Pharmaceutical Aids

• Pharmaceutical aids can be defined as the inert substances which have no or little
pharmacological effect but are essential to be used in the preparation of pharmaceutical
dosage forms.
• These substances may be required to perform certain functions during successful
manufacturing, storage and transportation, and use of pharmaceutical products.
• These aids may remain in the final product, do not exert any specific action on the body
upon administration of the product or are removed during processing.
Different Pharmaceutical aids
Absorbents Flavouring Agents
Adsorbents Humectants
Acidifiers & Alkalisers Lubricants
Antioxidants Ointment Bases
Binders Preservatives
Buffers Sweetening Agents
Buffering Agent Texturing Agents
Colouring Agents Thickening Agents
Disintegrating Agents Solvents
Diluents Suspending Agents
Desiccants Tonicity Modifiers
Emulsifying Agents Vehicles

Ideal characteristics of pharmaceutical aids

• It should be cheap.
• It should be easily available.
• It should not react with the drug.
• It should be non-toxic.
• It should produce the desired effect.
• It should not change the chemical nature of the drug.
• It should not change the solubility of the drug.

Importance/Application of pharmaceutical aids

• It helps in masking the unpleasant odor, taste, and color etc.
• It insures safe, efficiency, reproducible, and convenient manner of drug delivery.
• Pharmaceutical aids increase the shelf life of the drugs.
• It protects the chemical changes and microbial action of main API; they include
antibacterial agents and antioxidants.
• Due to involvement of the pharmaceutical aids, we design the different form of shape, size
of the dosages form.
• It is overcoming the patients inconvenience and helps in manufacturing, to design attractive
dosages form.

Organoleptic agents
Organoleptic pharmaceutical aids are the components which have no therapeutic value, but
these are essential to formulate any drugs into attractive and acceptable pharmaceutical
product.
Organoleptic substances promote appearance and palatability of pharmaceutical dosage
form and contribute to the acceptance of the pharmaceutical products for easy acceptability by
the patients.
The flavoring agent, sweetening agent and colouring agent are together called as organoleptic
pharmaceutical aids.
Bitter and arid taste drugs are avoided by patients through oral route because of unpleasant
taste and odour as well as colour.
Thus, organoleptic aids are incorporated to improve their colour, flavour and taste,
especially for products prescribed for pediatric and geriatric patients.

Colouring agent
Colourants or colouring agents are mainly used to improve the distinctive appearance of
pharmaceutical dosages form or or elegance to the dosage form., which are helps in the
identification during manufacturing and increase the patient acceptance towards the
pharmaceutical dosages form.
In pediatric and geriatrics coloring agents play a major role and attract the consumer by
providing the aesthetic appearance to dosages form.
Colouring agents may be soluble in the solvent system or suspended as insoluble powders.
All colouring agents used in pharmaceutical formulations must be approved and certified by
FDA as per Drug & Cosmetic Act 1940. Synthetic colourants are classified into three categories
as per FDA (US)
i) Color permitted for Food, Drugs & Cosmetics (FD&C)
ii) Color permitted for Drugs & Cosmetics (D&C)
iii) Color permitted for externally applied Drugs & Cosmetics (external D&C)
 Classification of colouring agents
1) Natural colours: - Natural colors are obtained from plant animal and minerals sources.
a) Minerals: - The colors which are obtained from minerals are frequently termed as pigments
used to color lotion, cosmetics and other pharmaceutical products which are used internally as
well as externally.

• Titanium dioxide: - Naturally occurring titanium dioxide (white) is used in cosmetics

and skin care products such as sunscreen product, titanium dioxide resist
discoloration of the product from UV lights.
• Ferric oxide: - Ferric oxide is chemically stable and color produced by fine grinding
of ores. Red and yellow iron oxide is used in manufacturing of coloured cosmetics.
• Other colouring agents from minerals sources includes Prussian Blue, Lead
Chromates (vivid yellow), Carbon Black, Malachite (copper carbonate hydroxide-
Green), Cinnabar/ vermilion (spicy red orange), Aragonite (basically colourless to
white but present in various colours), Copper Sulphate (Blue).
b) Plants: - The colors which are derived from plants are obtained through the extraction
process.

• Indigo: - Indigo is obtained from the plant Indigofera tinctoria. It is used in

pharmaceutical products. The colour spectrum is 420-450 nm. The colour wavelength
is in between blue and violet.
• Beta carotene: - It is mainly used to colour drugs and cosmetics. It is a carotenoid
comes under natural pigments found in carrots, spinach and broccoli, The orange
colour is masked by green colour of chlorophyll. Carotenoid, a source of vitamin A,
can protect body against oxidative damage and can protect the product from UV light.
Colour source from plants includes

• Flavones: Rutin, Riboflavin’s, Hesperidine, Quercetin - Yellow color

• Saffron, Paprika, & Alizarin-Redish yellow
• Others-Anthocynin (Blue, Red, Purple), chlorophyll (Green), Turmeric (Yellow)
c) Animal colours: -

• Tyrian Purple/ Royal Purple: - It is obtained by oxidation of the secretion of glands of

snails.
• Cochineal: This is obtained from an insect Coccus Cacti and has a brilliant red colour
(carminic acid).
2) Synthetic Colours:
Synthetic colouring agents are used in pharmaceutical and cosmetic products to enhance their
appearance without any toxicity.
(1) Caramel: It is commonly known as burnt sugar. The process of caramelization consists
of heating sugar slowly to around 170 °C (340 °F). As the sugar heats, the molecules break
down and re-form into compounds with a characteristic colour (pale yellow to amber to dark
brown and blackish) and flavour.
(2) Lake dyes: These are aluminum or calcium salts of any water soluble colour. A lake
pigment is manufactured by precipitating a dye with metallic salt.
(3) Coal tar dyes: These are obtained from petrochemicals and coal. These are mostly
aromatic azo dyes. Coal tar dyes are used in medicated shampoo, soap and ointment, etc.
Many coal-tar colors have been found e.g., Naphthol blue black 20470 (BLACK), Brilliant
blue FCS 42090, Indigo Carmine (BLUE), Fast green FCS 42053, Quinazarine Green SS,
Green S (GREEN), Orange G 16230 (ORANGE), Amaranth I.N. 16185, Fast Red E16045,
Erythrosine, Eosin YS, Eosin G, Sudan (I, II, III, IV) (RED), Tartrazine 19140, Sunset
Yellow FCF 15185, Qinoline SS(YELLOW), Resorcin Brown (BROWN).

Flavouring agent: -
The term flavour refers to a mixed sensations of taste, touch, smell, sight and sound of all which
produce a perception of a substance.
flavouring agents are usually used to mask the saline, bitter, sour taste sensations. Flavoring
agent is required to increase patient acceptance. They are generally used in oral dosage form
such as tablets, chewable tablets, syrups, antacids, vitamins, and antibiotics. Flavoring agents
are used in the concentration of 0.5- 0.75%. They are usually stored at 15 to 30 ℃. In pediatric
drugs flavouring agents play a very important role.
Flavouring agents are Thermolabile in nature, so they are added very carefully during
formulation of drugs. They cannot be added to formulation when hot.
Classification of Flavouring agents: - It is classified into two categories
1. Natural Flavouring Agent: - citrus fruits (lemon, orange), spice (cinnamon,
peppermint, ginger), fruits (apple, banana)
2. synthetic flavoring agents: - Benzaldehyde, Cinnamic aldehyde, Coumarin, Ethyl
methyl ketone.
Initially, some natural flavours such as clove, eucalyptus, lemon, mint, orange, wintergreen
etc., were very common for preparation’s meant to oral use & flavours such as jasmine,
lavender, rose etc., for preparation meant for external use.
But now-a-days complete approach is changed to select a flavour. It is evaluated with reference
to drug or vice-versa, for its taste, mouth feel effects & overall impression on the formulations.
 Choice of flavours according to the taste

Taste Flavours
Alkaline Mint, chocolate, vanilla
Sour (Acid) Lemon, orange, anise, raspberry, strawberry
Bitter Mint, chocolate, anise, fennel, cherry
Metallic Grape, lemon, burgundy
Salty Citrus, maple, raspberry, fruity
Sweet Maple, fruity, vanilla, honey

Choice of flavours according to the colour

Colour Flavours
Pink to red Strawberry, cherry, raspberry, apple, rose
Brown Chocolate, honey, caramel, walnut
Yellow to orange Lemon, orange, lime, cherry
Green Mint, banana, Pistachio
White to off white Vanilla, mint, banana, jasmine, spearmint
Violete to purple Grape, liquorice
Blue Mixed fruit, plum, liquorice, blueberry

Sweetening agent: -
Taste is again a chemical sense and its appreciation results from the contact between the taste
possessing materials and the taste buds in the oral cavity.
Four primary tastes sweet, bitter, sour, saline is recognized and all the other tastes are
considered to be admixtures of one or more fundamental tastes in varying degrees.
Sweetening agents are used to impart sweet taste to the bitter pharmaceutical formulations.
They are mainly used for the drugs which are taken via oral route such as tablets, chewable
tablets, and antacids.
Sweeteners are often classified as either caloric or noncaloric. Non-caloric sweetening agents
are preferred for diabetic patients.
Sweetening agents are widely used in Pediatric drugs because children prefer more sweet
drugs.
 Classification of sweetening agents according to calorie
Caloric (contraindicated in Sucrose/table sugar
Diabetic patients) Fructose
D-Glucose
Non-caloric (Sugar free Saccharine (500 times sweeter than sucrose; unpleasant after
sweeteners) taste).
Aspartame (200 times sweeter than sucrose; unstable in
solution).
Acesulfame-K (200 times sweeter than sucrose; Heat stable).
Cyclamate/Na. cyclamate (30 times sweeter than sucrose).
Sorbitol (polyols)
Sucralose (600 times sweeter than sucrose)

Classification of sweetening agents: - It is classified into two categories

1. Natural sweetening agents
2. Artificial sweetening agents
Natural Sweeteners:
Sugars
Sugars such as cane sugar (sucrose), glucose with or without complimentary compounds like
sorbitol, glycerin etc. have been used as sweetening agents from the very beginning.
Sugar coating was an ancient technique and simple syrup has been used as vehicle for many
oral preparations. Sugar often comprises of appreciable portions of solid dosage forms such as
tablets.
Cane sugar (sucrose) is stable between pH 4-8 and is generally used along with glycerin or
sorbitol which reduces its tendency to get crystallized. Sucrose, a low molecular weight
carbohydrate, has been traditionally used as sweetening agent because of several advantages
associated with it: very soluble in water, increases viscosity which impart a product a pleasant
texture in the mouth.
Sucrose {Glucose (1): Fructose (1)}: Can not use in diabetic patients.
Liquid glucose, also known as glucose syrup or confectioner's glucose, is syrup made from
the partial hydrolysis of starch. Glucose syrup is used to sweeten, soften texture and add
volume. Chief drawback with all sugars is their liability to microbial growths.
Sugars such as lactose and maltose, have very limited sweetening power and as such the same
are required to be used in large amounts.
Polyhydric alcohols: sorbitol, mannitol, and to some extent glycerin have sweetening
properties and can be used in preparations for diabetic patients.
Artificial sweeteners
Artificial sweeteners are used in very small amounts of these substances can make formulations
appreciably sweet. Artificial sweeteners include
Saccharin
• Saccharin is marketed as saccharin sodium in which the hydrogen in –NH group is
replaced by Na and which in the crystalline form also has two molecules of water of
crystallization. Sodium saccharine can be easily prepared by dissolving saccharin in
equimolecular quantities of aqueous sodium hydroxide solution followed by crystallization.
Sodium saccharin is nearly 200 times more soluble in water in comparison to saccharin.
• Saccharin is nearly 450-500 times sweeter than normal sugar, bitter aftertaste.
• Saccharin does not undergo metabolism and its potential for causing cancer is determining
factor for its use (carcinogen due to cyclohexylamine formation, possibly by gut).
Aspartame
• 200 times sweeter than sucrose.
• It is the methyl ester of aspartic acid and phenyl alanine. It is hygroscopic in nature and
thus has less stability in presence of moisture.
• Aspartame undergoes metabolism producing phenylalanine and the phenylalanine
metabolism is a problem in persons with phenylketonuria
Sodium cyclamate
• Sodium cyclamate is an artificial sweetener, 30-50 times sweeter than sucrose.
• It is often used with saccharin in a ratio of 10: I to mask the off-tastes of both sweeteners.
• Now, being a carcinogenic, it has been banned.
Sucralose
• It is a non-nutritive non-caloric sweetener.
• It is about 320 - 1,000 times sweeter than sucrose, twice sweeter than saccharin, and
three times sweeter than aspartame.
• It is a sweetener of choice due to its favorable low-calorie,
higher degree of sweetness, stability and safety properties.
Acesulphame
• Approximately 200 times sweeter than sucrose.
 Preservatives
• A preservative is a natural or synthetic chemical that is added to pharmaceutical products
to prevent decomposition by microbial growth or by undesirable chemical changes.
• Preservative is a substance commonly added to pharmaceutical product in order to prolong
its shelf life.
• The addition of preservative to products that have higher water content is essential for
avoiding alteration and degradation by microorganisms during storage.
• Preservatives are added in pharmaceutical preparation to inhibit growth of bacteria, yeasts,
or molds that can cause disease.
• Chemical preservation cannot totally keep products away from spoiling, but they slow
down the spoiling process caused by microorganisms.
• Frozen and canned products often do not contain any preservatives.
Ideal Properties of Preservatives

• It should be non-irritant, non-toxic and physico-chemically stable.

• It should be compatible with other ingredients used in formulation.
• It should act as antimicrobial agent and exert wide spectrum of activity.
• It should be potent and act effectively in small concentrations.
• It should maintain activity throughout product manufacturing, shelf life and usage.
Types of preservatives with Examples and Uses
(I) Based on mechanism of action:
A. Antioxidants:
They are self-reducing agents that oxidize themselves and prevent oxidation of the
components that are sensitive to oxygen.
There are three main types of antioxidants:
1. True Antioxidants (water insoluble)
They act by a chain-termination mechanism by reacting with free radicals, e.g., Butylated
hydroxy anisole (BHA), Butylated hydroxy toluene (BHT)
2. Reducing Agents (water soluble)
They have a lower redox potential than the drug and get preferentially oxidized, e.g., ascorbic
acid. Thus, they can be consumed during the shelf-life of the product.
3. Antioxidant Synergists (chelating agents)
These enhance the effect of antioxidants, e.g., EDTA (ethylenediamine tetra acetic acid),
tetra acetic acid derivatives and salts, di hydroxy ethyl glycine, citric acid, and tartaric
acid.
B. Antimicrobial agents:
• These are agent that acts against gram positive and gram-negative microorganism
responsible for causing degradation of pharmaceutical preparation.
• These agents act against microorganisms by affecting the various cellular portions of
microbial cell and thereby inhibiting their growth.
• Cell wall, cytoplasmic membrane and cytoplasm are such portions of microbial cell
wall that are mostly targeted by the preservatives.
• The antimicrobial agents that have been used as preservatives can be classified into four
major groups: acidic, neutral, mercurial, and quaternary ammonium compounds.

Type of Antimicrobial agent Example with Concentration

Phenol: 0.2–0.5

Chlorocresol: 0.05–0.1

o-phenyl phenol: 0.005–0.01

Acidic
Alkyl esters of Para hydroxy-benzoic acid: 0.001–0.02
(Mostly used for Oral Preparation)
Benzoic acid and its salts: 0.1–0.3

Boric acid and its salts: 0.5–1.0

Sorbic acid and its salts 0.05-0.2

Chlorbutanol: 0.5

Neutral Benzyl alcohol: 1.0

o-phenylethyl alcohol: 0.2–1.0

Thimerosal 0.001–0.1, Nitromersol: 0.001-0.1

Mercurial
Phenylmercuric acetate and nitrate 0.002–0.005

Benzalkonium chloride 0.004–0.02

Quaternary
ammonium compounds Cetyl pyridinium chloride 0.01–0.02

C. Chelating agents:
These are agents which form the complex with the pharmaceutical ingredient and prevent
degradation of pharmaceutical formulation.
The effectiveness of antioxidants can be enhanced through the use of synergists such as
chelating agents.
Chelating agents tend to form complexes with the trace amounts of heavy metal ions
inactivating their catalytic activity in the oxidation of medicaments.
Examples of some chelating agents are ethylene diamine tetra acetic acid derivatives and
salts, di hydroxy ethyl glycine, citric acid, and tartaric acid.
II. Based on source:
(i) Natural preservatives: These are substances obtained from natural sources such as plant,
mineral sources and animals which act as antimicrobial agents.
Examples: Neem oil, sodium chloride, lemon, honey, etc.
(ii) Artificial preservatives: These are agents prepared by chemical synthesis which acts
against various micro-organisms in small concentrations.
Examples: Benzoates, sodium benzoate, sorbates, propionates, nitrites, etc.
Brief description of common chemicals used as preservative
Ethyl Alcohol:

• Ethanol is bactericidal in aqueous mixtures at optimum concentration 70 % v/v.

• Antimicrobial activity is enhanced in the presence of eidetic acid or edentate salts.
Ethanol is inactivated in the presence of non-ionic surfactants and is ineffective against
bacterial spores.
Tocopherols:

• Alpha tocopherol is a source of vitamin E, and is commercially available preservative.

• Amongst tocopherols the beta, delta, and gamma tocopherols are considered to be more
effective as antioxidants.
• Tocopherols are of value in oil-or fat-based pharmaceutical products and are normally
used in the concentration range 0.001-0.05 % v/v.
Sodium Benzoate:

• Sodium benzoate is used as preservative that becomes effective at concentrations of

0.02-0.5 % in oral medicines, 0.5 % in parenteral products, and 0.1-0.5 % in cosmetics.
• It is effective over a narrow pH range and is used in preference to benzoic acid due to
its greater solubility.
• It may impart an unpleasant flavour to a product.
Potassium Benzoate:

• Potassium benzoate's preservative efficacy increases with decreasing pH and is most

effective below pH 4.5.
• However; at very low pH undissociated benzoic acid may produce a perceptible taste
in products.
• It is used as an alternative to sodium benzoate in applications where low sodium content
is desirable.
Methyl Paraben:

• Methyl paraben is used in almost all types of pharmaceutical formulations. It may be

used either alone or in combination with other parabens or with other antimicrobial
agents.
• Methyl paraben is most effective against yeasts and molds over a wide range of pH and
have a broad spectrum of antimicrobial activity.
Propyl Paraben:

• Propyl paraben is a benzoate ester (propyl ester) of 4- hydroxybenzoic acid.

• It is typically used in many water-based cosmetics, such as creams, lotions, shampoos
and bath products.
• It can also be used as a food additive. It acts as an antifungal agent and an antimicrobial
agent.