IN- VITRO DRUG

INTERACTIONS
THE INCOMPATIBILITIES
 01
Introduction
In vitro drug interactions
may be defined as those
interactions which occur
outside the body.
IN VITRO DRUG INTERACTIONS

• Interactions between drugs in

vitro (eg, precipitation when
mixed in solutions for
intravenous administration) are
usually classified as drug
incompatibilities, not drug
interactions.
 INCOMPATIBILTIES

incompatibility is defined as a change

resulting and an undesirable product is
formed, which may affect the safety,
efficacy appearance and stability of the
pharmaceutical product
INCOMPATIBILITIES OCCUR DURING
 Compounding
The incompatibilities may be  Formulation
detected by changes in the
 Manufacturing
physical, chemical, and
therapeutic qualities of the  Packaging
medicine.  Dispensing
 Storage
 Administration of
drugs(vivo)
 TYPES OF INCOMPATIBILTIES

I. PHYSICAL INCOMPATIBILITIES
II. CHEMICAL INCOMPATIBILITIES
III. THERAPEUTIC INCOMPATIBILITIES
PHYSICAL INCOMPATIBILITIES
When two or more than two substances are combined, a
physical change takes place, and an unacceptable product is
formed. Interaction between two or more substances which
may lead to change in color, odor, taste, viscosity and
morphology. It is also called as pharmaceutical incompatibility
MANIFESTATIONS OF PHYSICAL
INCOMPATIBILITY

A. Insolubility:-insolubility of prescribed agents

in vehicle
B. Immiscibility:-Immiscibility of two or more
liquids
C. Precipitation:-It occurs due to solvent is
insoluble when it is added to solution
D. Liquefaction:-Liquefaction of solids mixed in
a dry state (called eutaxia).
A. Insolubility
It means the inability of material to dissolve in a particular
solvent system. Majority of incompatibilities is due to
insolubility of the inorganic as well as organic compounds
in particular solvents
A.
The following factors affect the solubility of prescribed
agent in vehicle and may render it less soluble

 Change in PH
 Milling
 Surfactant
 Chemical reaction
 Complex formation
 Co-solvent
A.
The following factors affect the solubility of prescribed
agent in vehicle and may render it less soluble
 Any change in previous factors may lead to precipitation of drugs and
change in their properties
 Substances like chalk, acetyl salicylic acid, succinyl sulphathiazole, zinc
oxide, and calamine are the common examples of in diffusible solids.
 Some tinctures containing resins or chlorophyll may provide precipitation
when added to the aqueous system
A. EXAMPLE PRESCRIPTION
MIXTURE OF PREPARED CHALK

Rx Causes: Chalk powder is not soluble in

Chalk powder –2g water. It gets precipitated when added to
Tincture catechu – 2ml aqueous medium. These precipitates are
Cinnamon water – 2ml found in diffusible in nature which results in
physical incompatibility.
A. EXAMPLE PRESCRIPTION

MIXTURE OF PREPARED
CHALK

Rx Remedy: Use of suspending agents is

Chalk powder –2g necessary to suspend the precipitated
Tragacanth – 0.4g chalk particles. Generally, 2% W/V of
Tincture catechu – 2ml
compound tragacanth powder is
Cinnamon water up to 30ml
recommended as suspending agent.
B. Immiscibility
When two such ingredients are combined resulting in a non-
homogenous product, such ingredients are called immiscible to
each other and the phenomenon is called immiscibility. This
manifestation appears clearly in emulsions, creams, lotions, some
types of ointments. Separation in two phases is noticed in this
pharmaceutical dosage form. Storage must be in room
temperature to prevent separation
B. The following factors lead to immiscibility

 Incomplete mixing
 Addition of surfactant with;
-Unsuitable concentration
-False time of addition
-Unsuitable for the type of emulsion
 Presence of micro – organisms
-Some bacteria grow on constituents of mixture
B. EXAMPLE PRESCRIPTION
Castor oil emulsion Causes: In this prescription castor oil is
Rx
immiscible with water due to high interfacial
Castor oil – 15ml tensions, which is a sign of incompatibility.
Water – 60ml

Castor oil emulsion

Rx Remedy: To overcome this type of
Castor oil – 15ml incompatibility emulsification is necessary
Acacia – 2% W/V with the help of an emulsifying agent.
Water– up to 60ml
 C. Precipitation
Solubilized substances may precipitate from it solution if a non-solvent
for the substances is added to the solution.

Example:
• Resins are insoluble in water Alcoholic solution of resins + water
=precipitated resins.
• Aqueous dispersions of hydrophilic colloids (polysaccharide mucilage
+ high concentration of alcohol or salts) =precipitated colloids.
C. EXAMPLE PRESCRIPTION
Lotion of compound tincture of
benzoin
Rx
Tincture benzoin compound – 5g
Glycerin – 10ml
Rose water up to 100ml
Causes: Tincture benzoin compound
contain resins. This change in solvent
system results in an unavoidable
precipitate.
Remedy: Addition of tincture with rapid
stirring yields a fine colloidal
dispersion. So there is no need of any
suspending agents.
 D. Liquefaction
• When certain low melting point solids are mixed together, a liquid or
soft mass know as eutectic mixture is produced. This occurs due to
the lowering of the melting point of the mixture to below room
temperature and liberation of hydrates .
• If such conditions take place, compounding such powders becomes
difficult since the ultimate mixture turns to liquid. The medicaments
showing this type of behavior are camphor, menthol, phenol, thymol,
chloral hydrate, aspirin, sodium salicylates, etc……
D. EXAMPLE PRESCRIPTION

Insufflations Causes: This mixture is a physical incompatibility

Rx because both the ingredients in the prescription are
Menthol – 5g liquefiable of mixed together.
Camphor – 5g
Water – 60ml
Remedy: These substances can be dispensed by any
one of the following method. Triturate together to form
Rx liquid and mixed with an absorbent (light kaolin,
Rx
Menthol magnesium carbonate) to produce the following powder.
Menthol –– 5g
5g
Camphor The individual medicaments is powdered separately and
Camphor –– 5g5g
Light mixed with an adsorbent and then combined together
Light kaolin–
kaolin– 0.2g
0.2g
tightly and filled in a suitable container
 CHEMICAL INCOMPATIBILITIES
Reaction between two or more substances which lead to
change in chemical properties of pharmaceutical dosage
form. As a result of this a toxic or inactive or product may be
formed
Factors to consider

Mercury
Mercury is the closest planet to the Sun and
the smallest one in the Solar System—it’s
only a bit larger than the Moon

Venus
Venus has a beautiful name and is the
second planet from the Sun. It’s hot and has
a poisonous atmosphere
OCCURANCE
Chemical incompatibilities occur, due to the
chemical properties of drugs and additive like;

Double
Double
pH
pH change
change decomposition
decomposition

Oxidation-reduction
Oxidation-reduction Complex
Complex
reactions
reactions formation
formation

Acid-base
Acid-base
hydrolysis
hydrolysis
A picture is worth
a thousand words
Clinical trial

Preclinical Phase 1 Phase 2 Phase 3

● Mercury is the ● Venus has a ● Despite being ● Jupiter is a gas
smallest planet beautiful name, red, Mars is giant and the
but it’s hot actually cold biggest planet in
● Mercury is a the Solar System
rocky planet ● Venus is hotter ● Mars is full of
than Mercury iron oxide dust, ● Jupiter doesn’t
which gives the have a surface
● Venus has a toxic planet its color
atmosphere
Trial timeline
Mercury is the smallest Despite being red, Mars is Neptune is very far from
planet of them all a cold place the Sun

Research Experimentation Conclusions

A
A B
B C
C D
D EE
Preclinical Results
Jupiter is the biggest Saturn is a gas giant with
planet of them all several rings
Phase 1

Young healthy people 80% Success

20-80 participants
Mainly female
Secondary Venus ha extremely
Effects high temperatures

Results Goal 6 months

Venus has a beautiful name and is the Study the safety of Experimentation
second planet from the Sun medication time
Alcoholism treatment tendency
Mercury
60%
60% Mercury is a
small planet

Venus
60%
60% Venus has a
beautiful name

Mars
60%
60% Mars is actually
a cold place

Follow the link in the graph to modify its data and then paste the new one here. For more info, click here
Results

Experiment A Experiment B
Outcome Outcome

Groups Test 1 Test 2 Test 3 Test 1 Test 2 Test 3

Group 1 315 584 328 357 249 365

Group 2 587 459 569 459 957 398

Group 3 124 684 398 589 245 358

Awesome
words
Results analysis
Mars Jupiter Mars
Mars is Jupiter is a 01
01 Mars is
actually cold gas giant actually cold

987,345 Jupiter
Jupiter is a gas giant
02
02 Jupiter is a
gas giant

Mars 60% Mercury

03
03 Mercury is
Jupiter 40% very small
150,000
Big numbers catch your audience’s attention
Conclusions
Venus has a beautiful name and is the second planet
from the Sun. It’s terribly hot—even hotter than Mercury
—and its atmosphere is extremely poisonous
This is a map

Mercury Mars
Mercury is the Despite being
closest planet red, Mars is
to the Sun very cold

Venus Jupiter
Venus is the Jupiter is the
second planet biggest planet
from the Sun of them all
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