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LECTURE
-8
Incompatibilities
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Objectives
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At the end of this chapter students
will able to:
Define Incompatibilities
Identify types of Incompatibilities
Describe Prevention mechanism of
Incompatibilities
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Introduction
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An incompatibility: undesirable drug
interaction with one or more
components of a formulation, resulting in
changes in:
physical, chemical or therapeutic properties
of the dosage form
pharmaceutical incompatibility : mixing
of two or more antagonistic substances and
an undesirable product is formed which may
affect the
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safety, efficacy and appearance of
Incompatibility
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Excipients and their concentration in a
formulation are
selected based not only on their functionality,
but also
on the compatibility between the drug and other
excipients.
Pharmaceutical incompatibility may occur
during
formulation, manufacturing, packing compounding
and dispensing or administration of drugs.
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Incompatibilities determining
mechanism
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Types Incompatibility
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Drug -excipient interactions can be
classified simply as
physical
chemical, , and
physiological/biopharmaceutical
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A) PHYSICAL INCOMPATIBILITY
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When two or more than two substances are
combined together, physical changes take
place and an unacceptable product is
formed.
These changes which occurs as a result of
physical incompatibility are usually visible
and can be easily corrected by applying the
pharmaceutical skill obtain to a product of
uniform dosage, an attractive apperance &
having satisfactory therapeutic activity.
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A) PHYSICAL INCOMPATIBILITY…
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Examples of physical incompatibilities
Immiscibility
Insolubility
Precipitation
Liquefaction
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A) PHYSICAL INCOMPATIBILITY…
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1. IMMISCIBILITY
Oils and water are immiscible with each
other.
Example:
Castor oil-15ml and Water-60ml Make on
emulsion.
In this prescription castor oil is immiscible
with water.
To overcome this incompatibility an
emulsifying agent is used to make a good
emulsion. 03/06/2025
A) PHYSICAL INCOMPATIBILITY…
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2. INSOLUBILITY
Insolubility means the inability of material to
dissolve in a particular solvent.
Example:
Phenacetin-3g, Orange syrup-12
Caffeine-1g ml
Water up to -
In this prescription Phenacetin is an indiffusible
90ml
substance. Compound powder of tragacanth or
mucilage of tragacanth is used as a
suspending agent to make a suitable
suspension. 03/06/2025
A) PHYSICAL INCOMPATIBILITY…
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3. PRECIPITATION
A drug in solution may be precipitated, if
the solvent in which it is insoluble is added
to the solution.
Example:
The resins are insoluble in water. When the
tincture containing resins is added in water,
resin agglomerates forming indiffusible
precipitates.
This can be prevented by slowly adding the
undiluted tincture with vigorous stirring to the
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diluted suspension Or
A) PHYSICAL INCOMPATIBILITY…
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4. LIQUEFACTION
When certain low melting point solids are mixed together,
a liquid or soft mass known as “eutectic mixture” is
produced.
This occurs due to the lowering of the melting point of mixture
to below room temperature and liberation of water of
hydration.
Many chemicals form hydrates, compounds with water of
crystallisation.
The medicaments showing this type of behavior are
camphor, menthol, thymol, phenol, chloral hydrate and
aspirin
This type of substance create problem when they are
dispensed in powder form.
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A) PHYSICAL INCOMPATIBILITY…
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Example:
Menthol-5g Ammonium chloride-30g
Camphor-5g Light magnesium
carbonate-60g
In this prescription menthol, camphor and
ammonia chloride get liquefied on mixing with
each other.
To dispense this prescription, menthol camphor
and ammonium chloride are triturated together
to form liquid.
o Add light magnesium carbonate and mix it
thoroughly to make free flowing powder.
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Prevention physical
incompatibilities
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An attractive incompatibilities’ may be
corrected by using any one or more of the
following method.
Change the order or mixing of the
prescription
Adding Emulsification
Adding of suspending agent
Change in the form of ingredients, by adding
substitution or omission of therapeutically
inactive substance
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B. CHEMICAL INCOMPATIBILITY
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Chemical incompatibility may be as a
result of chemical interactions between the
ingredients of a prescription and a toxic or
inactive product may be formed.
The most common reactions observed in
pharmaceuticals are:
hydrolysis, oxidation, photo-
degradation, dehydration and
isomerization.
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B. CHEMICAL INCOMPATIBILITY…
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Prevention of Chemical Incompatibility:
1) Tolerated: In tolerated incompatibilities.
The chemical interaction can be minimized by changing
the order of mixing or mixing the solutions in dilute
forms but no alteration is made in the formulation.
2) Adjusted: In adjusted incompatibilities the
chemical interaction can be prevented by
addition or substitution of one of the reacting
ingredients of a prescription with another of equal
therapeutic value.
o Example: Caffeine citrate can be substituted with caffeine in
sodium salicylate and caffeine citrate mixture.
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C. Physiological/
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biopharmaceutical interactions
For examples, the interaction between
tetracycline antibiotics and calcium and
magnesium ions.
Polyols (e.g., sorbitol and xylitol) increase
GIT motility, and as result reduce site
specific absorption of drugs such as
metoprolol
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