Monophasic Liquid
Dosage Forms
Contents of
This Chapter
• Theoretical aspects including commonly used vehicles,
essential adjuvants like stabilizers, buffers, organoleptic additives with
examples.
• Study of Monophasic liquids like syrups, elixirs, linctuses,
solutions, gargles, mouthwashes, throat paint, eardrops, nasal drops, ear
drops, liniments, lotions, enemas, douches and collodions
Learning
Objectives
At the end of this
lecture, student will be able to
• Classify liquid dosage forms with examples
• Explain the formulation of monophasic liquid dosage forms
• Suggest suitable techniques for increasing solubility of a
poorly water soluble drug
• List out monophasic liquid dosage forms used internally
• Define various dosage forms
• Differentiate syrups and elixirs
• Explain the formulation of syrups, elixirs and linctuses
• List out the labelling details
• Give examples of monophasic liquid dosage for internal use
• List out monophasic liquid dosage forms used externally
• List out monophasic liquid dosage forms used in the oral
cavity
• Define various liquid dosage forms
• Differentiate gargles and mouthwashes
• Differentiate liniments and lotions
• List out the auxiliary labelling instructions
• Give examples of monophasic liquid dosage used externally
and in the oral cavity
• List out monophasic liquid dosage forms used in body
cavities
• Define various liquid dosage forms used in body cavities
• Differentiate douches and enemas
• List out types of enemas
• Explain the method of usage of douches and enemas
• List out the auxiliary labelling instructions
• Give examples of monophasic liquid dosage used in body
cavities
Liquid
Dosage Forms
– Monophasic Liquid Dosage Forms (single phase)
– Biphasic Liquid Dosage Forms (two phases)
Monophasic
Liquid Dosage Forms – Solutions
Solute + Solvent à
Completely soluble
Advantages
1. Uniformity of
dosage is ascertained
2. Faster absorption
leading to quick onset of action
3. Pleasing
appearance leading to enhanced patient compliance
Disadvantages
1. They are less
stable than solid dosage form
2. Unpleasant
flavors can be difficult to mask
3. Solution is bulky
to carry
4. Need of a dropper or measuring device to administer the
dose
5. Accidental
breakage leads to total loss of contents
Classification
of Monophasic Liquid Dosage Forms
1. Internal
2. External
3. Parenteral (Sterile dosage forms)
Internal: Syrup,
Elixir, Simple mixture, Draught, Paediatric drops, Linctus
External
Topical use: Liniments, Lotions, Collodions
Used in oral cavity: Gargles, Mouthwashes, Throat paints, Mouth
sprays, Throat sprays
Instilled into body cavity: Douches, Enemas, Irrigation
solutions, Ear drops, Nasal drops, Nasal sprays
Parenteral
(Sterile dosage forms)
Formulation
Considerations
Methods of increasing solubility
1. Co-solvency
2. pH adjustment
3. Use of surfactants/ Solubilization
4. Complexation
5. Hydrotropy
6. Chemical
modification of drug
1. Co -Solvency
• Co-solvents are used to increase solubility
E.g. of co-solvents are ethanol, sorbitol, glycerin,
propylene glycol and PEG
2. pH Adjustment
• Alteration in pH
E.g Buffer systems such as ammonium chloride,
diethanolamine, carbonic acid, phosphate buffers, glutamic acid, tartaric acid,
citric acid buffer, acetic acid buffer etc.
3. Solubilization/
Use of Surfactants
• Surface active agents
• Surfactants are used
• They have 2 portions
• Head- Polar portion
• Tail- Non- polar portion
• Polar portion is hydrophillic
• Non polar portion is hydrophobic
• When added to water at low concentrations
• Orient at the air-liquid interface
• Additional surfactant is added- the interface becomes
fully occupied
• The excess molecules are faced into the bulk of the liquid
• Higher concentrations, the surfactant molecules in the
bulk of the liquid – form oriented aggregates or micelles
• The concentration at which micelles from – Critical Micelle Concentration / CMC
• Water solubility of the solute increases with the
concentration of the micelles
E.g. Tweens, Spans, SLS etc.
To solubilize oil soluble drugs
Preparations made by this technique:
1. Cresol with soap solution
2. Solubilization of oil soluble vitamins like A, D, E and K
4. Complexation
• Solubility is increased by complexing with a complexing
agent.
• Insoluble compound + Complexing agent = Complex
• Complex has good solubility in water
Preparations made by
this technique:
Aqueous Iodine Solution: Iodine + KI = Poly iodide complex
• Polyiodide complex has good solubility in water
5. Hydrotropy
• Increase in solubility of a drug in water in the presence
of large amounts of additives
• Weak interaction between the hydrotropic agent and the solute
E.g of hydrotropic agents are sodium benzoate, urea, sodium
acetate, PVP, sodium salicylate etc.
Preparations made by
this technique:
1. Increase in solubility of caffeine by adding Sodium
Benzoate
2. Increase in solubility of theophylline by adding Sodium
Salicylate
6. Chemical
modification of the drug
• Enhances the solubility of poorly water soluble drugs
• Modifying them into their water soluble derivatives/ Salt
forms E.g. Disodium phosphate ester of betamethasone- Solubility in water is
1000 times greater than its parent compound
Formulation
1. Drug: Therapeutically active ingredient
2. Vehicles/
Solvents: Aqueous or non- aqueous
– To solubilize the ingredients
E.g. Purified water, Alcohol, Hydroalcoholic mixture,
Propylene Glycol, Glycerine, Oils
3. Viscosity
enhancers – To increase viscosity E.g. Methyl cellulose, SCMC, HPC, HPMC
4. Buffers: To
prevent change in pH E.g. Citrate buffer, Acetate buffer, Phosphate buffer
5. Stabilizers:
To protect against oxidation and microbial contamination
– Can be
Preservatives and Anti- oxidants
– Preservatives prevent
microbial contamination
E.g. Methyl paraben, Propyl paraben, Benzoic acid
– Anti-oxidants
prevent oxidation
E.g Ascorbic acid, Tocopherol, BHA, BHT
6. Organoleptic
additives- to impart taste, colour and aroma to the preparation
– Sweetening agents
– Flavouring agents
– Colouring agents
– Perfumes
ORGANOLEPTIC
ADDITIVES
• Stimulation of
sense organs
1. Tongue- Taste – Sweetening & Flavouring agents
2. Eyes- Sight – Colouring agents
3. Nose- Smell – Perfumes
1) Sweetening agents:
– Imparts sweetness E.g. Sucrose, Sorbitol,
2) Flavouring agents:
Increases palatability and easy administration
-The four basic taste sensations are salty, bitter, sweet
and sour
|
Taste |
Recommended |
|
Salty |
Butterscotch, maple, apricot, peach, vanilla, mint. |
|
Bitter |
Wild cherry, walnut, chocolate, mint combinations, anise |
|
Sweet |
Fruit and berry, vanilla |
|
Sour |
Citrus flavors, liquorice, raspberry |
3) Colouring agents:
– Enhances aesthetic appeal
– FD &C approved
colours only
– Should complement
flavour
E.g. Amaranth, Tartrazine, Erythrosine
4) Perfumes:
-Imparts an aroma to the preparation
– Used only for External preparations
E.g. Jasmine oil, Lavender oil, Ylang- Ylang, Sandalwood oil
Monophasic Liquid Dosage Form – Internal use
1. Syrups
• Syrups are sweet, viscous, concentrated, aqueous
preparations of sugar or sugar substitutes
• With or without flavoring agents and medicinal substances.
• Flavoured Syrups- contain flavoring agents
E.g. Cherry syrup, Cocoa syrup.
• Medicated syrups- contain medicinal agents
E.g. Chlorpheniramine Maleate syrup.
Formulation of Syrups
1. Drug (if it is
medicated)
2. Vehicle-
purified water
3. Sugar/ sugar
substitute
4. Flavours
5. Colours
6. Preservatives
E.g. Simple syrup, Orange syrup, Ephedrine hydrochloride
syrup
Simple
syrup I.P
• Contains 66.7% w/w sucrose.
• At this concentration the syrup:
– has high osmotic pressusre
– Self preservative
– Resistant to microbial growth
• Below 66.7 %: microbial contamination
• Above 66.7 %: crystallization
• Crystallization
• Prevention of crystallization
Preparation of Syrups
1. Simple solution – with the aid of heat or by agitation
without the use of heat. E.g. Simple /Orange syrup
2. Extraction process- E.g lemon syrup
3. Chemical reaction- E.g Ferrous Phosphate syrup
2. Elixirs
• These are clear, pleasantly flavored
• Pleasantly coloured
• Hydro-alcoholic preparations
• Potent substances like antibiotics, antihistamines, and
sedatives.
• Alcohol concentration is usually 10-40%.
• Less viscous
Formulation of
Elixirs
1. Drug
2. Vehicle –
Hydroalcoholic mixture
3. Sugar/ sugar
substitute
4. Viscosity
enhancers
5. Organoleptic
additives
6. Stabilizers
E.g. Paediatric Paracetamol elixir, Piperazine citrate
elixir
3. Linctus
• They are viscous liquid oral preparations Prescribed for
relief of dry cough.
• They contain medicaments which have demulcent, sedative or
expectorant action.
• Taken in small doses, sipped and swallowed slowly without diluting
with water
Formulation of
Linctuses
1. Drug
2. Vehicle- syrup
3. Viscosity enhancers
4. Organoleptic additives
5. Stabilizers
E.g. Simple linctus, Codeine linctus
4.
Paediatric Drops
• They are liquid dosage forms.
• For paediatric patients
• Administration –with a dropper.
• Dropper is graduated
E.g. Phenylephrine and Chlorpheniramine paediatric drops
5. Draught
• Preparations taken as a single dose
• Administered in doses of 10 ml
• Maximum volume dispensed is 50 ml in divided doses in
separate bottle)
i.e 10ml x 10ml x 10 ml x 10ml x10ml = 50 ml
E.g. Paraldeyde draught
6. Mixtures
• Aqueous preparations – Solution or suspension.
• Manufactured on a small scale
• Doses- multiples of 5 ml
• Extemporaneous preparations
• Shelf life is less
• Used for acute conditions- diarrhoea, constipation, cough,
indigestion
Monophasic Liquid Dosage Form – Used in the Mouth
1.
Mouthwashes
• Aqueous solutions
• Cleanse and deodorize the buccal cavity
• Refreshing in nature
• Concentrated or dilute form
• Maintains oral hygiene.
• They have a pleasant taste and odour.
Formulation
Antibacterial agents
Alcohol
Glycerin
Sweetening agents
Flavouring agents
Coloring agents
Containers: Clear
fluted bottles
E.g: Compound
Sodium chloride mouthwash
The label should clearly indicate the proper directions for diluting
the mouth wash before use.
Auxiliary Labelling:
“FOR EXTERNAL USE ONLY”
“NOT TO BE TAKEN”
“NOT TO BE SWALLOWED IN LARGE QUANTITIES”.
“FOR DENTAL USE ONLY”
2. Gargles
• Aqueous solutions
• Treatment of throat infections
• Relieve soreness
• Contain antiseptics/ astringents
• Diluted with warm water before use.
• Vehicle – Glycerin (viscosity, sweetness, demulcent)
• Contact time between throat and gargle is more
Formulation
Antibacterial agents/ Astringents
Astringents
Alcohol
Glycerin
Sweetening agents
Flavouring agents
Coloring agents
Containers: clear
fluted bottles / amber coloured bottles
E.g: Potassium
chlorate gargle
The label should clearly indicate the proper directions for diluting
the gargle before use
AUXILIARY LABELLING:
“FOR EXTERNAL USE ONLY”
“NOT TO BE TAKEN”
“NOT TO BE SWALLOWED IN LARGE QUANTITIES”
“FOR DENTAL USE ONLY”
3. Throat
Paints
• Viscous liquid preparations
• In the treatment of pharyngitis, laryngitis and follicular
tonsillitis.
• Vehicle is Glycerin
Formulation
1. Drug-
antiseptics, astringents and anti-infectives
2. Vehicles- Glycerin
3. Flavoring agents
4. Coloring agents
5. Sweetening agents
CONTAINER:
Colored fluted containers
E.g. Mandl’s
Paint (Compound Iodine Paint)
Direction:
Throat paints are applied on to the affected area with the help
of a brush or cotton swab and they are applied as such without dilution.
Auxiliary Labelling:
“FOR EXTERNAL USE
ONLY”
“APPLY WITH A BRUSH”
“NOT TO BE SWALLOWED IN LARGE QUANTITIES”
4. Throat
Sprays
• Aqueous or non- aqueous
• Sprayed into the throat Medication of the upper and lower
respiratory tract
E.g. Adrenaline and Atropine spray
Monophasic Liquid Dosage Form – External use
1.
Liniments
• Alcoholic or oleaginous solutions/ emulsions
• To be rubbed on the skin Rubefacient, counter irritant in
action Alcoholic liniments- better penetration
E.g. Soap liniment
Oleaginous liniments- massaging
E.g Camphor liniment
Direction:
To be applied with friction
Auxiliary Labelling:
“FOR EXTERNAL USE ONLY”
“NOT TO BE APPLIED ON CUT AND BROKEN SKIN”
“INFLAMMABLE” (If alcohol is used)
2. Lotions
• Liquid dosage forms
• External use
• Can be applied on broken skin
• Soothing in nature
• Need not be applied with friction
• Vehicle: Glycerin or Alcohol
E.g. Body lotion
Container:
Colored fluted bottles
Auxiliary Labelling:
“FOR EXTERNAL USE ONLY”
3.
Collodions
Non- aqueous liquid preparations
External application to the skin.
For small cuts and abrasions.
Vehicle is volatile – evaporates on application to skin
A flexible, protective film is left at the site of
application.
Applied with a fine brush or rod.
Two types
– Flexible and non
– Flexible collodion
Formulation
• Film forming agent – Pyroxylin (nitrocellulose)
• Solvent: Ether- alcohol.
• Flexibility imparter: Castor oil
• Adhesion- Colophony
• Water proofing- Camphor
E.g. Salicylic acid collodion
Auxiliary Labelling:
“FOR EXTERNAL USE
ONLY”
“STORE IN A COOL PLACE”
“HIGHLY INFLAMMABLE- KEEP AWAY FROM NAKED FLAME”
Monophasic Liquid Dosage Foam – Used in Body Cavities
1. Douches
• Medicated solutions
• Rinsing body cavities such as nose, vagina or urinary
bladder.
• Douches for vagina: VAGINAL DOUCHE
• For urinary bladder: IRRIGATIONS
• For nose: NASAL DOUCHE
NASAL DOUCHE
Formulation
• Drug (Antiseptic, Anti-microbial, Astringent)
• Aqueous isotonic vehicle (Purified water)
• Viscosity modifiers
• Buffers
Vaginal Douche
Irrigations
Irrigations & Vaginal douches- sterile in nature
E.g. Potassium Permanganate vaginal douche
Auxiliary Labelling
FOR VAGINAL DOUCHES:
• “FOR VAGINAL USE ONLY”
• “KEEP OUT OF REACH OF CHILDREN”
• “NOT FOR CONTRACEPTIVE USE”
• STOP USE AND ASK A DOCTOR IF RASH OR IRRITATION DEVELOPS
• DISCONTINUE USE IF ANY BURNING, ITCHING OR IRRITATION OF
THE VAGINA OCCURS DURING USE
2. Enemas
•Aqueous or oily solutions or suspensions
• Introduction into the rectum
• Cleansing, Therapeutic or diagnostic purposes
• Purgative, sedative, anthelmintic and anti-inflammatory
effects.
• X-ray examination of the lower bowel.
E.g Barium sulphate enema
Actions of Enemas
• Cleansing enemas: in constipation or before an operation
• Therapeutic enemas:
to administer Purgative, sedative, anthelmintic and anti-inflammatory
drugs
• Diagnostic enemas: X-ray examination of the lower
bowel.
E.g Barium sulphate enema
• Based on Cleansing, therapeutic and diagnostic actions,
there are 2 types:
1. Evacuation enemas
2. Retention enemas
Auxiliary Labelling:
• “FOR RECTAL USE ONLY”
• “SHAKE WELL BEFORE USE” (IF IT IS A SUSPENSION)
3. Nasal
Drops
• Are aqueous solutions
• Instilled into the nose with a dropper.
• Antiseptic, local analgesic and nasal decongestant
property
• Glass bottles with a dropper or plastic squeeze bottles
• E.g. Oxymetazoline nasal drops (Nasivion) and Otrivin.
Formulation
• Drug (Antiseptic, local analgesic and nasal decongestant)
• Aqueous isotonic vehicle (Purified water)
•Stabilizers (Preservatives)
Auxiliary Labelling:
• “FOR EXTERNAL USE ONLY” or “FOR NASAL USE ONLY”
• “KEEP OUT OF REACH OF CHILDREN”
• “CLOSE THE BOTTLE TIGHTLY AFTER USE”
• “DO NOT USE IF THE SEAL IS MISSING OR BROKEN”
4. Nasal
spray
• Are aqueous solutions
• Sprayed into the nose with a dropper.
• Antiseptic, local analgesic and nasal decongestant
property
• Plastic squeeze bottles
Auxiliary Labelling:
• “FOR EXTERNAL USE ONLY” or “FOR NASAL USE ONLY”
• “KEEP OUT OF REACH OF CHILDREN”
• “CLOSE THE BOTTLE TIGHTLY AFTER USE”
• “DO NOT USE IF THE SEAL IS MISSING OR BROKEN”
5. Ear
Drops
• Are aqueous solutions
• Instilled into ear
• Used for treating mild infections, softening wax or
cleansing after infections.
• Glass bottles with a dropper or plastic squeeze bottles
• E.g. Ciprofloxacin ear drops
Formulation
• Drug
• Vehicle- Purified water/Propylene Glycol
• Stabilizers (Preservatives)
• Viscosity Modifiers
Auxiliary Labelling:
• “FOR OTIC USE ONLY”
• “NOT FOR OPTHALMIC USE”
• “KEEP OUT OF REACH OF CHILDREN”
Summary
1. Monophasic
LDF– One phase systems/ solutions
2. Biphasic preparations – Two phase
systems
3. Monophasic LDF are classified into
– Internal use
– External use: Topical application, Used in the oral cavity,
used in body cavities
4. Methods of
increasing solubility of drugs
– Cosolvency: Use of co- solvents
– Complexation: Use of complexing agents
– Micellar solubilization: Use of Surfactants
– Hydrotropy: Use of additives
– Chemical modification of drug: using salt forms of drugs
5. Formulation of solutions
a. Drug: Therapeutically active ingredient
b. Vehicle:
Solubilize the ingredients and can be aqueous or non- aqueous
c. Viscosity enhancers: Increases viscosity
d. Buffers: Prevents change in pH
e. Stabilizers:
Anti-oxidants: Prevents oxidation
Preservatives:
Prevents microbial contamination
f. Organoleptic additives:
– Colouring agents: Enhances aesthetic appeal
– Flavouring agents: Increases palatibility
– Sweetening agents: Imparts sweetness
6. Monophasic LDF
used internally:
– Syrups: Sweet,
viscous, concentrated preparations of sugar
– Elixirs: Clear,
sweetened, flavoured, hydroalcoholic preparations
– Linctus: Sweet,
viscous preparations used for dry cough
– Pediatric drops:
Liquids for administration to children with dropper
– Draught: Single
dose preparations
– Mixtures: Small
volume, extemporaneous, preparations
7. Monophasic LDFs
used in the oral cavity:
– Gargles:
Aqueous preparations for treatment of throat infections
– Mouthwash:
Aqueous preparations for cleaning and deodorizing buccal cavity
– Throat paints:
Viscous preparations used in the treatment of throat infections and painted
inside throat
– Throat sprays:
Sprayed into throat
8. Monophasic LDFs
used externally:
– Liniments:
Applied on unbroken skin with friction
– Lotions: Can be
applied without friction on broken skin, for soothing action
– Collodions:
Non- aqueous preparations used for cuts and abrasions and which leave flexible
film on skin
9. Monophasic LDF
used in body cavities:
– Douches:
Medicated solutions used for washing body cavities like vagina & nose
– Enemas: Aqueous
or Oily solutions used in the rectum for cleansing, therapeutic or diagnostic
purposes
– Ear drops:
Aqueous solutions instilled into the ear
– Nasal drops:
Aqueous solutions instilled into the nose