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, cooling / warmth , irritation sensation, etc. Shilpa.P.Chaudhari 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

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 not free to impart taste. Shilpa.P.Chaudhari 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.
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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. Shilpa.P.Chaudhari Physical modification in dosage form: Use of virtually insoluble and therefore tasteless derivative 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

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

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)

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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.

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References

James Swarbrick; Encyclopedia of Pharmaceutical Technology 3rd edition;vol1; 648-670,. James Swarbrick; Encyclopedia of Pharmaceutical Technology 3rd edition;vol3; 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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