Pharmaceutical Excipients

Pharmaceutical ingredients
Pharmaceutical ingredients…
• Pharmaceutical ingredients (excipients) are required to
produce a drug substance in a final DF.
• Almost all DFs include excipients.
• The total amount of excipients frequently used is greater

than the amount of the API in a DF.
2
• Excipients have substantial impact on the manufacture and
quality, safety, and efficacy of the drug in a DF.
• Variability in the performance of an excipient came to be

understood as a key determinant of DF performance.
• Excipients are expected to have some defined functional

roles in pharmaceutical DFs.
3
• Some of the functional roles of excipients include:
1) Modulating solubility and F of the API;
2) Enhancing stability of the API in finished DFs;
3) Helping API maintain a preferred polymorphic form or

conformation;
4
4) Maintaining pH and osmolarity of liquid formulations;
5) Acting as antioxidants, emulsifying agents, tablet binders, and

tablet disintegrants;
6) Preventing aggregation or dissociation; and
7) Modulating the immunogenic response of API (e.g., adjuvants)

and many others.
5
• There is some psychologic basis to drug therapy.
• The odor, taste, and color of a pharmaceutical
preparation can play a part.
• Most drug substances are unpalatable and unattractive in

their natural state.
• However, excipients present them to the Pt as

colorful, flavorful formulations attractive to the sight,
smell, and taste.
6
• An appropriate drug has its most beneficial effect when it is
accepted and taken properly by the Pt.
• The proper combination of flavor, fragrance, and color in a
pharmaceutical product contributes to its acceptance.
• Selection of appropriate excipients helps to formulate appropriate
drug
7
Flavoring agents
• Primarily intended to liquids intended for oral

administration.
• Medication in liquid form comes into immediate and direct

contact with these taste buds.
• The taste receptor cells interact with molecules dissolved

in the saliva and produce a taste sensation.
8
• There are four general distinctions of flavor: sweet,
acid/sour, salty, and bitter.
• The selection of an appropriate flavoring agent depends

on several factors, including:
• The taste of the drug substance itself,

• Individuals’ tastes and flavor preferences,
• The age of the intended Pt.
9
• Certain flavoring materials are more effective than
others in masking or disguising the particular taste of a
drug:
• Cocoa-flavored vehicles – for masking the taste of

bitter drugs
• Fruit or citrus flavors – for sour or acid-tasting drugs

• Cinnamon, orange, raspberry – for salty drugs more
palatable.
10
… Pharmaceutical ingredients…
• Geriatric and pediatric Pts are often very different in
their preferences for taste.
• Children prefer sweet candy-like preparations with

fruity flavors
• Adults seem to prefer less sweet preparations with a

tart/sour rather than a fruit flavor.
11
• Flavors must be carefully selected and checked for

stability.
• They can degrade as a result of exposure to light,

temperature, oxygen, water, enzymes,
contaminants, and other product components.
12
• Classification of flavoring agents:

• Natural flavoring agents
Example: Ginger oil, Aloe vera, cinnamon, ……

• Natural identical flavoring agents
Example: Methylaldehyde, Glycerin, alcohol, ……..

• Artificial flavoring agents
Example: Cinnamaldehyde, Benz aldehyde, ……….

Sweetening agents
• A sweetening agent can play a number of important

roles in an oral liquid formulation such as enhancing
flavor, masking bitter taste, and increasing viscosity.
• Two classes of sweeteners:
• Natural Sweeteners (e.g. Sucrose)
• Artificial Sweeteners (aspartame, saccharin)

14
• Typically, the concentration of sweeteners in oral liquids
averages between 30% and 50% of the formulation.
• In some cough or cold syrups, the sweetener content is as high as

80%.
• Concerns – When using higher concentrations of

sweeteners
• Diabetic Pts,
• Risk of microbial contamination and growth,
• Risk of crystallization
15
• Artificial sweeteners are generally very sweet as compare to
sucrose.
• Also called sugar substitutes, low-calorie sweeteners or

non-nutritive sweeteners.
• They offer the sweetness of sugar without the calories.
• This results in a much lower concentration needed in the

formulation.
• Also help to formulate a ‘‘sugar-free’’ formulation for DM

Pts.
16
Coloring agents
• These are used for esthetic purposes.
• Most pharmaceutical colorants in use today are synthetic.
• Generally, colors are used to match the flavor or color

changes of an oral liquid formulation.
17
• Pharmaceutical coloring agents are divided into

two groups:
• Coloring agents that are soluble in water (dyes)
• Coloring agents that are insoluble in water

(pigments)
18
• The amount of colorant generally added to liquid preparations
ranges from 0.0005% to 0.001% depending upon the
colorant and the depth of color desired.
• Because of their color potency, dyes generally are added in

the form of diluted solutions rather than as concentrated dry
powders.
19
• Many coloring agents are poorly compatible or incompatible

with citric acid, ascorbic acid, gelatin, glucose, lactose, sodium
bicarbonate, and saccharose solutions.
• Additionally, several groups of dyes have been associated with

serious adverse effects.
20
• In addition to esthetics and the certification status of a dye, its physical and
chemical properties has also to be considered.
• A prime importance is the solubility of a dye in the

vehicle to be used for a formulation.
• pH and pH stability of the preparation to be colored.
• Dyes can change color with a change in pH.
• Photostability
21
Preservatives
• Pharmaceutical preparations needs preservation against:
• Chemical and physical degradation due to changed environmental

conditions.
• Microbial contamination.
22
• Preparations that provide excellent growth media for microbes
are most aqueous preparations.
• Some desirable features of anti-microbial preservatives:
• A wide spectrum of activity against all bacteria, yeasts and moulds;
• Bactericidal rather than bacteristatic activity;
• Free from toxic, irritant or sensitizing activity;
• High water solubility.

23
• Compatibility with the other ingredients and with the

container;
• Stability and effectiveness over a wide range of pH and

temperatures;
• Free from colour and odour;
• Retention of activity in the presence of large numbers of

microorganisms.
24
25
Buffers and pH Adjusting Agents……acetate, phosphate,
citrate, and glutamate
• Without the ability to control the formulation pH,

• There may be large changes during storage, based on water loss, or
carbon dioxide and oxygen access.
• Most formulations utilize a buffer to control potential

changes in pH.
26
• The selection of a suitable buffer should be based on:
• Whether the acid–base forms are listed for use in liquids

formulations,
• The stability of the drug and excipients in the buffer, and
• The compatibility between the buffer and container.
27
• The stabilizing effect of buffers should also be investigated to

determine the potential reaction between excipients and API.
• There are a number of factors that may also affect the solution
pH such as temperature, ionic strength, dilution, and the
amount and type of cosolvents present.
28
Antioxidants…….Glutathione, butylated hydroxyanisole (BHA)
and butylated hydroxytoluene (BHT)
• The oxidation of an API can be difficult to control due to:
• The presence of trace amounts of impurities, which may be
present from the API or excipient, and
• Oxidation have relatively low activation energies.

29
Antioxidants can be:
• Compounds that can reduce a drug that has been oxidized, or
• Compounds that are more readily oxidized than the agents they are to
protect (oxygen scavengers).
• Antioxidants can also react with free radicals in solution to

stop the free-radical propagation cycle.
30
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Pharmaceutical Excipients

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Pharmaceutical ingredients

• Almost all DFs include excipients.

• The total amount of excipients frequently used is greater

• Variability in the performance of an excipient came to be

• Excipients are expected to have some defined functional

1) Modulating solubility and F of the API;

2) Enhancing stability of the API in finished DFs;

3) Helping API maintain a preferred polymorphic form or

5) Acting as antioxidants, emulsifying agents, tablet binders, and

6) Preventing aggregation or dissociation; and

7) Modulating the immunogenic response of API (e.g., adjuvants)

• Most drug substances are unpalatable and unattractive in

• However, excipients present them to the Pt as

• An appropriate drug has its most beneficial effect when it is

accepted and taken properly by the Pt.

• The proper combination of flavor, fragrance, and color in a

pharmaceutical product contributes to its acceptance.

• Selection of appropriate excipients helps to formulate appropriate

• Primarily intended to liquids intended for oral

• Medication in liquid form comes into immediate and direct

• The taste receptor cells interact with molecules dissolved

• The selection of an appropriate flavoring agent depends

• The taste of the drug substance itself,

• Cocoa-flavored vehicles – for masking the taste of

• Fruit or citrus flavors – for sour or acid-tasting drugs

• Children prefer sweet candy-like preparations with

• Adults seem to prefer less sweet preparations with a

• Flavors must be carefully selected and checked for

• They can degrade as a result of exposure to light,

contaminants, and other product components.

• Classification of flavoring agents:

Example: Ginger oil, Aloe vera, cinnamon, ……

Example: Methylaldehyde, Glycerin, alcohol, ……..

Example: Cinnamaldehyde, Benz aldehyde, ……….

• A sweetening agent can play a number of important

• Two classes of sweeteners:

• Natural Sweeteners (e.g. Sucrose)

• Artificial Sweeteners (aspartame, saccharin)

• In some cough or cold syrups, the sweetener content is as high as

• Concerns – When using higher concentrations of

• Also called sugar substitutes, low-calorie sweeteners or

• They offer the sweetness of sugar without the calories.

• This results in a much lower concentration needed in the

• Also help to formulate a ‘‘sugar-free’’ formulation for DM

• These are used for esthetic purposes.

• Most pharmaceutical colorants in use today are synthetic.

• Generally, colors are used to match the flavor or color

• Pharmaceutical coloring agents are divided into

• Coloring agents that are soluble in water (dyes)

• Coloring agents that are insoluble in water

• Because of their color potency, dyes generally are added in

• Many coloring agents are poorly compatible or incompatible

• Additionally, several groups of dyes have been associated with

• A prime importance is the solubility of a dye in the

• pH and pH stability of the preparation to be colored.

• Dyes can change color with a change in pH.

• Pharmaceutical preparations needs preservation against:

• Chemical and physical degradation due to changed environmental

• Some desirable features of anti-microbial preservatives: