Flavouring Agents.
Martindale�s 24th.
Compiled and Edited by Ivor Hughes.

Use of Flavouring in Medicines. Preparations for oral administration are often flavoured in order to make them acceptable to patients. Highly flavoured media may be required to mask the obnoxious taste of certain drugs, which may be refused or cause nausea and vomiting, particularly on repeated dosage. On the other hand, attention has been drawn to the dangers of pleasantly flavoured preparations of potent drugs.

The principal flavouring agents used are aromatic oils  and waters, chloroform, sweetening agents, liquorice, cocoa, various syrups prepared from fruit or from the peel of citrus fruits, vanilla, vanillin and imitation flavourings. In addition to flavouring, some of these preparations have other properties, for example, aromatic waters are also carminative and chloroform water is also a preservative. Many flavouring agents, on dilution, form media suitable for microbial growth and it is therefore necessary to add suitable preservatives.

Flavours Suitable for Masking Unpleasant Tastes. The most acceptable flavour in a given case depends largely on the preference of the individual patient, but a flavour which is usually associated with the type of taste to be covered may be useful, for example, orange or gentian used with bitter alkaloids, and fruit flavours to cover the sour taste of hydrochloric acid. Substances such as menthol or peppermint oil which produce mild local anaesthesia may help to disguise a variety of tastes. Salty substances are best given in flavoured syrups, such as syrup of raspberry. The saltiness tends to bring out the flavour of the syrup; the addition of a little sodium chloride may make some preparations more palatable. Mucilages and syrups make some tastes less objectionable. When a mixture is to be administered over a long period, it is advisable to vary the flavour from time to time.

The following flavourings have been recommended.
For Bitter Drugs
(e.g. quinine and other alkaloids). Liquorice, syrups of orange and lemon, aromatic eriodictyon, bilberry, cacao and raspberry syrups, and imitation coconut, raspberry, sarsaparilla or wild cherry syrups; citric acid should be added to the imitation raspberry flavouring, and may be an advantage with the imitation wild cherry.

For Saline Substances. Liquorice, syrups of orange and lemon, other fruit syrups, carbon dioxide water and effervescent preparations.
Cinnamon oil with syrup may be useful for sodium salicylate, iron and ammonium citrate, and ammonium chloride.

For Bitter, Metallic or Fishy Tastes. 0.05 to 0.1% of monosodium glutamate makes the flavour less objectionable.�J. F. Caul and E. L. Rockwood, . Amer. pharm. Ass., Sci. Edn, 1953, 42, 682.

For Antibiotics (aureomycin, oxytetracycline, penicillin). Cacao syrup and imitation butterscotch, cream soda, ginger ale, raspberry, root beer and wild cherry syrups.�B. L. McLaughlin and C. H. Becker, J. Amer. pharm. Ass., Sci. Edn, 1955, 44, 120.

For comparative tests on flavouring agents for masking tastes see B. L. Lankford and C. H. Becker, /. Amer. pharm. Ass., Sci. Edn, 1951, 40, 77 and 83.

Formulae for cherry vehicle (sugarless), coffee syrup, lemon syrup, sarsaparilla syrup, tea syrup (for iced tea), vanilla extract and artificial grape and walnut flavours are given in 'Remington's Practice of Pharmacy', 11th Edn 1956 (E. W. Martin and E. Fullerton Cook, Ed.), Mack Publishing Co., Easton, Pa., pp. 1178.

Formulae for imitation butterscotch, coconut, cream soda, grape, maple, raspberry, root beer and wild cherry concentrates are given by B. L. Lankford and C. H. Becker, /. Amer. pharm. Ass., Sci. Edn, 1951, 40, 77. A formula for imitation ginger ale concentrate is given by B. L. McLaughlin and C. H. Becker, J. Amer. pharm. Ass., Sci. Edn, 1955, 44,114.

For imitation sarsaparilla flavour, see under Sassafras Oil.

Raspberry. Rubus Idaeus; Framboise (Fr. P.); Himbeer. 
The fresh ripe fruit of Rubus idaeus (Rosaceae). Included in Fr. P., Jug. P., Pol. P., and Swiss P.
Uses. It is used as a colouring and flavouring agent.

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Raspberry Juice (U.S.P.). Succus Rubi Idaei. 
The juice expressed from the fresh ripe fruit of varieties of R. idaeus or of the native American species .R. strigosus (Rosaceae). It contains not less than 1.5% of acids calculated as citric acid.

Raspberry Syrup (U.S.P.). 
Raspberry juice 47.5 ml., sucrose 80 g., alcohol 2 ml., water to 100 ml. Protect from light.

Syrup of Raspberry (B.P.C.). Syr. Rubi Idaei; Sirop de Framboise (Fr. P.). 
Clarified juice of fresh raspberries 500 ml. or concentrated raspberry juice of commerce suitably diluted, and sucrose 800 g. It may be preserved with sulphurous acid or sodium metabisulphite to produce a final content of not more than 350 p.p.m. w/w of SO2. Wt per ml. 1 .30 to 1 .32 g. Store in a cool place.

The clarified juice of fresh raspberries used for the preparation of this syrup is obtained by pulping a sufficient quantity of raspberries, adding enough pectinase to destroy the pectin, allowing to stand for 12 hours, pressing and clarifying the juice. Pol. P. and Swiss P. include a raspberry syrup prepared from fermented raspberry juice.

S.P.P. (Syrup pro Penicillin) (Medo-Chemicals). A sterilised buffered raspberry syrup. It is used for the preparation of a stable syrup containing penicillin 50,000 units, 100,000 units, or 200,000 units per 60 minims.

Red Cherry. Cerasus; Cerise Rouge (Fr. P.); Griotte (Fr. P.). 
The fresh ripe fruit of varieties of the red or sour cherry, Prunus cerasus (Rosaceae).
Uses. It is used as a colouring and flavouring agent.

Cerise Noire (Fr. P.) (Guigne or Cerise Douce) is the gean or wild cherry, Prunus avium.

Cherry Juice (U.S.P.). Succus Cerasi. The juice expressed from the fresh ripe fruit of P. cerasus, and containing not less than 1 % of malic acid.

Cherry Syrup (U.S.P.). Cherry juice 47.5 ml., sucrose 80 g., alcohol 2 ml., water to 100ml.

Syr. Ceras. (B.P.C. 1934). Syrup of Cherry. The expressed juice of red cherry 400 g. and sucrose 600 g. Dissolve with the aid of heat, cool, replace the water lost by evaporation, and strain. 
Dose: 2 to 4 ml. (30 to 60 minims).

Red Currant. Ribes Rubrum; Groseille (Fr, P.). The fresh ripe fruit of Ribes rubrum.
Uses, It is used as a colouring and flavouring agent.

Syr. Rib. Rub. (B.P.C. 1934). Syrup of Red Currant. 
Press a sufficient quantity of a mixture of red currant 100 and red cherry 15 to yield 400 g. of juice; add sucrose 600 g., heat until dissolved, cool, replace the water lost by evaporation, and strain. 
Dose: 2 to 4 ml. (30 to 60 minims).

Sarsaparilla (B.P.C. 1949). Sarsa; Sarsaparilla Root; Salsepareille.
Foreign Pharmacopoeias: In Selg., Chil., Fr., Ger., Nor., and Swiss. Also in U.S.N.F.
The dried root of various species of Smilax (Liliaceae). It is almost odourless and has a mucilaginous, somewhat sweetish and acrid taste.
Uses. It was formerly used in chronic rheumatism and skin affections but has no therapeutic value. It is chiefly used as a vehicle for medicaments.

Compound Sarsaparilla Syrup (U.S.N.F.). 
Sarsaparilla fluidextract 200 ml., glycyrrhiza fluidextract 15 ml., oils of sassafras and anise of each 0.2 ml., methyl salicylate 0.2 ml., alcohol 19.4 ml., and syrup 765 ml. A suitable vehicle for bitter alkaloidal salts and drugs with a salty taste. Most acceptable to children.

Dec. Sars. Co. (B.P.C. 1949). Compound Decoction of Sarsaparilla. 
Macerate Sarsaparilla 12.5 g., guaiacum wood 1.25 g., and liquorice 1.25 g. for one hour with 150 ml. of water, then boil for 10 minutes, cool, add sassafras oil 0.006 ml., strain, and, if necessary, pour sufficient water over the strainer to produce 100 ml. 
Dose: 60 to 240 ml. (2 to 8 fl. oz.).

When Compound Decoction of Sarsaparilla is prescribed, either the above or the concentrated decoction diluted with 7 times its vol. of water may be dispensed.

Dec. Sars. Co. Cone. (B.P.C. 1949). Concentrated Compound Decoction of Sarsaparilla. 
Infuse at 70� for one hour Sarsaparilla 100 g, with water 500 ml. at 70�; repeat the infusion twice with similar quantities of water. Exhaust by boiling with water, guaiacum wood 10 g. and liquorice 10 g. Mix the 3 infusions with the decoction and rapidly evaporate to 75 ml.; add sassafras oil 0.05 ml. dissolved in alcohol (90%) 22.5 ml., set aside for 14 days, filter, and pour sufficient water over the filter to produce 100 ml. 
Dose: 8 to 30 ml. ( � to 1 fl oz.).

Sarsaparilla Fluidextract (U.S.N.F.). An alcoholic percolate of Sarsaparilla 1 in 1

Vanilla (B.P.C. 1934). Vanilla Beans; Vanilla Pods.
Foreign Pharmacopoeias: In Belg., Fr., Mex., Swiss, and U.S.
The cured, fully grown, unripe fruit of Madagascar, Mexican, or Bourbon vanilla, Vanilla planifolia, or of Tahiti vanilla, V. tahitensis (Orchidaceae). It usually contains about 2 to 3% of vanillin. Its odour and flavour is not entirely due to vanillin but depends on the presence of other aromatic substances. Tahiti vanilla contains a lower percentage of vanillin and has an odour slightly different from the other varieties. Store in a cool place; vanilla which has become brittle should not be used.
Uses. It is used as a flavouring agent and in perfumery.

Vanilla Tincture (U.S.P.). Tintura de Vainilla (Mex. P.)
1 in 10, prepared by maceration and percolation with diluted alcohol and containing 20% w/v of sucrose.

Vanillin (B.P.). Vanillic Aldehyde. 4-Hydroxy-3-methoxybenzaldehyde.
Foreign Pharmacopoeias: In Belg., Chil., Cz., Dan., Egyp., Ger., Hung., Ind., Jug., Mex., Span., Swed., Swiss, and U.S.
White or cream-coloured, crystalline needles or powder with an odour and taste of vanilla. It can be extracted from vanilla, but is usually prepared synthetically from eugenol or guaiacol. M.p. 81� to 83�. Solutions in water are acid to litmus.
Soluble 1 in 100 of water; more soluble in boiling water; soluble 1 in 20 of glycerin and in solutions of alkali hydroxides; freely soluble in alcohol, chloroform, ether, and fixed and volatile oils. Incompatible with oxidising agents and ferric salts. Protect from light.
Uses. It is used as a flavouring agent and in perfumery.

Vanillin 1 g., benzaldehyde 0.3 ml., oil of fennel 0.6 ml., chloroform 0.6 ml., glycerin 50 ml., orange flower water 200 ml., saccharin sodium 750 mg., water to 1000 ml. Shake with talc or other suitable material, and filter.� H. D. Fifer and S. J. Dean, /. Amer. pharm. Ass., Pract. Pharm. Edn, 1953, 14, 771.

Ethyl Vanillin (U.S.N.F.). 3-Ethoxy-4-hydroxybenzaldehyde.
Fine white or slightly yellowish crystals with a vanilla-like odour and taste. M.p. 76� to 78�. Solutions in water are acid to litmus.
Soluble 1 in 100 of water at 50�; freely soluble in alcohol, chloroform, ether, and solutions of alkali hydroxides. Protect from light.
Uses. As for Vanillin but it has a finer and more intense odour.

Coumarin (U.S.N.F., B.P.C. 1934). Coumar.; Cumarin; Tonka Bean Camphor. 
The lactone of cis-o-coumarinic acid. C9H6O2 = 146-1.
Coumarin is the odorous principle of Tonka seed (Tonka or Tonquin bean); it may be prepared synthetically. It occurs as colourless prismatic crystals with a characteristic persistent fragrant odour and a bitter aromatic burning taste. M.p. 68� to 70�.
Soluble 1 in 500 of water and 1 in 50 of boiling water; soluble in most organic solvents and in solutions of alkali hydroxides.
Uses. It is used as a flavouring agent and as a fixative in perfumery. One part of coumarin is approximately equivalent in flavour to 3 parts of vanillin.