Pharmaceutical excipients

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					Information of some Coloring Agents
(Iron Oxides, Beta Carotene, Indigo, Sunset Yellow, Titanium oxides)

Submitted to:

Md. Saiful Islam
Assistant professor Department of pharmacy The University of Asia Pacific

Submitted by:

Md. Reazul Islam Reg.#08103044
Department of Pharmacy The university of Asia Pacific

(2nd year 2nd semester)

Submission Date:

Some definitions

The word ‘Pigment’ is derived from the Latin word pigmentum- pingere, to paint. A pigment is a material that changes the color of reflected or transmitted light as the result of wavelengthselective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light. Many materials selectively absorb certain wavelengths of light. Materials that humans have chosen and developed for use as pigments usually have special properties that make them ideal for coloring other materials. A pigment must have a high tinting strength relative to the materials it colors. It must be stable in solid form at ambient temperatures.

A dye can generally be described as a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and may require a mordant to improve the fastness of the dye on the fiber. There are many types of dyes, such as Organic dyes       Acid dyes Basic dyes Mordant dyes Vat dyes Disperse dyes Sulfur dyes

 Food dyes


Some of the insoluble colors or pigments have the additional benefit when used in tablet coatings or gelatin shells of providing useful opacity, which can contribute to the stability of lightsensitive active materials in the tablet or capsule formulation; lakes are especially useful for this purpose. lakes are of low hazard and standard chemical handling precautions should be observed depending upon the circumstances and quantity of material handled. Special care should be taken to prevent excessive dust generation and inhalation of dust.
e.g. Crimson Lake, Madder Lake.

Sunset Yellow (FD & C Yellow no-6):
Synonyms: E110; FD&C yellow #6; 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic
acid disodium salt; 1-psulfophenylazo-2-naphthol-6-sulfonic acid disodium salt; yellow orange S.[3]

Empirical formula: C16H10N2O7S2 .2Na[3] Molecular weight: 452.37 [3] Structure:

Physical Properties:
Appearance: Reddish yellow powder. Aqueous solutions are bright orange colored.


Melting Point: 390 C (decomposes)[3] Solubility:

Name of the Solvent Acetone

Solubility at 200C unless otherwise stated 1 in 38.5

Ethanol (75%)

1 in 333


1 in 5

Propylene glycol

1 in 45.5

Propylene glycol (50%)

1 in 5


1 in 5.3 at 28C


1 in 5.3 at 258C


1 in 5 at 608C


Poorly compatible with citric acid, saccharose solutions, and saturated sodium bicarbonate solutions. Incompatible with ascorbic acid, gelatin, and glucose. [3]

 Incompatible with strong oxidizing agents;  Light stability is very good;  Heat stability is also good.[3]

Specific Purpose:
 It may be added to foods to induce a color change;

 It is a synthetic coal tar and azo yellow dye useful in fermented foods which must be heat treated.  It can be found in sweets, hot chocolate mix and packet soups, trifle mix, breadcrumbs and cheese sauce mix and soft drinks, fortune cookies, some red sauces, certain pound cakes, snack chips and other yellow, orange, and red food products.  Specifically it can be found in the capsules of DayQuil (in high concentrations).  Sunset Yellow is often used in conjunction with E123, Amaranth, in order to produce a brown colouring in both chocolates and caramel.[3]

Indigo Carmine (FD & C Blue no 2):
2-(1,3-Dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-1H-indole-5-sulfonic acid disodium salt; disodium 5,50-indigotin disulfonate; E132; FD&C blue #2; indigotine; sodium indigotin disulfonate; soluble indigo blue.[3]

Chemistry of Indigo (FD & C Blue No.2)
Empirical formula: C16H8N2Na2O8 S2 Molecular weight: 466.37 Structure:

Physical Properties:
Appearance: Dark blue powder. Aqueous solutions are blue or bluish-purple.


Melting point: 390–392 °C

Solvent Acetone Ethanol (75%) Glycerin Propylene glycol Propylene glycol (50%) Water Water water

Solubility at 20 C unless otherwise stated Practically insoluble 1 in 1430 1 in 100 1 in 1000 1 in 167 1 in 125 at 2 c 1 in 25 c 1 in 45 at 60 c

Poorly compatible with citric acid, saccharose solutions, and saturated sodium bicarbonate solutions. Incompatible with ascorbic acid, gelatin, and glucose.

 Sensitive to light  The instability was more pronounced at higher pH and in the absence of a photo stabilizer

Specific Purpose:
 Indigo carmine is an indigoid dye used to color oral and topical pharmaceutical preparations.  It is used with yellowcolors to produce green colors.  Indigo carmine is also used tocolor nylon surgical sutures and is used diagnostically as a 0.8% w/v injection. [3]  It is used in desert powders, bakery goods, cereals, ice cream, sherbet, and dairy products. [5]

Beta-carotene is one of a group of natural chemicals known as carotenes or carotenoids.[3] Beta carotene is converted in the body to vitamin A. It is an antioxidant, like vitamins E and C. Carotenes are responsible for the orange color of many fruits and vegetables such as carrots, pumpkins, and sweet potatoes.[3][1]

Synonyms: Betacarotene; b-carotene; b,b-carotene; E160a.

Chemistry: 
Empirical formula: C40H56

 Molecular weight: 536.85  Structure:

Physical Properties:
 Appearance: Occurs in the pure state as red crystals when recrystallized from light petroleum.[3]

 Melting point: 1830C  Solubility:   Soluble 1 in 30 parts of chloroform; Practically insoluble in ethanol, glycerin, and water;[3]

Generally incompatible with oxidizing agents; decolonization will take place.[3]

 Beta-carotene is very susceptible to oxidation and antioxidants such as ascorbic acid, sodium ascorbate, or tocopherols should be added. Store protected from light at a low temperature (–2080C) in containers sealed under nitrogen.[3]

Conditions of Instability:
 Beta-carotene is particularly unstable when used in spray-coating processes, probably owing to atmospheric oxygen attacking the finely dispersed spray droplets.  Betacarotene is very unstable to light and air, and products containing this material should be securely packaged to minimize degradation.  Because of its poor water solubility, beta-carotene cannot be used to color clear aqueous systems, and cosolvents such as ethanol must be used. [3]

Specific Purpose:
 Beta-carotene is capable of producing colors varying from pale yellow to dark orange. It can be used as a color for sugarcoated tablets prepared by the ladle process.  Beta carotene is used in foods to provide color  Beta carotene is sometimes added to products for its antioxidant effects, to keep fats from going rancid.  The body turns it into vitamin A, and beta carotene is sometimes added to foods or vitamin supplement as a nutrient.

 Suppositories have been successfully colored with beta-carotene in approximately 0.1%

Iron Oxides:
Iron oxides are defined as inorganic compounds consisting of any one of or combinations of synthetically prepared iron oxides,including the hydrated forms.

(a) Iron oxide black: Bayferrox 306; black magnetic oxide; black oxide, precipitated; black rouge; CI 77499; E172; ethiops iron; ferric ferrous oxide; ferrosoferric oxide; Ferroxide 78P; Ferroxide 88P; iron oxide; iron (II, III) oxide; iron oxides (FeO); magnetite; Mapico Black EC; pigment black 11; Sicovit B80; Sicovit B85; triiron tetraoxide. (b) Iron oxide red: anhydrous ferric oxide; anhydrous iron (III) oxide; Bayferrox 105M; CI 77491; diiron trioxide; E172; Ferroxide 212P; Ferroxide 226P; hematite; pigment red 101; red ferric oxide; Sicovit R30. (c) Iron oxide yellow monohydrate: E172; hydrated ferric oxide; iron (III) oxide monohydrate, yellow; pigment yellow 42; yellow ferric oxide. Iron (III) oxide hydrated: Bayferrox 920Z; CI 77492; ferric hydroxide; ferric hydroxide oxide; ferric hydrate; ferric oxide hydrated; Ferroxide 510P; iron hydrate; iron hydroxide; iron hydroxide oxide; Mapico.

 Empirical Formula:

Chemical name Yellow iron oxide Colcothar (red) Black iron oxide Ferric oxide, hydrate Ferric oxide Ferrous ferric oxide

Chemical formula (Mol. Wt.) Fe2 O3.H2O (177.70 gm) Fe2 O3 (159.70 gm) FeO.Fe2O3

 Structure: Ferric oxide

Physical Properties:
 Appearance: Iron oxides occur as yellow, red, black, or brown powder. The color












 Melting Point: 1565 C for iron oxide red (Fe2O3 )  Solubility:   Soluble in mineral acids; insoluble in water Soluble In Warm Hydrochloric Acid, Slightly Soluble in Sulfuric Acid.

Iron oxides should be stored in well-closed containers in a cool, dry Place.[3]


Iron oxides have been reported to make hard gelatin capsules brittle at higher temperatures when the residual moisture is 11–12%. This factor affects the use of iron oxides for coloring hard gelatin capsules, and will limit the amount that can be incorporated into the gelatin material. [3]

Specific Purpose:
 Iron oxides are widely used in cosmetics, foods, and pharmaceutical  Its principal application is as colorants and UV absorbers.  As inorganic colorants they are becoming of increasing importance as a result of the limitations affecting some synthetic organic dyestuffs.  However, iron oxides also have restrictions in some countries on the quantities that may be consumed, and technically their use is restricted because of their limited color range and their abrasiveness.  Some iron oxides are widely used in ceramic applications, particularly in glazing. Many metal oxides provide the colors in glazes after being fired at high temperatures.  Black oxide converts ferrous materials into magnetite for corrosion resistance purposes. A grade of hematite called MIO (micaceous iron oxide) is used as anti-corrosion paint (many bridges, Eiffel tower).  Iron oxide is used in magnetic recording, recording sound, pictures, video and computer data on plastic tape or floppy disks.  They may also be used in electro chromic paints.  Combined with aluminum powder, iron oxide forms thermite, which is used in demolition and bomb building.[3][4][1]

Uses of Iron Oxide:
Pigments: Paint, concrete, leather, Shoe Polish, Rubber, Tiles For food and cosmetics: nutritional foods, medicines, lipstick, talcum powder, body and face cream .[2]

Titanium dioxide:

Anatase titanium dioxide; brookite titanium dioxide; color index number 77891; E171; Hombitan FF-Pharma; Kemira AFDC; Kronos 1171; pigment white 6; Pretiox AV-01-FG; rutile titanium dioxide; Tioxide; TiPure; titanic anhydride; titanii dioxidum; Tronox.[3]

Chemistry of Titanium Oxide:
Empirical formula: TiO2 Molecular Weight: 79.88 Structure:

Physical Properties
Appearance: White, amorphous, odorless, and tasteless nonhygroscopic powder. Titanium dioxide may occur in several different crystalline forms: rutile; anatase; and brookite. Of these, rutile and anatase are the only forms of commercial importance. Rutile is the more thermodynamically stable crystalline form, but anatase is the form most commonly used in pharmaceutical applications.[3][1]

Anatase Titanium[1]
(most commonly used in pharmaceutical applications.)

Rutile titanium[1]

Melting point: 1855 °C Boiling point: 2972 °C

 Solubility practically insoluble in dilute sulfuric acid, hydrochloric acid, nitric acid, organic solvents, and water soluble in hydrofluoric acid and hot concentrated sulfuric acid  Solubility depends on previous heat treatment; prolonged heating produces a less-soluble material.

 Titanium dioxide is extremely stable at high temperatures. This is due to the strong bond between the tetravalent titanium ion and the bivalent oxygen ions.  However, titanium dioxide can lose small, unweighable amounts of oxygen by interaction with radiant energy. This oxygen can easily recombine again as a part of a reversible photochemical reaction, particularly if there is no oxidizable material available. These small oxygen losses are important because they can cause significant changes in the optical and electrical. properties of the pigment.

 Titanium dioxide should be stored in a well-closed container, protected from light, in a cool, dry place.[3]

Titanium oxides may interact with certain active substances, e.g. famotidine. Studies have ophthalmic preparations; oral capsules, suspensions, tablets; topical and transdermal preparations). Included in nonparenteral medicines

Specific Purpose:

 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 lightscattering properties that may be exploited in its use as a white pigment and opacifier in powder form, where it is employed as a pigment to provide whiteness and opacity to products such as paints, coatings, plastics, papers, inks, foods, medicines (i.e. pills and tablets) as well as most toothpastes.

 The range of light that is scattered can be altered by varying the particle size of the titanium dioxide powder. For example, titanium dioxide with an average particle size of 230nm scatters visible light, while titanium dioxide with an average particle size of 60nm scatters ultraviolet light and reflects visible light.  In pharmaceutical formulations, titanium dioxide is used as a white pigment in filmcoating suspensions, sugar-coated tablets, and gelatin capsules.  Titanium dioxide may also be admixed with other pigments.  Titanium dioxide is also used in dermatological preparations and cosmetics, such as sunscreens.[1][3]


2. 3. Handbook of Pharmaceutical excipients 6th Ed.(2009) 4. 5. 6. 7. 8.

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