Flavoring agent

Lecture 6
Prof.Shilpa.P.Chaudhari
Defination:
Flavor is a complex effect of taste, odour, and feeling factor i.e., touch, sight, and
sound, to produce physicochemical and psychological actions that influence the
perception of a substance.
Taste- primary effects of taste are sweet, sour, and salty. There is a close co-relation
ship between chemical structure and taste.
Sour taste is due to acidic nature.
Sour taste [H+] and lipid solubility of substance i.e., acids get ionized in aqueous
solution(it depends on H+ ion concentration) examples: Lemon, Vinegar, Citric acid,
Malic acid, Apple.
Salty taste is due to cationic species, halide salts. Example: Sodium chloride, sodium
bromide, sodium iodide.
Increase in molecular weight of halide results in increase in bitter taste. example:
potassium bromide, Ammonium salts.
Sodium chloride is salty, whereas , potassium chloride is bitter.
Sweet taste is due to polyhydroxy compounds.
Sweet taste [OH-] and aqueous solubility. Example: sugar, glycerin, alpha amino
acids, etc.
Odour- Odour is defined as Taste from a distance, it is very closely allied to taste.
Without odour most of substances lack in taste appeal.
Odourous volatile substances generate vapors these interact with olfactory cells and
elicit receptors and exit. The brain receives impulses from group of microscopic
olfactory receptors in the nose which it co-ordinates with the gustatory stimuli to
produce the mingled sensation that is recognized as the flavour of the substance.
Feeling factor :-feeling factor is combination of sight, sound, and touch i.e.,
texture(soft/hard) , Viscosity, coolingShilpa.P.Chaudhari
/ warmth , irritation sensation, etc. 2
Examples: flavored viscous multi-vitamin liquid gives mouthfeel effect, Menthol in
mouthwash gives cooling effect.
Purpose:

To mask unpleasant taste or odour.

To make it more palatable.

Shilpa.P.Chaudhari 3
Role in liquid dosage form:
1) In monophasic liquid(i.e., drug is in dissolved form)- it has
noticible taste, if bitter drug then for monophasic flavouring agent
with sweetening agent gives pleasant taste. Therefore, syrup retains
flavour in mouth for longer time and due to high viscosities it
decreases contact of bitter drug with taste buds and give mouthfeel
effect.
If drug is bitter and want to prepare without flavoring agent then use
glycerin as a vehicle-sweet, highly viscous it may act as a barrier
between drug molecule and taste buds.
Biphasic Liquid- a) soluble drug in form of emulsion
b) Insoluble drug in form of suspension
Entrapment of bitter drug in emulsion increases palatability and
insoluble drug in form of suspension is more palatable then solution
as less reaction with taste buds.
Disadvantages: If flavouring agent added to biphasic suspension
with finely divided particle then more chance to adsorp flavour on
particle therefore no flavour present to impart taste. In
emulsion(O/W) flavour oil may get entrap in the micellar structure
form by surfactant and is notShilpa.P.Chaudhari
free to impart taste. 4
 Role in Solid dosage form:
Solids remain for short time. They quickly pass
through mouth. So less contact time between taste
buds. Therefore flavouring is not important.
Even in capsule no need of flavouring agent
because the taste is masked by gelatin.
But in case of disperse tablet, Kids tablet, Chewable
tablet, Lozenges it is very essential to add flavoring
agent because it is in contact with taste buds for a
longer time.
Role in semi-solid dosage form:
For external use flavoring not required but for
internal use flavoring is required.
Shilpa.P.Chaudhari 5
 Selection of Flavor:
Selection or creation of an acceptable flavour is more of an art than science. Selection is
a feel i.e combined effect of touch, sight, and sound, it should be compatible and non-toxic
rather than a measure or physicochemical selection it is a psychological selection. The
most useful background for section is practical experience, but, even with the wealth of
this, much trial and error may be unavoidable.
There are various factors taken into consideration during the selection of flavours:
Unique flavoring problems:
Suitable assessment and consumer acceptance.( volunteers are hard to find, only a
few samples samples should be examined at each session because repeated tasting
numbs the taste buds and so raises the taste threshold, the full dose of the preparation
must be taken and the experiment should be designed to minimize the effects of
personal variation and other factors such as temperature, age , environment and time
of the day.)
Depending on physicochemical properties of dosage forms: State(solid or liquid),
Viscosity( more viscous more palatable), vehicle and water content( to determine
solubility of flavor), temperature, storage condition(deterioration of flavors may be
accelerated by alkaline pH as in cinnamon oil , hydrolysis and oxidation of flavors while
loss may occur through volatilization from an imperfectly fitting closure or by
adsorption into certain plastics. The preparation should be subjected to an accelerated
storage test to show that none of these problems exists.) Incompatibility(tests should
be performed on the complete preparation because other ingredients, such as
antimicrobial preservatives ,may modify the taste.)
Whether an allergic reactions, idiosyncrasies, or toxicity reported for flavor or it is
better to write name of flavoring agent on the label.
Route of administration- determines toxicity and safety of flavor( if parentral route no
need of flavouring agent )
Response may not be same in healthy and disease state- while a flavor that is
acceptable for a short time may become objectionable if treatment is prolonged.
Shilpa.P.Chaudhari 6
Sweetening agents that rise blood sugar or increase calorie intake cannot be included in
formulations for diabetics or patients on restricted diets.
 Selection depends on age of the patient:
Adult prefers sour taste ,childrens like fruit flavor- peppermint, orange, lemon, pineapple .
3)Depending on the taste of objectionable medicament
Taste Suitable Flavor
Salty Vanilla, Butterscotch, orange, apricot, mint, raspberry
Bitter Chocolate,lemon, cherry, anise.
Sweet Vanilla
Sour Citrus, liquorice, raspberry
Blends of flavor can also be used: Blending of taste is generally more effective than adding a
large excess of a powerful but unrelated flavor. Examples: Sour taste can be blended with salty
taste. Salt reduces sourness and increases sweetness. Bitter drugs can be blended with citrus
and mint flavors, butterscotch and caramel flavors with salty drugs.
Association between category, flavor and color:
For antacids usually reddish shades are preferred gelusil (erythromycin dye)
Digene(Amaranth) and Mint flavor.
Red stimulates digestive system, blood circulation and arouses force of self preservation.
Mint - carminative and digestive effect.
All tonics are usually reddish for psychological effect.
Over shadow effect: Intensity of flavor is stronger and longer. Bitterness is the hardest basic taste
to cover. Some bitter medicaments leave a persistent and unpleasant after taste which
occasionally can be overcome by a lingering flavor such as chocolate or apricot,
By including adjuvants, such as glycine and monosodium glutamate, that has been found to
reduce the bitter effect.
In cough syrup liquorice extract mask the unpleasant taste of medicament, In O/W emulsion
Masking unpleasant taste of oil by water.
Carbon dioxide produces effervescence and gives saline taste to unpleasant tasting drug in
effervescent powders.
Desensitization: Menthol, and peppermint oil appears to have a mild local anesthetic action on
the taste buds.
Physical modification in dosage form: Use of virtually insoluble and therefore tasteless derivative
Shilpa.P.Chaudhari 7
of a drug; e.g., chloramphenicol cinnamate or palmitate instead of the very bitter parent antibiotic,
or increase in viscosity of dosage form also reduce contact time and make it palatable.
 Products and there preferred
flavors:

Cough syrup- anise , raspberry, mint, liquorice.

Liver preparation- Apricot, raspberry, Stawberry.
Protien hydrolysate- Honey, butterscotch, pineapple,
banana.
Antacid-Mint menthol, ginger
VitaminA- Caramel, butterscotch, orange
Laxative- Vanilla, Strawberry
Papain pepsin- cardamom, pineapple

Shilpa.P.Chaudhari 8
Types of flavoring agents:

1) Natural Flavoring agents

2) Artificial flavoring agents
Flavors are combined with the sweetening
agents like sucrose, sorbitol, invert syrup,
saccharine, etc. to enhance the flavoring
effect.

Shilpa.P.Chaudhari 9
 Natural flavors:
Volatile oils such as anise, caraway, cinnamon, clove, dill, ginger, lemon, orange
and peppermint are used as flavoring agents in a variety of forms.The vehicles of
mixtures are often aromatic waters while alcoholic or hydroalcoholic solutions of
oils(tinctures or, more often, spirits) provide convenient concentrated
preparations for flavoring purposes (lemon, peppermint and compound orange
spirits, and strong ginger tincture are examples)
Flavors containing aromatic oils(except lemon and orange) are more suitable
than fruit syrups for neutral preparations. Fruit flavors are prepared from fruit
juices, peel of citrus fruits. Lemon and orange oils keep badly and develop an
unpleasant turpentine-like taste. By removing most of the terpenes, terpeneless
oils are produced which, compared with the natural oils, are about 20 times
stronger in flavor and odour, are more readily soluble and have better stability.
For solid dosage form- vanillin crystals,dried lemon extract
For liquid dosage form- Alcoholic , aqueous, hydroalcoholic (tinctures and spirits
are used.
Limitations of natural flavors:
These are chemically and microbiologically unstable.
Extracts vary in nature or composition.
Removal of water, resinous material, terpenes and sesquiterpenes improves stability of
flavors.(fractional distillation required)

Shilpa.P.Chaudhari 10
 Synthetic flavors:
These are prepared by chemical reactions. Inaddition to synthetic
sweeteners other synthetic chemicals are used in flavoring. These are
often preferred to natural materials because of their more constant
composition, More ready availability,lower cost, greater stability, and
more predictable incompabilities.
Examples: Ester (methylsalicylate), Aldehydes( Synthetic vanillin,
benzaldehyde, cinnamaldehyde) fatty alcohols, ketones , lactones and
alcohols are used. Chloroform has an agreeable, warm, sweet taste
and used as a vehicle Chloroform water BP.
For emulsified products, Soft flavors like benzaldehyde and vanillin are
most suitable. Benzaldehyde has the odour of bitter almonds and is a
substitute for wild cherry syrup and volatile bitter almond oil. Vanillin is
useful when, as with liquid paraffin emulsions , the medicament has
bland taste. Fractionated coconut oil, a non-aqueous vehicle for oral
preparations, is difficult to flavor because of its oily nature; imitation
ground almond oil and olive oil are suitable flavors.
Exact duplication of natural flavor is impossible because it is not
possible to detect and prepare all components which are present in
natural flavor and hence it is blended with natural flavors.

Shilpa.P.Chaudhari 11
References
James Swarbrick; Encyclopedia of Pharmaceutical Technology 3rd edition;vol-
1; 648-670,.
James Swarbrick; Encyclopedia of Pharmaceutical Technology 3rd edition;vol-
3; 1609-1662, 17631772.
Ashok Katdare; Mahesh V. Chaubal; Excipient Development for
pharmaceutical Bitechnology and drug delivery systemsInforma Healthcare
London; 1-14,37-49.
http://www.aapspharmscitech.org/view.asp?art=pt060241
Internation Pharmaceutical Excipent council USP 7th Annual Meeting
Hyderabad 7th February 2008; Excipient Funtionality, specifications and
Monographs PPT by S.D.Joag Hon Gen Secretary IPA
Director,Dr.M.K.Rangnekar Lab,Mumbai.
Training Workshop on Pharmaceutical Development with focus on Paediatric
Formulations pharmaceutica Product development;Tallink City Hotel Tallinn,
Estonia
Date: 15 - 19 October 2007; organized by World Health Organization.
Cooper and Gunns; Dispensing for Pharmaceutical Students; 12th edition; CBS
publisher and distributers, New Delhi; 47-53.

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