Organoleptive additives- colours, flavors and sweeteners-sources, mechanism/basic principles and examples

1. Organoleptive
additives
A. Colours,
B. Flavours
C. Sweeteners

2. A. Coloring agents

3. Purpose
• Coloring agents are used mainly to impart a distinctive appearance to
a pharmaceutical dosage form.
• The main categories of dosage form that are colored are:
• Tablets: either the core itself or the coating.
• Hard or soft gelatin capsules: the capsule shell or coated beads.
• Oral liquids.
• Topical creams and ointments.

4. Need & Use
• Color is a useful tool to help identify a product in its manufacturing and
distribution stages.
• Patients, especially those using multiple products, often rely on color to be
able to recognize the prescribed medication.
• The use of different colors for different strengths of the same drug can also
help eliminate errors
• Unattractive medication can be made more acceptable to the patient by the
use of color
• Providing useful opacity, which can contribute to the stability of light-sensitive
active materials in the tablet or capsule formulation. E.g. Pigments such as the
iron oxides, titanium dioxide are especially useful for this purpose

5. Types of coloring agents
• Dyes: soluble in water
• Pigments: insoluble in water
• Stability vs safety
• Inorganic pigments, show excellent stability than other coloring agents,
• Organic colors, have poor stability properties but are used in formulations
because of their low toxicity

6. Coloration /Surface coloration (Tablets)
• For surface coloration of tablets, the choice of color is usually
restricted to insoluble pigments. The reasons for this include their
lack of color migration, greater opacity, and enhanced color stability
over water-soluble colors
• Lakes are largely water-insoluble forms of the common synthetic
water-soluble dyes. Lakes should be stored in well-closed, light-
resistant containers at a temperature below 30°C
• Mottling: It is unequal distribution of color on the tablet, with light
or dark spots standing out on uniform surface

7. Safety
• Toxicology studies are routinely conducted on an ongoing basis by
organizations such as
• World Health Organization (WHO)
• US Food and Drug Administration (FDA),
• European Commission (EC).
• Various regulatory bodies around the world have developed lists of
permitted colors that are generally regarded as being free from
serious adverse toxicological effects

8. Certification
• Colors requiring certification are described as-
• FD&C (Food Drug and Cosmetic);
• D&C (Drug and Cosmetic) or External D&C.
• The remaining colors are described as uncertified colors and are
mainly of natural origin

9. Examples
Permanently listed color additives
subject to US certification
Provisionally listed color additives
subject to US certification

10. Titanium Dioxide
• White, amorphous, odorless, and tasteless non hygroscopic powder.
• Although the average particle size of titanium dioxide powder is less
than 1 mm, commercial titanium dioxide generally occurs as
aggregated particles of approximately 100 mm diameter.
• Anatase is the form most commonly used in pharmaceutical
applications

11. Titanium Dioxide
• Functional Category: Coating agent; opacifier; pigment
• Titanium dioxide is widely used in confectionery, cosmetics, and
foods, in the plastics industry, and in topical and oral pharmaceutical
formulations as a white pigment.
• Owing to its high refractive index, titanium dioxide has light
scattering properties that may be exploited in its use as a white
pigment and opacifier

12. Titanium Dioxide
• Method of Manufacture
• Titanium dioxide occurs naturally as the minerals rutile (tetragonal
structure), anatase (tetragonal structure), and brookite
(orthorhombic structure).
• Titanium dioxide may be prepared commercially by either the sulfate
or chloride process. In the sulfate process a titanium containing ore,
such as ilemenite, is digested in sulfuric acid.
• This step is followed by dissolving the sulfates in water, then
precipitating the hydrous titanium dioxide using hydrolysis.
• Finally, the product is calcinated at high temperature.

13. Titanium Dioxide
• Safety
• Titanium dioxide is widely used in foods and oral and topical
pharmaceutical formulations.
• It is generally regarded as an essentially nonirritant and nontoxic
excipient

14. Flavouring Agent
https://www.ncbi.nlm.ni
h.gov/pmc/articles/PMC
3331350/pdf/ASL-8-
38.pdf

15. Purpose
• Mask (hide) the unpleasant taste sensation of API by use of blends of
distinctive flavors.
• The specific therapeutic agents are associated with specific flavors in
certain formulations.
• E.g. an orange-mint flavor is especially used in diphenhydramine
expectorant formulation

16. Types
• Salty: Butterscotch, vanilla
• Bitter: Walnut, Chocolate, Mint
• Sweet: Berry, Mango
• Sour: Orange, Raspberry

17. Preferred flavour

18. Vanillin
• Chemical Name: 4-Hydroxy-3-methoxybenzaldehyde
• Description: White or cream, crystalline needles or powder with
characteristic vanilla odor and sweet taste
• Functional Category: Flavoring agent.
• Applications in Pharmaceutical Formulation: Vanillin is widely used as
a flavor in pharmaceuticals, foods, beverages, and confectionery
products, to which it imparts a characteristic taste and odor of natural
vanilla

19. Vanillin
• Method of Manufacture
• Vanillin occurs naturally in many essential oils and particularly in the
pods of Vanilla planifolia.
• Industrially, vanillin is prepared from lignin, which is obtained from
the sulfite wastes produced during paper manufacture.
• Lignin is treated with alkali at elevated temperature and pressure, in
the presence of a catalyst, to form a complex mixture of products
from which vanillin is isolated.
• Vanillin is then purified by successive recrystallizations.

20. Vanillin
• Safety
• There have been few reports of adverse reactions to vanillin
• Adverse reactions that have been reported include contact dermatitis
and bronchospasm caused by hypersensitivity.
• LD50 (mouse, IP): 0.48 g/kg
• Regulatory Status: GRAS listed.

21. Sweetening Agents

22. Purpose/Need/Use
• To increase the palatability of the dosage form and mask unpleasant
taste of API in formulation
• The main sweetening agents employed in oral preparations are
sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium and
aspartame
• Generally used in solid oral and liquid oral formulations
• Used in formulations: Chewable tablets, Oral suspension, Oral
solutions
• E.g. Sucrose solution (syrup), Saccharin

23. Saccharin Sodium
• Functional Category: Sweetening agent
• Applications in Pharmaceutical Formulation : Saccharin sodium is an
intense sweetening agent used in beverages, food products, table-top
sweeteners, and pharmaceutical formulations such as tablets,
powders, medicated confectionery, gels, suspensions, liquids, and
mouthwashes
• It is also used in vitamin preparations.
• Saccharin sodium is considerably more soluble in water than saccharin,
and is more frequently used in pharmaceutical formulations.
• Its sweetening power is approximately 300–600 times that of sucrose.
• Saccharin sodium enhances flavor and mask some unpleasant taste
characteristics.

24. Saccharin Sodium
• Method of Manufacture
• Saccharin is produced by the oxidation of o-toluene sulfonamide by
potassium permanganate in a solution of sodium hydroxide.
• Acidification of the solution precipitates saccharin, which is then
dissolved in water at 50°C and neutralized by addition of sodium
hydroxide.
• Rapid cooling of the solution initiates crystallization of saccharin
sodium from the liquors.

25. Saccharin Sodium
• Safety
• The WHO has set a temporary acceptable daily intake of up to 2.5
mg/kg body-weight for saccharin, including its salts
• Regulatory Status: GRAS, Accepted for use as a food additive in
Europe