Transcript 2. Additives

MONOPHASIC LIQUID
DOSAGE FORMS
SOLUTION:



“A solution is a liquid-preparation that contains one or
more soluble chemical substances dissolved in a specified
solvent.”
Advantages
Immediately available for absorption
Useful for hygroscopic drugs which must be
administered as a solution
Disadvantages
Less stable Incompatibility is faster
Bacterial contamination
Solvents used
A. Aqueous liquids:
Water
Purified Water
Water for injection
Sterile water for injection
Bacteriostatic water for injection
B. Oils &oily materials:
Animals source…pig fat
Vegetable Source…corn,cotton
Mineral Source…liquid paraffin
Synthetics….ethyl oleate
C. Hydroxylated Compounds:
Ethanol
Propylene Glycol
D. Hydro-alcoholic Mixtures
E. Modern Vehicles:
Dioxalanes Solvent for aerosol sprays
Dimethylecetamide
-Vehicle for the internal Use
1. Purified Water
2.Aromatic Water
a. Chloroform Water
b. Peppermint Water
c. Cinnamon Water
d. Dill Water
- vehicles for external use
Isopropyl myristate
Liquid Paraffin
-vehicles for extraction
Isopropyl Alcohol
Acetone
Formulation Consideration

1) Solubility
a) pH
b) Cosolvency
c) Solubilization
d) Complexation
e) Hydrotrophy
f) Chemical modification of the drug molecule
2) Preservation
a) Preservatives
b) Antioxidants
c) Reducing agents
d) Synergists
3) Organoleptic consideration
a) Sweetening agents
b) Flavoring agents
c) Coloring agents
d) Viscosity control
e) Overall appearance
4) Stability
a) Chemical stability
b) Physical stability
1.SOLUBILITY

Expression of solubility
According to Indian Pharmacopoeia
Descriptive Phrase
- Approximate quantities(ml) of
solvent by volume for 1 part (1 gm) of solute by weight
Very soluble
- less than 1 part
Freely soluble
- from 1 to 10 parts
Soluble
- from 10 to 30 parts
Sparingly soluble
- from 30 to 100 parts
Slightly soluble
- from 100 to 1000 parts
Very slightly soluble
- from 1000 to 10,000 parts
Practically insoluble
- more than 10,000 parts
a. pH
A large number of drugs are either weak acids or weak bases. The
solubility of these agents can be markedly influenced by the pH
of the environment

Weak Acid
pH = pKa + log (ionised ) /(un ionised)
pH = pKa + log (base) / (acid)
Weak Base
pH=pKa +log (unionised) / (ionised)
pH = pKa+ log( base )/(acid)
b. COSOLVENCY
Weak electrolytes and nonpolar molecules frequently
have poor water solubility. These types of solutes are
more soluble in a mixture of solvents than in one solvent
alone. This phenomenon is known as cosolvency.
c. DIELECTRIC CONSTANT
One property of a solvent system is its dielectric
constant. The dielectric constant of a solvent can
be defined as the ratio of the capacitances of a
capacitor filled with the solvent and air
respectively.
d. SOLUBILIZATION
spontaneous increase of solubility of a poorly water-soluble
solute molecules into an aqueous solution of surface active
agents (or surfactants) in which a thermodynamically stable
solution is formed.
e. COMPLEXATION
Solubility of a compound may be increased by
complexing with a complexing agent. e.g.
solubility of para amino benzoic acid (PABA) may
be increased by complexing with caffeine
f. HYDROTROPHY
The term hydrotrophy has been used to designate the increase in
solubility in water of various substances due to the presence of
large amounts of additives.
g. CHEMICAL MODIFICATION OF DRUG
Poorly soluble drugs are chemically modified into water soluble
derivatives.
2.PRESERVATION
a.Preservatives
Some pharmaceutically useful preservative
Class -------Preservative ------Usual concentration (%)
-Acidic
Phenol
- 0.2 - 0.5
Chlorocresol
- 0.05 - 0.1
-Neutral
Chlorbutanol
Benzyl alcohol
- 0.5
- 1.0
-Mercurial
Thiomersal
Nitromersol
-
0.001 - 0.1
0.001 - 0.1
-Quarternary ammonium compounds
Benzalkonium chloride - 0.004 - 0.02
Cetylpyridinium
- 0.01 - 0.02
b. Antioxidants
An antioxidant is a molecule that inhibits
the oxidation of other molecules
c. Reducing agent
A reducing agent (also called a reductant or reducer) is the
element or compound in a reduction-oxidation reaction that
donates an electron to another species however, since the
reducer loses an electron we say it is "oxidized". This means
that there must be an "oxidizer"; because if any chemical is an
electron donor (reducer), another must be an electron recipient
(oxidant).
3.ORGANOLEPTIC ADDITIVES
a. Colouring Agents

Colouring Agents generally used in case of cosmetic
preparations.

The second reasons is to distinguish one product from the
products. A third reason is to distinguish the preparation being
administered

Classification1.natural colouring agents-plant
-animal
-minerals
2.syntetic
-coal tar
1. Natural Colouring Agents:

Plants:

Many plants contain colouring agents which may be
extracted. and used as colorant.

Some Examples are:
a. Chlorophyll-green
b. Annatto seeds-yellow to orange
Animal:
- Cochineal:
It is an alkaline solution of the soluble Colouring principles
caraminic acid of cochineal insects preserved by the addition of.
It is very dark purplish red liquid.
Minerals:
-Mineral colours are termed pigments.
-They are used to colour lotions, cosmetics and other preparation for
external application.
-As they are toxic, their use for internal preparation is forbidden.
Ex:
Red ferric oxide
Yellow Ferric Dioxide
2. Synthetic colouring agents

The synthetic colours are coal tar dyes, because many of them
are produced from substance obtained from coal-tar.

The certified colours are classified into three groups:

Group I- F.D. and C. Colours used in foods, drugs and
cosmetics.

Groups II- The D. and C. Colour used in drug and Cosmetics.

Group III- The External D. and C. Colour.
b. Flavouring agents
The use of flavour is actually a composite sensation of taste,
touch, smell, sound and heat.
 There are simply four types of tastes
- Sweet
- Sour
- Salty
- Bitter .
Similarly there are seven basic odours like
- Ethereal , camphoraceous ,Musky, Floral ,Pepperminty
,Pungent ,Putrid

Classification of flavouring agents
Two Types:
1. Natural and
2. Synthetic
1. Natural
a. Fruits (Sweet, Sur and Astringent)
Citrus Fruits (Orange, Lemon)
b . Seeds (Vanilla, Anise, Nutmeg)
2.synthetics
Benzaldehyde
- Bitter Almond, Cherry pits
Decyl Aldehyde
- Citrus Flavours (Orange)
Cinnamic aldehyde - Cinnamon type
c. Sweetening agents







Sucrose
Sorbitol (Half Sweet than Sucrose)
Glycerin
Honey
Saccharin Sodium (300-550 times)
Cyclametaes (30 times sweeter than sucrose)
Aspartame
d.Viscosity control
Used to increase palatability and pourability
Examples of viscosity controlling agents are
-PVP
-cellulose derivatives
e.General apperance
depends on colour and clarity
4.STABILITY
a. Chemical stability
Ex- effect of amino acids on stability of aspirin in
propylene glycol solutions.
b. Physical stability
Oral liquids are stable if it retains
viscosity,colour,taste and odour throughout its shelf
life
liquid dosage forms
Monophasic (homogeneous solutions in which solute and
solvent cannot be differentiated)
Emulsions
External
Internal
Draughts
Drops
Linctus
Syrups
Elixirs
mixtures
Biphasic
Liquids for
oral cavities
Gargles
Liquids appiled
on body cavities
Douches
Mouthwashes
Enemas
Throat paints
Ear drops
Glycerites
Nasal drops
Throat spray
Inhalants and eye drops
suspensions
Liquids appilied
on skin
Liniments
Lotions
collidions
ORAL MONOPHASIC DOSAGE FORM

ORAL MONOPHASIC DOSAGE FORM
Draughts
Drops
Linctuses
Syrups
Elixirs
Mixtures
A. Draughts




It is simple solution (mixture) which contains a single dose.
Each dose is sent in separate bottle.Total volume is 50 ml.
It is essential to be labelled with storage conditions on
draughts.
It is given very early expiry date (48 hours).
Examples:
1.Ipecacuanha emetic draughts-BPC (Treatment of poison)
2. Paraldehyde draughts- Oxidized to
acetic acid and cause death
Do not use, if the solution is discolored.
B. Drops:
. For
vitamins and antibiotics formulation for pediatric purpose.
. It is not meant for higher dose.
. Drops are dispensed in a bottle with dropper.
. It contains potent drugs, so dose is measured precisely.
C. Linctuses





Viscous liquid oral preparations that are usually prescribed for
the relief of cough.
Consists of simple solution of active agent in high conc of
sucrose.
Vehicle is always a syrup and sometimes contains glycerin,
because of sweetening taste and soothing effect on mucous
membrane.
Should be taken as such without dilution and sipped slowly to
prolong action of drug
EXAMPLE OF LINCTUSES: Codeine Linctuses
Diamorphine Lictus
Compound Tolu Linctus
FORMULATION OF LINCTUSES





1. Vehicle
2. Additives
1. Vehicles:
a. Syrup
b. Tolu Syrup
It also provides aromatic odour and flavour, it has also mild
expectorant action.
Due to high content (68%) of sucrose, solution tends to
crystallise, so stored at constant temperature.
Due to high solid and low water content, dissolution of
medicament is slow. Sometime glycerol is used as Auxiliary
Vehicle.
2. Additives
A. Chemical Stabilizers :
Linctuses are self stabilized due to syrup, so no need of
any other stabilizer.
B. Colouring Agent:
Coal-tar dyes
Ex: Compound Tartrazine solution
C. Flavouring Agent:
Syrup itself act as masking agent. Some fruit flavours used
are;
Lemon and Black current
D. Preservatives: Syrup has preservative action due to high
osmotic pressure.
Tolu syrup contain Benzoic acid and cinnamic acid.Some
other preservatives are -Chloroform spirit -Benzoic acid
spirit solution
D . SYRUPS:




“It is concentrated aqueous solution of sucrose mixed with
solution of medicaments and others additives.”
Generally syrup is prepared by sucrose but is partly replaced
by dextrose or other polyhydric alcohols to reduce
crystallisation of sucrose or to increase solubility of
medicaments and other additives.
Consists of 85% sugars
2 types of syrups
Non medicated syrup
Medicated syrup
FORMULATION OF SYRUP
Sugar-85%
 Anti microbial preservatives(0.1-0.2%)
benzoic acid ,sodium benzoate
 Flavorant
 colorant
ExampleActive drug
– 5ml

Other drug solids
-3ml
Glycerin
- 15ml
Sucrose
-25g
Ethanol
- 95%qs
Purified water
- 100ml
Function of Syrups






Sweetening agent
Good antioxidant
Preservatives
Demulcents and
soothing agent
EXAMPLES OF SYRUPS:
Codeine phosphate syrup
Squill syrup
Syrups are used for formulating
Antibiotics
Antitussives
Antihistamines
Vitamins
Analgesic/antipyretic
PREPARATION OF SYRUP –
1.Solution with heat: For non-volatile, thermostable drugs
2.Agitation without heat: For volatile, thermolabile drugs
3.Addition of medicating liquid to syrup: For liquid
medicaments such as extracts, tinctures
4.Percolation:
E. ELIXIRS
Elixirs are clear, pleasantly-flavoures, sweetened
Hydroalcoholic liquid intended for oral use.
2 types of elixirs
medicated elixir
non medicated elixir
ADDITIVES
1.Chemical Stabilizers: pH Adjustment
Sequestering agents- like EDTA
2.Colouring Agents: Amaranth
Compound Tartrazine
3.Flavouring Agents: Lemon spirit ,Compound orange spirit
4.Sweetening Agents: Invert Syrup, Sodium Sachharin
5. preservatives: 20% Alcohol as vehicle
Propylene glycol
Formulation of phenobarbital elixir
phenobarbital
-
4g
orange oil
-
0.25ml
propylene glycol -
100ml
alcohol
-
200ml
sorbitol solution -
600ml
colour
-
purified water
-
EXAMPLESChloral Elixir
pediatric Paracetamol Elixir
Ephedrine Elixir
Phenobarbitone Elixir
qs
1000ml
F.MIXTURES
“Mixtures are a liquid preparations, intended for oral
administration, in which drug is dissolved, suspended or
dispersed in a suitable vehicle.”
Classification:
Simple Mixture
Indiffusible Mixture
Diffusible Mixture
Precipitates forming liquids Mixture
containing slightly soluble liquids
Miscellaneous
Formulation:
1. Vehicles: Camphor water
Caraway water
2. Medicament
3. Preservatives: Chloroform water-0.25%
Benzoic acid-0.1%
4. Colours and Flavours:
Aromatic water Syrups
lemon syrup orange syrup
5. Container: - Plain glass or plastic bottle
6. Thickening Agent: (For indiffusible Mixtures)
a. Poly Saccharides
Natural - Acacia
Starch
Semisynthetic - Methyl Cellulose
Hydroxy ethylcellulose
b. Inorganic Agents:
Clays - Bentonite
Syntheitc - Carbomer
Preparation of Suspending Agent:
A. Compound powder of Tragacanth (C.P.T.)
Formula: Acacia
- 20%
Tragacanth - 15%
Starch
- 20%
Sucrose - 45%
It is used as such 2 gm per 100 ml. The compound of tragacanth is always
used when the vehicle is other than water or chloroform water.
B. Mucilage of Tragacanth (M.T.)
Formula: Tragacanth finely powdered -12.5 gm
Alcohol (90%)
- 25 ml
Chloroform Water Q.S. - 100 ml
It is used as mucilage-1/4 th of the mixture. The mucilage of tragacanth is
used when vehicle is water or chloroform.
Liquids for Special Use (Oral Cavity)





Gargles
Mouth-washes
Throat paints
Glycerites
Throat Spray
A. Gargles:
-Gargles are aqueous clear solutions intended to be used in the
mouth and throat.. Gargles are pleasantly flavoured and 5-9.5
pH appear to be safe.
-Some therapeutic agents used in gargles are antibiotics,
antiseptics , local anesthetics,Analgesic, Deodorants and
Astringents.
Examples:
Phenol gargles
Potassium chlorate and phenol gargles
Thymol glycerin compound
B. Mouth Washes
- Mouth washes are aqueous solution used to cleanse and
deodorise the buccal cavity.
- used for its deodorants, refreshing or antiseptic property.
Mouth washes generally contain antibiotic agents or astringent
,alcohol, glycerin, sweeteners and surfactants, flavouring and
coloring agents.
Examples: Alkaline phenol mouth wash
Hydrogen peroxide mouth wash
Buffer sodium perborate mouth wash
Compound sod. Chloride mouth wash
C. Throat Paints
Throat paints are liquid preparations applied to mucous
surfaces.
 They may be aqueous or alcoholic solution more viscous due
to high content of glycerin and prolong the action of
medicaments.
 Throat paints are used for the mouth and throat infection.
 contains – antiseptic, astringent and analgesic.
CONTAINERS: Dispensed in wide
mouth bottle with brush.
EXAMPLES:
Compound iodine paints
Crystal violet paint

D. Glycerites




These are viscous hygroscopic liquids or semisolids
preparations which contain not less than 50% by weight of
glycerin and dissolved medicaments.
Glycerites have sweet taste and does not become rancid. They
also act as preservatives.
Glycerites are hygroscopic and should be preserved in air
tight container.
EXAMPLES:
Borax glycerin - Used as bacteriostatic
Phenol glycerin - Mouth ulcer
Tannic acid glycerin - in ulcer
E. Throat Spray




Spray solutions are aqueous alcoholic or glycerin solution
intended for throat or nose by means of atomizer or nebulizer.
The spray device should produce coarse droplets for upper
respiratory tract, while fine droplets for lungs (produced by
nebulizer).
Spray solution contain antibiotics, antihistaminic,
vasoconstrictors, alcohol and suitable solubilizing and wetting
agents. Spray solution contain chlorbutol as an antibacterial
and antifungal agent.
EXAMPLES:
Adrenaline and
Atropine spray compound-BPC.
LIQUIDS FOR SPECIAL USE (OTHER THAN
ORAL CAVITY):






DOUCHES
ENEMAS
EAR-DROPS
NASAL DROPS
INHALANTS/SPRAY/AEROSOLS
Eye drops
A. Douches








Douches is medicated aqueous solution for rinsing body cavity
applied at lower pressure like
Eye douches
Pharyngeal douches
Nasal douches
Vaginal douches
Bladder douches
Rectum douches
Generally three cavities are widely used ;
For vaginal purpose termed as Douches
For bladder purpose termed as Irrigation
For rectum purpose termed as Enemas.
-Douches
are restricted to vaginal solution have cleansing
or antiseptic action.
-Promote healing or as an astringent.
-Vaginal douches must be sterile if used after child birth
or surgery. -Bladder irrigation must always be sterile
as bladder is a sterile organ. Vaginal douches are
introduced by means of a suitable rubber syringe. have
pH 5.5
-Douches dispensed as concentrated forms and directions
for dilution with warm water.
Category Ingredients
1. Cleansing
-Isotonic sodium chloride solution
-Boric acid (2%)
-Sodabicarb (1-2%)
- Saponated cresol (0.2-.05%)
2. Antiseptic
Chlorhexidine (0.02%)
Chlorxylenol (5-10%)
Lactic acid (0.5-2%)
Mercuric chloride (0.001%)
KMnO 4 (0.001-1%)
3. Astringent
- Alum (1%)
Tannic acid Zinc sulphate
B. ENEMAS


“Enemas are aqueous or oily solution or suspension or oil in
water emulsion introduced into rectum or colon for cleansing ,
therapeutic or diagnostic purpose.
Types of Enemas:
1.Cleansing enemas
2.Therapeutic enemas.
3.Diagnostic enemas
4. Disposable Enemas
1.CLEANSING ENEMAS: Cleansing enemas used to
evacuate feaces in constipation or before an operation.
Two types:
A. By stimulating of peristalsis
i . Large volume: Plain water Soft soap Turpentine
enemas
ii. Small volume (Osmotic retention)
Sodium phosphate enema
Magnesium sulphate enema
Sorbitol Sodium chloride
Sodabicarb
B. By lubricating impacted feaces:
Olive oil enemas
Araches oil Enemas
Glycerin enemas
2.THERAPEUTICS ENEMAS:
Category
Ingredient
a. Sedative
Chloral hydrate Paraldehyde
b.Anthelmintics
Quassia
c. anti-inflammatory
Corticosteroids
d. nutrients
3.Diagnostic enemas:
It is used for X- Ray Examination of lower bowel.
Ex: Barium sulphate enemas.
4.Disposable Enemas
Enemas available in disposable plastic bags.
They include
evacuant enemas like magnesium sulphate
retention enemas of prednisolone .
CONTAINERS: Single use plastic pack with rectal nozzle
LABEL: To be warmed to body temperature before use
C. Ear Drops:
Ear drops are solutions or suspension of drugs that are
used into the ear. VEHICLES: - Water ,Propylene
glycol,glycerin , PEG-4000 ,Dil. Alcohol ,Haxylene glycol
uses
category
1. For mild infection
Antibiotics, anti bacterial
2. For softening
wax Hydrogen peroxide,
sodabicarb
3. For cleansing
Spirit
4. Drying weeping surface Astringent, ammonium
acetate
5. antiseptic- anaesthesic
phenol
CONTAINERS: Coloured fluted glass bottle with
dropper
LABELLED: - not to be taken
orally Store in a cool place
Not to be diluted
List of official ear drops:
Chloramphenicol ear drops
Hydrocortisone.
Hydrogen peroxide E.D.
Phenol E.D.
Sodium Bicarbonate E.D.
D.NASAL DROPS
“Nasal drops are liquid preparation and may be aqueous or oily
for instillation into nostrils.”
The following category can be formulated for nasal drops: sympathomimetics ------- vasoconstrictor (ephedrine)
Anti niflammatory ------ corticosteroids
Anti bacterial
Anti histamine
Local anaesthetics
Nasal Vehicles: they should possess following properties:
- pH range of 5.5-7.5.
- Have mild buffer capacity.
- Tonicity equivalent to normal saline.
- The viscosity should not exceed the normal viscosity of
nasal mucus.
Contain antimicrobial agents
Containers : Fluted color glass bottle with plastic screw cap and
dropper.
Label: -FOR EXTERNAL USE ONLY - STORE IN A
COOL PLACE
E. Nasal inhalation





Inhalation are solution or suspension of volatile aromatic
medicaments in alcohol, or an alcoholic preparation. And the
vapour of which is inhaled to lower respiratory tract.
If the ingredient is volatile at room temperature, it may be
placed on an absorbent pad and inhaled.
If not, poured on hot surface of water (65 C) and vapour is
inhaled.
Inhalation which requires hot water consists alcoholic solution
mixture of medicaments with water and light magnesium
carbonate.
Containers: White fluted bottle
Label: SHAKE BOTTLE BEFORE USE
Examples:
Benzoin inhalation
Menthol and benzoin inhalation
Menthol and eucalyptus inhalation
Epinephrine inhalation.
Nasal Sprays




Spray solutions are aqueous alcoholic or glycerin solutions
in the form of coarse droplets of finely divided solids
intended to be applied to the nose or throat by means of
atomizer.
The type of atomizer used depends upon the viscosity of
the spray solution.
Oily solutions were formerly used, but are no longer used
as they retard ciliary action and enter in
trachea and cause lipoidal pneumonia.
Examples:
Anti inflammatory (corticosteroids)
Antihistaminics
--Sympathomimetics
Local anaesthetics -- Antimigraine
F. EYE DROPS





Sterile, aqueous/oily solutions or suspensions intended for
instillation in eye sac.
Eye drops may contain buffers, stabilizing agents, dispersing
agents, solubilizing agents, anti-oxidants & agents required for
tonicity/ viscosity adjustment.
Single dose container should not contain anti-microbial
preservative.
In case of multi dose container a dropper should be supplied
with it for administration.
Maximum size of such containers is 10 ml.
LIQUIDS FOR EXTERNAL USE



LINIMENTS
LOTIONS
COLLODIONS
A. LINIMENTS








“Liniments are fluid, semi-fluid or occasionally semisolid
preparations intended for external application.”
They may be alcoholic or oily solution or emulsion.
Liniments containing substances have following
properties.
Analgesic
Rubefacient
Counter Irritants
Soothing
Stimulating
In case of monophasic (solution) liniments
two types of solvents are used.
1. Alcohol - Soap liniment
- Aconite liniments.
2. Oil
- Camphor Liniments
- Methyl Liniments
- Arachis and cotton seed oil is used. It is less irritant than
alcohol. It is spread more easily.
-Liniments may be applied with or without friction. It
may be painted or applied on skin by brush.
- Liniments should not be applied on broken skin.
- Liniments contains volatile ingredients
so cold storage is necessary and kept away from flame
PREPARATION: It can be prepared as solution or
emulsion as the case may be.
CONTAINER: Coloured fluted bottle.
LABEL: FOR EXTERNAL USE ONLY NOT FOR
BROKEN SKIN STORE IN COOL PLACE
INFLAMMABLE
B. LOTIONS




“Lotion are liquid preparations intended for external
application or for special use.It may be aqueous or alcoholic
solution or suspension referred as SHAKE LOTION.
In aqueous or alcoholic solution, the main ingredients are salts.
Alcohol causes defatting, countered by addition of castor oil.
Sometimes salt dissolved in water- aqueous solution, termed
as EYE-LOTION, meant for eyes.
-On
application of shake lotion on skin, the water
evaporates, leaving residue of medicaments on skin.
- The evaporation causes cooling effect.
-Lotions are applied to inflammed area.
-The use of alcohol hasten (faster) drying and enhance
cooling.
- The use of glycerin keeps skin moist and promote
adherence of residue powder on skin.
- The suspending agent like Na C.M.C. may be used to
assist dispersion.
-Lotion liable to microbial growth, so includes proper
preservatives. Lotion used for local cooling, soothing,
protective, drying or moisturizing properties.
Lotion includes- antifungal, anti-inflammatory, antiinfective, anti pyretic and local anesthetic agents.
EXAMPLES:
Lead lotion - lead subacetate in water
Salicylic lotion - salicylic acid in alcohol
CONTAINER: Fluted bottle, closed with plastic screw
cap.
LABEL: FOR EXTERNAL USE ONLY
DILUTED LOTION NOT TO BE USED LATED THAN
ONE MONTH AFTER ISSUE.
C. COLLODION







Collodions are fluid- prepared for external use.
They are applied by brush, rod or applicator.
The base is pyroxillin (Nitro Cellulose) in a volatile
solvents.
The volatile vehicle evaporates leaving a flexible,
protective film covering the site.
The volatile vehicles are ether, alcohol and acetone.
Flexibility to film given by castor oil.
Pyrocillin is highly inflammable so it is kept moist with
industrial menthylated spirit, stored loosely packed, protect
from light in a cool place.
EXAMPLES:
Flexible Collodion
–USP/BP
Salicylic acid collodion -BPC
LABEL: FOR EXTERNAL USE ONLY
STORE IN A COOL PLACE
HIGHLY INFLAMMABLE KEEP AWAY FROM
NAKED FLAMES.
MANUFACTURING CONSIDERATION
-Raw materials
-equipments
-Cleaning of equipments
-Material of construction
-compounding proceduce
RAW MATERIALS
1. Incoming raw materials should be tested
against some specifications regarding identity,
purity, uniformity and freedom from excessive
microbial contamination.
2. Additional processing may be required e.g. sizereduction or sterilization before manufacturing.
3. In oral liquid preparations water is the main
vehicle. It should meet the USP requirements for
Purified water. It may be obtained by distillation or
ion-exchange treatment
EQUIPMENTS
The following types of equipments may be used in
the manufacture of oral liquid solutions:1. Mixing tanks (SS 316 Stainless Steel) equipped
with an agitator.
2. Measuring devices for large and small amount
of solids and liquids.
3. A filtration system for the final polishing - e.g.
Sparkler filter.
CLEANING OF EQUIPMENTS
-All equipments must be thoroughly cleaned and
sanitized before use.
Disinfectants used: Dilute solutions of H2O2,
phenol derivatives and paracetic acid.
Sterilized by: Alcohol, boiling water, autoclaving,
steam or dry heat.
Material of construction
· Tanks are usually constructed of polished
stainless steel and are usually jacketed to allow
for heating or cooling of the contents.
· Tanks are covered and equipped with seethrough charging ports and illumination for easy
observation of the contents
· The compounded liquid may then be transported
to the filling line, either manually by filling into
portable transport tanks (fitted with wheels) or by
pumping (or gravity flow) through a liquid delivery
conduit.
COMPOUNDING PROCEDURE
Objective Complete solution should usually be
confirmed at every stage in the manufacture of a
homogeneous liquid.
Formula1. Active constituent / Drug
2. Vehicle (Water / Alcohol / Glycerol)
Sweetening agents (viscosity building agents)
Syrup, Sorbitol, Glycerol
3. Preservatives
4. Flavors
5. Colors (Dyes)
Steps of preparation
1. Purified water is heated to approximately 50 degrees to
facilitate the dissolution of the solid solutes. Solid solutes
are added to the warm water.
2. If any additive is required in small amount then it should
be dissolved separately and then mixed with the bulk
mixture.
3. Any large volume liquids (e.g. glycerol) are added and
mixed until homogeneous.
4. Before adding flavors the temperature should be reduced
to 30degrees(since most of the flavors are volatile). The
flavor should be dissolved in small amount of alcohol (since
flavors are generally insoluble in aqueous medium) and then
it is mixed with the bulk mixture.
5. Dye should be dissolved n small amount of water. Then
transferred to the bulk mixture.
6. Finally volume is made up to the required volume. The
total mixture is agitated thoroughly until homogeneity is
obtained.
7. Finally the batch is filtered to obtain a polished, clear
solution
PAKAGING MATERIALS
a. glass
b. plastic
Plastic containers
Glass containers
FILLING
3 basic filling methods
- gravimentric
- volumentric
- constant level filling
Liquid Filling System
Top filling
Palletized filling
Bottom filling
CONCLUSION

As it is easy to administer for children and elderly people and
also good compliance due to flavour,rapid absorption as it
avoids first pass effect and flexible dosing it is preffered.
REFERENCES
-The theory and practice of industrial pharmacy .
leon lachman and lieberman.
-Ansel’s pharmaceutical dosage forms and drug delivery
systems
-Dispensing pharmacy cooper and gunns
-Aulton.