5. PHARMACEUTICAL AIDS

PHARMACEUTICAL AIDS

The term pharmaceutical aid refers to materials or chemicals without a pharmacological activity of their own but is the most important component of pharmaceutical production. In the formulation of preparation, preservation, and transportation, pharmaceutical aids are essential. It has no specific effect on the human body. It is added to pharmaceutical products to mask their unpleasant taste or smell in order to boost patient adherence towards the medication. Various pharmaceutical aids are employed in the preparation of various dosage forms, such as tablets, capsules, emulsions, suspensions, etc. Agents for coloring, flavoring, sweetening, suspending, emulsifying, and lubricants are some examples of pharmaceutical aids.

FUNCTIONS OF PHARMACEUTICAL AIDS

1. Modify the API’s solubility and bioavailability.
2. Help APIs to maintain their polymorphic forms or conformations.
3. Help liquid dosage forms in maintaining their pH or osmolarity.
4. Act as antioxidants, emulsifying agents, aerosol propellants, tablet binders, and tablet disintegrants.
5. Prevent aggregation or dissociation (e.g., of protein and polysaccharide actives).
6. Modulate the APIs immunogenic responses (e.g., adjuvants).
7. Make up the bulk of a potent drug formulation to obtain an accurate dosage form.
8. Improve patient compliance.
9. Enhance API’s bioavailability.
10. Modify the formulation’s safety and effectiveness during its use and storage period.

CHARACTERISTIC FEATURES OF AN IDEAL PHARMACEUTICAL AID

1. Non-reactive and inert
2. Chemically stable
3. Non-toxic
4. Requires less equipment and process-sensitive
5. Organoleptically acceptable
6. Efficient with respect to its use
7. Economical

CLASSIFICATION OF PHARMACEUTICAL AIDS

Pharmaceutical Aids	Functions	Examples
Acidulants	Gives sour taste, helps in gel formation, preservative	Tamarind, lemon juice, tomatoes
Colouring agents	Provides colour to pharmaceutical preparations	Caramel, turmeric, saffron, Indigo
Disintegrating Agent	Used in tablet manufacturing; breaks tablets into small pieces	Starch, CMC, Microcrystalline cellulose
Diluents	Diluting agent; increases content uniformity	Cinnamon water, peppermint water, corn oil, sesame oil, glucose, lactose
Emulsifying Agent	Allows fat to be evenly distributed in water as emulsion	Acacia, Agar, bentonite, gelatin
Suspending Agent	Used to reduce suspension	Acacia, Agar, bentonite, gelatin
Filter Aids	Used for filtration of colloids, fine particles, gel	Talc, bentonite, diatomite
Flavouring agents	Helps in masking unpleasant tastes	Cardamom, rose, cocoa, lemon, orange
Lubricants	Reduces friction between two surfaces; increases efficiency	Mg stearate, talc, cocoa butter
Sweetening Agent	Gives sweet taste to food	Honey, saccharin, glycyrrhiza
Thickening agent	Improves viscosity and stability	Pectin, tragacanth, methyl cellulose
Adhesives and binders	Imparts cohesive qualities to powdered materials	Acacia, gelatin, dextrose, sorbitol, dibasic calcium phosphate dehydrate
Glidants	Improves flow characteristics of powder mixture	Colloidal silicon dioxide (Carbosil), asbestos free starch, corn starch
Sorbents	Helps in moisture proofing	Silica gel, activated carbon, clay
Coating Materials	Protects tablet ingredients from deterioration; helps swallowing	HPMC, synthetic polymers, shellac, corn protein Zein, gelatin, povidone
Solvents	Helps in dissolving API	Water, alcohol, acetic acid, acetone
Co-Solvents	Increases solubility of solute in solvents	Ethanol, sorbitol, glycerine, propylene glycol
Buffers	Helps to maintain pH of formulation	Phosphate buffers, acetate buffers, citric acid phosphate buffers
Antimicrobial agents	Prevents microbial growth in formulations	Benzyl alcohol, butyl paraben, phenol, thiomersal
Preservatives	Helps in preserving the formulation	Benzyl alcohol, propyl paraben, methyl paraben, sodium benzoate
Antioxidants	Helps to prevent oxidation	Butyl hydroxy toluene, butyl hydroxy anisole, ascorbic acid
Solubilisers	Enhances solubility of API in ointments	Lanolin, cholesterol or cholesterol esters
Gelling Agents	Helps in preparing gels	Carbomer 934, Pemulen, carboxy methyl cellulose, xanthan gum
Emollients	Modifies vehicle/skin characteristics to assist penetration of API	Glycerine, mineral oil, petrolatum, isopropyl palmitate

ORGANOLEPTIC AGENTS

Organoleptic agents are the important agents of pharmaceutical aids. These agents include a wide variety of additives, such as colouring, flavouring and sweetening agents. They are broadly employed in pharmaceutical as well as cosmetic formulations as they serve a major purpose of increasing patient compliance by improving their characteristics and aestheticity.

Colours / Colouring Agents

In pharmacy, colourants or colouring agents obtained from plants, animals and mineral sources are particularly used for providing colour so as to impart pleasing appearance to drugs and cosmetics. The Drugs and Cosmetics Act 1940 and Rules 1945 in India have permitted the use of the following colours in drugs:

• Coal Tar Colours: Amaranth, green S, orange G, patent blue and tartrazine
• Lakes: Aluminium or calcium salts of any water soluble food dye

Classification of Colouring Agents

• Natural Colours: Mineral colours (red/yellow ferric oxide, titanium dioxide, carbon black), Plant colours (chlorophyll, β-carotene, alizarin, indigo, anthocyanin), Animal colours (tyrian purple, carminic acid)
• Synthetic Colours: Perkin’s purple (Mauveine, 1856); permitted colours in India – Annatto, carotene, chlorophyll, cochineal, curcumin, titanium dioxide, turmeric, saffron, paprika; Red 3, Red 40, Yellow 5, Blue 1, Blue 2

Selection Criteria for Colouring Agents

• Certification status and aesthetics of dye
• Physicochemical properties of dye
• pH and pH stability of liquid preparations
• Photo stability of dye
• Personal preference of consumer population

Advantages of Colouring Agents

• Provide grace and better eye-appealing character
• Help in fast recognition of medicine for poisoning treatment
• Help doctor in identifying drugs given during previous treatment
• Help in sale of medicine by familiarisation of colour

Uses of Colouring Agents

• For Identification: Tablets, capsules, medicated surgical dressings, medical gas cylinders (e.g., blue coloured anaesthetic trichloroethylene)
• To Increase Patient Acceptability: Flesh-tinted powders, cherry-red cough mixtures, bright-coloured tonics
• To Produce Standard Preparations: Ferric oxide coloured calamine

Flavours / Flavouring Agents

Flavouring agents play a vital role in masking the disagreeable taste of liquid dosage forms used for oral purposes. In order to increase patient compliance, certain antibiotics masticated in the mouth and chewable tablets of antacids are generally sweetened and added with flavouring agent.

Suitable Masking Flavours for Various Product Tastes

Taste of Product	Suitable Masking Flavour
Salty	Apricot, butterscotch, liquorice, peach, vanilla
Bitter	Anise, chocolate, mint, passion fruit, wild cherry
Sweet	Vanilla, fruits, berries
Sour	Citrus fruits, liquorice, raspberry

Classification of Flavouring Agents

• Sweetening Agents: Sucrose, invert syrup, saccharin sodium, sorbitol, treacle
• Flavoured Syrups: Fruit-flavoured syrup, cocoa syrup
• Aromatic Oils: Anise, caraway, cinnamon, clove, dill, ginger, lemon, orange, peppermint
• Synthetic Flavour: Benzaldehyde, vanillin

Sweeteners / Sweetening Agents

Classification of Sweetening Agents

• Nutritive Sweetener: Fructose (4Kcal/gm), sugar alcohols (sorbitol, mannitol, lactilol)
• Non-Nutritive Sweetener (Artificial): Aspartame, saccharin, cyclamate, alitame

Uses of Sweetening Agents

• Saccharin: Candies, drinks, toothpaste
• Aspartame: Table-top sweetener, variety of foods
• Mannitol: Asthma test, decrease intracranial/intraocular pressure, calculate GFR, monitor pulmonary symptoms in cystic fibrosis
• Lactose: Additive and filler for structure and consistency
• Sorbitol: Laxative to relieve constipation, urologic irrigating fluid, pharmaceutical sweetener

PRESERVATIVES

A preservative is a natural or synthetic substance that is added in the products like foods, pharmaceuticals, paints, biological samples, wood, etc., to avoid decomposition by microbial growth or by unwanted chemical changes. These are chemicals that are commonly added to many foods and pharmaceutical products in order to extend their shelf life.

Ideal Properties of Preservatives

1. Non-irritant
2. Non-toxic
3. Physical and chemical stability
4. Compatible with other ingredients
5. Good antimicrobial agent with wide range of activities
6. Potent – acts in minor concentration
7. Maintains activity during product manufacturing, shelf life and usage

Types of Preservatives

Based on Mechanism of Action

• Antioxidants: Vitamin E, Vitamin C, BHA, BHT
• Antimicrobial Agents: Benzoates, sodium benzoate, sorbates
• Chelating Agents: Disodium EDTA, polyphosphates, citric acid

Based on Source

• Natural Preservatives: Neem oil, salt (sodium chloride), lemon, honey
• Artificial Preservatives: Benzoates, sodium benzoate, sorbates, propionates, nitrites

Mechanism of Action

1. By modifying the permeability of the membrane
2. By denaturing the enzymes and other cellular proteins
3. By carrying out oxidation of cellular constituents
4. By the process of hydrolysis

Selection Criteria for Preservatives

1. Broad spectrum effectiveness against contaminating organisms
2. Stable and highly effective even in small concentrations
3. Should not react with other ingredients to form harmful substances
4. Easily soluble in the desired vehicle
5. Odourless, tasteless, and colourless
6. Physicochemical properties should not get affected by pH
7. Partition coefficient should be towards the aqueous phase in biphasic systems
8. Should not produce toxic, irritant and sensitising effects

Uses of Preservatives

• Ethanol: Disinfectant, antimicrobial preservative in solutions
• Alpha Tocopherol: Preservative of colours and flavours; delays deterioration, rancidity, discolouration
• Benzoic Acid: Preserving foodstuffs, drugs and cosmetics (0.1% w/v)
• Sodium Benzoate: Antimicrobial preservative; oral medicines (0.02-0.5%), parenteral (0.5%), cosmetics (0.1-0.5%); tablet lubricant (2-5% w/w)
• Parahydroxy Benzoate (Parabens): Methyl, ethyl, propyl parabens – widely used in syrups and pharmaceutical preparations
• Ascorbic Acid: Antioxidant (0.01-0.1% w/v); pH adjuster for injections
• Phenol (Carbolic Acid): Bactericide in multi-dose injections, gargles, mouth washes (0.5% w/v); ear drops, oily injections (6.4% w/v)
• Sodium Chloride: Produces isotonic solutions; channelling agent, osmotic agent, porosity modifier in tablet coatings
• Methylparaben: Antimicrobial preservative in cosmetics, food, pharmaceuticals; used alone or with other parabens or propylene glycol (2-5%)