MP2 Excipients in SDFs 1 & 2

Ideal excipient attributes

1. Chemically and physically stable

2. Low microbial content

3. Compatible with other drugs and excipients in the formulation

Excipient sources and examples

Natural sources: - Mineral oil and water

Semi-synthetic sources: - Cellulose derivatives

Synthetic sources: - Surfactants (poloxamer)

Solvent

Medium in which the drug is dissolved, easily swallowed and readily moves across biological membranes

Grades of water

1. Purified

2. Highly purified

3. Water for injection

4. Sterilised water for injection

When is purified water used (DI or distilled)?

When there's no requirement for sterility

When is highly purified water used?

When water of a high biological quality is needed (except when water for injection is required)

Where is water for injection used?

Parenterally (must be spore free!)

Where is sterilised water for injection used?

Parenterally (must be formally sterilised in a container to ensure sterilisation)

Cosolvent

Solvent used to increase lipophilicity of a solvent like water so that it can dissolve lipophilic drug

Cosolvent concerns

- Toxicity

- Flammability

- Stability

Alcohol cosolvents include

1. Ethanol

2. Propylene glycol (PG)

3. Glycerol

4. Low Mr polyethoxylates (PEGs)

Ethanol is the most...

...commonly used cosolvent

What is propylene glycol (PG)?

Polyhydric alcohol which is a widely used (co)solvent in SDFs

What is glycerol?

Polyhydric alcohol (3 -OH groups per molecule) used to prevent cap-locking (like sorbitol)

Fixed oil

Non-volatile (doesn't evaporate) oil that's fixed in position of vegetative origin e.g. olive oil

How are esters used as a solvent?

Esters e.g. ethyl oleate decreases viscosity. It's a synthetic oil used in IM injections.

Acidifiers

substance that lower pH by providing H+ ions

Alkalizers

substance that raises pH by providing OH- ions

Solubiliser

substance that increases apparent solubility of a drug in water so the dose is in a manageable size unit and readily moves across membranes e.g. poloxamer, polysorbates

Oxidation is defined as either

Increase in carbon: oxygen ratio OR

Decrease in carbon: hydrogen ratio

True antioxidant

Substance added that rapidly reacts with free radicals, blocking propagation e.g. Cysteine

Reducing antioxidant

Substance added that's more readily oxidised than the drug/excipient that required protection e.g. sodium bisulphite

Synergist

Enhances activity of antioxidants e.g. EDTA

Wetting agent

Substance that permits the spreading of a liquid over a solid and displacement of gas by lowering surface tension e.g. polysorbate

Levigating agent

Substance that facilitates wet grinding to reduce particle size e.g. mineral oil

Humectant

Substance that binds to water to prevent evaporation by lowering VP to prevent drying out. Also a crystallisation inhibitor e.g. glycerol, sorbitol, PG

Clarifier

Substance, typically a polymer added to a solution to bind up all the solid mass to make it easy to remove by filtration e.g. crospovidone

Preservative

Substance added to extend shelf life of a medicine e.g. Benzoic acid and sorbic acid are antimicrobial, antifungal preservatives

2 types of preservatives

1. Antimicrobial preservatives e.g. Benzoic acid and Sorbic acid

2. Chemical preservatives e.g. antioxidants

What conditions do microorganisms favour?

Slightly basic conditions

Where there's no water...

...bacteria won't grow

Preservative requirements

1. Non-toxic

2. Broad spectrum

3. Chemically stable

Benzoic acid water solubility

Sparingly soluble in water as it's only active in it's unionised form

What causes a sour taste?

H+ ions

What causes a salty taste?

Simultaneous cation and anion presence

What causes a bitter taste?

High Mr organic species

What causes a sweet taste?

Polyhydroxy compounds e.g. sugars

Acceptable taste requirements

- Immediate taste identity

- Acceptable mouth feel

How to impart optimal taste

1. Blending

2. Overshadowing

3. Physical methods

4. Chemical methods

5. Physiological methods

Blending

Use of flavour that blends with the drug's taste e.g. orange to mask acid

Overshadowing

Use of a more intense flavour

Physical methods

Formulating suspension, emulsion, viscosifiers

Chemical methods

Adsorption or complexation of drug

Physiological methods

Cooling sensation of mannitol (caused by the desensitisation of taste buds) or the sialagogue action of citric acid

N.B!! Sialagogue

Substance added to stimulate saliva production to minimise the residence time of unfavourable drug/excipient taste e.g. citric acid

Viscosity enhancer

Substances that render preparation more resistant to flow e.g. syrups and polyhydric alcohols

What do viscosity enhancers optimise?

Pourability, mouth feel, and ensure a good dosage amount on the spoon