SUSPENSIONS
ß = F / F∞

(Vu/Vo) flocculated
ß = --------------------
(Vu/Vo) deflocculated
The minimum value of ß is 1,when flocculated suspension
sedimentation volume is equal to the sedimentation volume
229
of deflocculated suspension.

2.Brownian Movement (Drunken walk)

 Brownian movement of particle prevents sedimentation

by keeping the dispersed material in random motion.
SUSPENSIONS

 Brownian movement depends on the density of dispersed

phase and the density and viscosity of the disperse medium.

 The kinetic bombardment of the particles by the molecules of the

suspending medium will keep the particles suspending, provided that
their size is below critical radius (r).

230
 Brownian movement can be observed,

 If particle size is about 2 to 5mm,

SUSPENSIONS
 When the density of particle & viscosity of medium are
favorable.

231

Brownian motion is given by equation: SUSPENSIONS

Where, R = gas constant

T = temp. in degree Kelvin
N = Avogadro‟s number
η = viscosity of medium
t = time
r = radius of the particle
232
3.Electro kinetic Properties

Zeta Potential

SUSPENSIONS
The zeta potential is defined as the difference in potential between the
surface of the tightly bound layer (shear plane) and electro-neutral
region of the solution.

233

SUSPENSIONS

 As the potential drops off rapidly

b at first, followed more gradual
decrease as the distance from the surface increases.

 This is because the counter ions close to the surface acts as a

screen that reduce the electrostatic attraction between the
charged surface and those counter ions further away from the
surface.
234
 Zeta potential has practical application in stability of systems
containing dispersed particles .

 Since this potential, rather than the Nernst potential, governs the
degree of repulsion between the adjacent, similarly charged,
dispersed particles.

SUSPENSIONS
 If the zeta potential is reduced below a certain value , the attractive
forces exceed the repulsive forces, and the particles come together.

 This phenomenon is known as flocculation.

235

 The flocculated suspension is one in which zeta potential of

particle is -20 to +20 mV.

 Thus the phenomenon of flocculation and de flocculation

SUSPENSIONS

depends on zeta potential carried by particles.

236
Deflocculation and flocculation
Flocculated Suspensions
 In flocculated suspension, formed flocs (loose aggregates) will cause
increase in sedimentation rate due to increase in size of sedimenting
particles.

SUSPENSIONS
 Hence, flocculated suspensions sediment more rapidly.

Here, the sedimentation depends not only on the size of the flocs but
also on the porosity of flocs.

237

Deflocculated suspensions

In deflocculated suspension, individual particles are

settling.
SUSPENSIONS

 Rate of sedimentation is slow , which prevents

entrapping of liquid medium which makes it difficult to
re-disperse by agitation.

This phenomenon called „caking‟ or „claying‟.

 In deflocculated suspension larger particles settle fast

and smaller remain in supernatant liquid so supernatant
appears cloudy.
238
 :
FORMULATION OF SUSPENSIONS

 The formulation of a suspension depends on whether the

suspension is flocculated or deflocculated.

SUSPENSIONS
 Three approaches are commonly involved

1. Use of structured vehicle

2. Use of controlled flocculation
3. Combination of both of the methods

239

Flow chart of formulation of suspension

SUSPENSIONS

240
 Structured vehicle

 Structured vehicles called also thickening or suspending

agents.

SUSPENSIONS
 They are aqueous solutions of natural and synthetic gums.

These are used to increase the viscosity of the suspension.

It is applicable only to deflocculated suspensions.

E.g. methyl cellulose, sodium carboxy methyl cellulose,
acacia, gelatin and tragacanth.
241

These structured vehicles entrapped the particle and

reduces the sedimentation of particles.
SUSPENSIONS

Thus, the use of deflocculated particles in a structure vehicle

may form solid hard cake upon long storage.

242
Too high viscosity is not desirable as:

a) It causes difficulty in pouring and administration.

b) It may affect drug absorption since they adsorb on the

SUSPENSIONS
surface of particle and suppress the dissolution rate.

 Structured vehicle is not useful for Parenteral suspension

because they may create problem in syringeability due to high
viscosity.

243

Controlled flocculation

° Controlled flocculation of particles is obtained by

adding flocculating agents, which are:
SUSPENSIONS

(1) electrolytes

(2) surfactants

(3) polymers

244
 Flocculation in structured vehicles

 Sometimes suspending agents can be added to

flocculated suspension to retard sedimentation

SUSPENSIONS
° Examples of these agents are:

Carboxymethylcellulose (CMC),
 Carbopol 934,
Veegum, and bentonite

245

SUSPENSIONS

INGREDIENTS FOR

FORMULATION OF SUSPENSIONS

246
.

Wetting agents They are added to disperse solids in continuous

liquid phase.
Flocculating They are added to floc the drug particles
agents
Thickeners They are added to increase the viscosity of
suspension.

Buffers They are added to stabilize the suspension to a

and pH adjusting agents desired pH range.

Osmotic They are added to adjust osmotic pressure

agents comparable to biological fluid.

Coloring They are added to impart desired color to

agents suspension and improve elegance.
Preservatives They are added to prevent microbial growth.

External They are added to construct structure of the 247

liquid vehicle final suspension.
SUSPENSIONS

Suspending agents

 Suspending agent are also known as hydrophilic colloids

which form colloidal dispersion with Water and increase the
viscosity of the continous phase.
SUSPENSIONS

Suspending agent form film around particle and decrease

interparticle attraction.

 Most suspending agents perform two functions

i.e. besides acting as a suspending agent

they also imparts viscosity to the solution.
248
 Preferred suspending agents are those that give thixotropy to the
media such as

SUSPENSIONS
Xanthan gum,
Carageenan,
Na CMC/MC mixers,
Avicel RC 591
Avicel RC 581 and
Avicel CL 611.
.

249

Stability pH range and concentrations of most commonly used suspending agents.

Suspending agents Stability pH Concentrations used
range as suspending
agent

Sodium alginate 4-10 1– 5 %

Methylcellulose 3-11 1– 2 %
SUSPENSIONS

Hydroxyethyl cellulose 2-12 1-2%

Hydroxypropyl cellulose 6-8 1-2%
Hydroxypropyl 3-11 1-2%
methylcellulose
CMC 7-9 1-2%

Colloidal 0-7.5 2- 4 %
silicon dioxide

250
List of Suspending Agents
Alginates
•Methylcellulose
•Hydroxyethylcellulose
•Carboxymethylcellulose

SUSPENSIONS
•Sodium Carboxymethylcellulose
•Microcrystalline cellulose
•Acacia
•Tragacanth
•Xantham gum
•Bentonite
•Carbomer
•Carrageen
•Powdered cellulose
•Gelatin 251

Alginates

 Alginate salts have about same suspending action to that

of Tragacanth.
SUSPENSIONS

 Alginate solution looses its viscosity when heated above 60ºC.

due to polymerization.

Alginate granules

252
  Maximum viscosity is observed at a pH range of 5-9 of
alginate.

 Chemically alginates are polymers composed of mannuronic

acid and glucuronic acid monomers.

 In practice, alginate is used at concentration less than 10 %

w/w, particularly at 5 % w/w.

253

SUSPENSIONS

Methylcellulose

 Methylcellulose is available in several viscosity grades.

 The difference in viscosity is due to difference in methylation

and polymer chain length.
SUSPENSIONS

 Methylcellulose is more soluble in cold water than hot water.

 Methylcellulose is stable at pH range of 3-11.

Methyl cellulose on on Solution form
Gel form
heating cooling

Methyl cellulose
powder
254
 Hydroxy ethylcellulose:

 Hydroxyethylcellulose (HEC) is another good

suspending agent having somewhat similar characteristics
to methylcellulose.

SUSPENSIONS
 In HEC hydroxyethyl group is attached to cellulose chain.

 Unlike methylcellulose, HEC is soluble in both hot and cold water

and do not form gel on heating.

255

Carboxy methylcellulose (CMC)

 Carboxy methylcellulose is available at different viscosity grades.

 Low, medium and high viscosity grades are commercially

SUSPENSIONS

available.

 In case of HV-CMC, the viscosity significantly decreases when

temperature rises to 40 ºC from 25 ºC.

 Therefore, to improve viscosity and stability of suspension MV-CMC

is widely accepted.

256
Microcrystalline Cellulose (MCC; Tradename-Avicel)

 It is not soluble in water, but it readily disperses in water to give

thixotropic gels.

 It is used in combination with Na-CMC, MC or HPMC, because

SUSPENSIONS
they facilitate dispersion of MCC.

257

The advantages of MCC:

 Alginate complex compositions are that they provide excellent

stability.
SUSPENSIONS

 Formulation of dry powder suspensions with MCC;

Alginate complexes produce an excellent dry readily hydratable

and dispersible formulation for reconstitution.

258
 Wetting Agents
 Hydrophilic materials are easily wetted by water while hydrophobic
materials are not.

 However hydrophobic materials are easily wetted by non-polar

SUSPENSIONS
liquids.

 The extent of wetting by water is dependent on the hydrophillicity of

the materials.

 If the material is more hydrophilic less difficulty in wetting by

water.

 The concentration used is less than 0.5 %.

259

Surfactants

 Surfactants decrease the interfacial tension between drug particles

and liquid thus liquid is penetrated in the pores of drug particle
displacing air from them and thus ensures wetting.
SUSPENSIONS

 Generally, we use non-ionic surfactants but ionic surfactants can

also be used depending upon certain conditions.

Polysorbate 80 is most widely used due to its following advantages

 It is non-ionic so no change in pH of medium

 No toxicity. Safe for internal use. 260
 Hydrophilic Colloids

 Hydrophilic colloids coat hydrophobic drug particles

in one or more than one layer.

SUSPENSIONS
 This will provide hydrophillicity to drug particles and facilitate
wetting.

 They cause deflocculation of suspension because force of

attraction is declined. e.g. acacia, tragacanth, alginates, guar
gum.

261

Solvents
 The most commonly used solvents used are alcohol,
glycerin, polyethylene glycol and polypropylene glycol.
SUSPENSIONS

 The mechanism by which they provide wetting is that they

are miscible with water and reduce liquid air interfacial tension.

 Liquid penetrates in individual particle and facilitates wetting.

262
n.

Buffers
Buffers are the materials which when dissolved in a
solvent will resist any change in pH when an acid or base is added.

 To encounter stability problems all liquid formulation should be

SUSPENSIONS
formulated to an optimum pH.

 Rheology, viscosity and other property are also dependent on the

pH of the system.

263

. Generally pH of suspension preferably at 7.4-8.4.

 Most commonly used buffers are salts of weak acids such as

carbonates,
citrates,
SUSPENSIONS

gluconates,
phosphate and tartrates.

264
 Osmotic Agents
 They are added to produce osmotic pressure comparable to
biological fluids when suspension is to be intended for
ophthalmic or injectable preparation.

SUSPENSIONS
 Most commonly used osmotic agents are

 dextrose,
 mannitol
 sorbitol.
 sodium chloride,
 sodium sulfate
 glycerol.

265

Preservatives

 Naturally occurring suspending agents such as tragacanth, acacia,

xanthan gum are susceptible to microbial contamination.
SUSPENSIONS

This leads to:

 loss in suspending activity of suspending agents,

 loss of color, flavor and odor,
 change in elegance etc.

266
 Name of preservatives Concentration range

Propylene glycol 5-10%

Disodium EDTA 0.1%

SUSPENSIONS
Benzalkonium chloride 0.01-0.02%
Benzoic acid 0.1%
Butyl paraben 0.006-0.05% oral
suspension
0.02-0.4% topical
formulation

Disodium EDTA benzalkanonium 267

Flavoring And Coloring Agents

 They are added to increase patient acceptance.

SUSPENSIONS

 Only sweetening agent are not capable of complete taste masking

of unpleasant drugs therefore, a flavoring agents are incorporated.

268
 Eg:

Acacia Ginger Sarsaparilla

syrup
Anise oil Glucose Spearmint oil

SUSPENSIONS
Benzaldehyde Glycerin Thyme oil

269

Coloring agents

 Colors are obtained from natural or synthetic sources.

Plant colors are most widely used for oral suspension.

SUSPENSIONS

 The synthetic dyes should be used within range of( 0.0005 % to

0.001%)

 Color aids in identification of the product.

 The color used should be acceptable by the

particular country.
270
Most widely used colors are as follows.

· Titanium dioxide (white)

· Brilliant blue (blue)

SUSPENSIONS
· Indigo carmine(blue)

· Amaranth (red)

Annatto seeds
· Tartarazine (yellow)
Annatto seeds(yellow to orange)
271

Sweetening Agents
They are used for taste masking of bitter drug particles.

Bulk sweeteners
SUSPENSIONS

 Sugars such as xylose, ribose, glucose, mannose.

 Sugar alcohols such as sorbitol, xylitol, mannitol

A bulk sweeteners is used at concentration of 15-70 %

272
 Artificial sweetening agents

•Sodium cyclamate

•Sodium saccharin

SUSPENSIONS
•Aspartame

273

Humectants
 Humectants absorb moisture and prevent degradation of API by
moisture.

Examples of humectants most commonly used in

SUSPENSIONS

suspensions are

 propylene glycol

glycerol.

Total quantity of humectants should be between 0-10 % w/w.

274
 Antioxidant
Ascorbic acid derivatives such as ascorbic acid, erythorbic acid,

Thiol derivatives such as thio glycerol, cytosine, acetylcysteine,

SUSPENSIONS
 Tocopherols

 Butylated hydroxy anisole(BHA)

 Butylated hydroxytoluene (BHT)

Sodium bi sulfite,

Sodium sulfateacetone
275

PREPARATION OF SUSPENSIONS

Following consideration are important for manufacturing

pharmacist
SUSPENSIONS

 Selection of right material that go into the manufacture.

 The step involved and their sequence in the manufacture.

 Preservation and storage of the product.

276
 Small scale preparation of suspensions:

Step 1:

SUSPENSIONS
Suspensions are prepared by grinding (or) levigating the insoluble

materials in the mortar to a smooth paste with a vehicle containing the

wetting agent.

277

Step 2:
 All soluble ingredients are dissolved in same portion of the
vehicle and added to the smooth paste to step1 to get slurry.
SUSPENSIONS

Step 3:

The slurry is transformed to a graduated cylinder, the mortar is

rinsed with successive portion of the vehicle.

278
 Step 4:
Decide whether the solids are
Suspended in a structured vehicle
Flocculated
Flocculated and then suspended

SUSPENSIONS
Add the vehicle containing the suspending agent (or) flocculating agent
Step-5
Make up the dispersion to the final volume .

Thus suspension is prepared.

279

Packaging of Suspensions

Introduction

 Pharmaceutical suspensions for oral use are generally packed

SUSPENSIONS

in wide mouth container having adequate space above the

liquid to ensure proper mixing.

 Parenteral suspensions are packed in either glass ampoules or

vials.

280
 Ideal Requirements of Packaging Material

 It should be inert.

 It should effectively preserve the product from light,

SUSPENSIONS
air, and other contamination through shelf life.

 It should be cheap.

 It should effectively deliver the product without any

difficulty.

281

Materials Used For Packaging

Generally glass and various grades of plastics are used in

packaging of suspension.
Glass
SUSPENSIONS

Generally soda lime and borosilicate glass are used

in preparation of non sterile suspensions.

282
 Amber glass doesn‟t allow U.V light to pass through.

 Amber characteristics can be developed in the

glass by addition of various types of additives.

SUSPENSIONS
Type of glass Additive giving amber
color
Soda lime FeO + sulfur (in
presence of reducing
agent)
Borosilicate FeO+TiO 2

283

Disadvantages of Glass Materials:

They are fragile.

SUSPENSIONS

They are very heavy as compared to plastic so

handling and transport is difficult.

 Most important disadvantage of glass that

glass constituents get extracted into the product.

284
Plastic
Due to the negative aspects of glass, plastic material

SUSPENSIONS
significantly use of plastic as packaging material for sterile as
well as non-sterile pharmaceutical suspension increased.

285

Advantages Of Plastic Material:

•Non breakability.
SUSPENSIONS

•Light weight.
•Flexibility.

Materials used: -

Polyethylene, PVC, polystyrene, polycarbonate etc

286
Closure And Liners

With an exception of ampoules all containers required

elastomeric closure.

SUSPENSIONS
.

closures

liners

287

Factors affecting in selecting closure:

Compatibility with product.

 Seal integrity.
SUSPENSIONS

It should be stable throughout the shelf life.

Factors affecting in selecting liner:

 Chemical resistance.
 Appearance
 Gas and vapor transmission.
 Removal torque.
 Heat resistance.
 Shelf life. 288
 Economical factors
 STORAGE REQUIREMENTS & LABELLING

Labelling:

SUSPENSIONS
Shake well before use

Do not freeze

Protect from direct light(for light sensitive drugs)

 In case of dry suspensions powder the specified amount of

vehicle to be mixed may indicated clearly on label.
289

Label:
SUSPENSIONS

290
 STORAGE :

 Suspensions should be stored in cool place but should not be kept

in a refrigerator

SUSPENSIONS
 Freezing at very low temperatures should be avoided which may
lead to aggregation Of suspended particles

0
Stored at controlled temperature from 20-25 c

291

SUSPENSIONS

292
 Evaluation of Suspensions

 Sedimentation method

SUSPENSIONS
 Rheological method

 Electro kinetic method

 Micromeritic method

293

Sedimentation method :

Two parameters are studied for determination of sedimentation.

SUSPENSIONS

1. Sedimentation volume,

2. Degree of flocculation.
,

294
Sedimentation volume

The suspension formulation (50 mL) was poured separately into

100 mL measuring cylinders and sedimentation volume was read
after 1, 2, 3 and 7 days, and thereafter at weekly intervals for 12 weeks.

SUSPENSIONS
 Triplicate results were obtained for each formulation.

Sedimentation volume was calculated according to the equation:

F = Vu/Vo
Where, F = sedimentation volume, Vu = ultimate height of sediment
and Vo = initial height of total suspension

295

Rheological method

 It provide information about Settling behaviour .

The arrangement of the vehicle and the particle structural

SUSPENSIONS

features.

 Brookfield viscometer is used to study the viscosity of the

suspension .
 It is mounted on heli path stand and using T-bar spindle.

T-bar spindle is made to descend slowly into the suspension

and the dial reading on the viscometer is then a measure of the
296
resistance the spindle meets at various level.
  This technique also indicates at which level of the suspension
the structure is greater owing to particle agglomeration.

 The dial reading is plotted against the number of turns of the

spindle.

SUSPENSIONS
 The better suspension show a lesser rate of increase of dial
reading with spindle turns, i.e. the curve is horizontal for long
period.

297

Electro kinetic method

 Measurement of Zeta-potential using Micro electrophoresis

apparatus & ZetaPlus (Brookhaven Instruments Corporation, USA).
SUSPENSIONS

It shows the stability of a disperse system.

Micro-Electrophoresis
Apparatus Mk I

ZetaPlus
298
Zeta potential

The zeta potential of the formulated suspensions was determined

using a ZetaPlus (Brookhaven Instruments Corporation, USA).

Approximately 1 mL of suspension was transferred into a plastic

SUSPENSIONS
cuvette using a pipette and diluted with distilled water.

 The Brookhaven zeta potential software was used for the

measurement .
Parameters set to a temperature of 250C and refractive index (1.33)

The zeta potential of the formulations was determined on day 0, 7,

14, 21 and day 28 post formulation.
299

Micromeritic method :

The stability of suspension depends on the particle size of the

dispersed phase.
SUSPENSIONS

 Change in the particle size with reference to time will provide

useful information regarding the stability of a suspension.

A change in particle size distribution and crystal habit studied by

 microscopy

 coulter counter method

300
PHOTOMICROSCOPIC TECHNIQUE

The microscope can be used estimate and detect changes in

particle size distribution and crystal form.

SUSPENSIONS
Rapid processing of photo micrographs is enhanced by attaching
Polaroid camera to the piece of monomolecular microscope

By using this photo micrographs we can

determine the changes in physical properties
and stability of suspensions.

301

FREEZE- THAW TEST

 Freeze-Thaw test conducted by placing the sample in a freezer
for 18 hours followed by thawing at room temperature for 4 to
6 hours.

Repeat the Freeze-Thaw cycle for up to 10 times.

SUSPENSIONS

This test is conducted to determine the tendency to crystallize or cloud)

Freeze-thaw testing freezer INNER CHAMBER

302
 pH MEASUREMENT

 The measurement and maintenance pH is also very important step in

the Quality control testing .

SUSPENSIONS
 Generally there are 2 different types of methods used in the
measurement of pH.

303

METHODS FOR pH MEASUREMENT:

 The simplest and cheapest is to dip a piece of pH paper into the

sample.
SUSPENSIONS

 The paper is impregnated with chemicals that change color and the
color may be compared to a chart supplied with the paper to give
the pH of the sample.

304
 If greater accuracy is required a pH meter should be
used.

SUSPENSIONS
 A typical pH meter consists of a special measuring glass
electrode connected to an electronic meter that measures and
displays the pH reading.

305

VISUAL INSPECTION:

 With visual inspection, the ingredients and the final

products are carefully examined for purity and for
appearance .
SUSPENSIONS

 Physical appearance of products for patient adherence

and compliance is critical so it should be:
Good looking
Elegance in appearance .

306
 DISSOLUTION STUDY OF SUSPENSIONS

Introduction:

SUSPENSIONS
The drug release from suspensions is mainly through dissolution.

 Suspensions share many physico-chemical characteristics of

tablet & capsules with respect to the process of dissolution.

 As tablets & capsules disintegrate into powder and form

suspensions in the biological fluids.

 So dissolution is carried as follows

307

Dissolution Testing

Official Method (Conventional Method):

 It is known as paddle method.

SUSPENSIONS

308
The apparatus consists of a cylindrical 1000- ml round bottom
flask in a multiple – spindle dissolution drive apparatus and
immersed in a controlled temp bath maintained

SUSPENSIONS
Dissolution profile of the 500 mg sample suspension is

 determined at 37°C in 900 ml of

 pH 7.2 phosphate buffer using

 the FDA paddle method at 25 RPM.

309

 The paddle should position to extend to exactly 2.5 cm

above the flask bottom.

 The suspension is to be introduced carefully into the

SUSPENSIONS

flask at the bottom using a 10- ml glass syringe with an

attachment 19-cm needle.

 Withdraw 5 ml of dissolution medium (and replace

with an equal volume of drug –free buffer) in a 5 ml glass
syringe.

 Immediately filter through a 0.2 µm membrane and

analyze.
310
 SUSPENSIONS
311

Innovations of suspensions

1. Nano suspensions
SUSPENSIONS

2. Taste masked pharmaceutical suspensions

3. Sustained release suspensions

312
 1. Nano suspensions:

 Nano suspensions are the biphasic colloidal dispersions

of nano sized drug particles stabilised by surfactants
without the matrix materials.

They can also be defined as a biphasic system consisting of

pure drug particles dispersed in an aqueous vehicle in which
the diameter of the suspended particle is less than 1 μm in
size.

313

SUSPENSIONS

SUSPENSIONS

314
 2.Taste Masked Pharmaceutical
Suspensions .

 Un-palatability due to bad taste is a major concern

in most of the dosage forms containing bitter drugs.

SUSPENSIONS
 In case of suspensions also taste masking is being applied to
mask bitterness of drugs formulated.

315

The taste masking approaches for suspensions are:

a. Polymer coating of drugs.

SUSPENSIONS

b. Encapsulation with basic drugs.

c. Polymer coating with basic substances.

d. Coating and pH control.

316
a. Polymer Coating of Drugs

The polymer coat allows the time for all of the particles to be
swallowed before the threshold concentration is reached in the
mouth and the taste is perceived.

SUSPENSIONS
The polymers used for coating are

•Ethyl cellulose
•Eudragit RS 100
•Eudragit RL 100
•Eudragit RS 30 D
•Eudragit RL 30 D

317

b. Encapsulation with a Basic Substance

Here a basic substance is mixed with a bitter tasting drug which is

insoluble at high pH.
SUSPENSIONS

The mixer is then encapsulated with a polymer (cellulose

derivative, vinyl derivative or an acid soluble polymer
Eg: copolymer of dimethyl ammonium methyl methacrylate).

The drug after encapsulation are suspended, dispersed or

emulsified in suspending medium to give the final dosage form.

318
 c. Coating and pH Control

Those drugs which are soluble at high pH are preferably be

maintained in a suspension at a low pH where the drug exhibit
maximum insolubility.

SUSPENSIONS
 Similarly drugs which are soluble at low pH are preferably
maintained in suspension at a high pH where the drug is insoluble.

Also applying polymeric coating to the drug substance avoids

solubilization of drug when administered providing taste masking.

319

Some Examples of Taste Masked Suspensions

Sr.No Name of the drug Taste masking approach

1 RISPERIDONE pH
control and polymer coating
(with Eudragit RS)
SUSPENSIONS

2 DICLOFENAC Polymer
coating with Eudragit RS
100

3 LEVOFLOXACIN Polymer
coating (Eudragit
&cellulose acetate,)

320
 Sustained Release Suspensions

 Sustained release is a method to increase only the duration of

action of drug being formulated without affecting onset of
action.

SUSPENSIONS
 In suspension sustained release affected by coating the drug to be
formulated as suspension by insoluble polymer coating.

 The polymer coating provides sustained release and also masks

the taste of the bitter drug.

321

 The polymer used for sustained release in suspension is

as follows as
 Ethyl cellulose,
Eudragit,
Cellulose acetate, etc.
SUSPENSIONS

 The main advantage of sustained release

suspension is decrease in dosing frequency.

322
Approaches used in formulation of sustained release oral suspensions

1. Ion exchange resin.

2. Microencapsulation technique

SUSPENSIONS
3. Saturated drug suspension as a suspending medium.

4. Using non aqueous vehicle.

5. Reconstitution.

6. Protective coating.

323

REFERENCES
 Subramanyam C.V.S., Second edition, “Suspensions” Text
Book of Physical Pharamaceutics, PageNo. 374-387.
SUSPENSIONS

 Ansel C., Allen L.V., Popovich N.G. Eighth edition

“Disperse systems” Pharmaceutical Dosage Forms & Drug
Delivery Systems, Lippincott Williams and Wilkins,
Philadelphia 2005, Page No. Page No. 387-389, 398.

324
  Cooper & Gun, Sixth edition, “Dispersed system” Tutorial
Pharmacy, Page No. 75-78.

SUSPENSIONS
 Aulton M.E. Second edition, “Suspension” Pharmaceutics-
The Science of Dosage Form Design, Churchill Livingstone,
Edinburgh 2002, PageNo. 84-86, 273.

325

 Martin A. Fourth edition, “Coarse dispersion”

Physical Pharmacy, Lippincott Williams and Wilkins,
Philadelphia 2001, Page No. 479-481.
SUSPENSIONS

 Remington, Twentieth edition, “Colloidal

Dispersions” The Science and Practice of
Pharmacy, Lippincott Williams and Wilkins,
Philadelphia 2000, Page No. 298-307.

326
SUSPENSIONS
327