Chemical incompatibility

Definition
 ChemicalIncompatibility is the reaction between
two or more substances which lead to change in
chemical properties of pharmaceutical dosage
form.

 Incompatible chemicals give an
undesired chemical reaction when mixed. This
usually refers to substances that will react to cause
an imminent threat to health and safety through an
explosion, fire, and/or formation of toxic materials.
 We can detect these by our naked eyes.

 Turbidity
 Precipitation
 Crystallization/crystal growth
 Aggregation
 Solidification
 Discoloration
 Thickening
 Change in color, odor and tastes, etc. 
 Types Of Chemical Changes
Oxidation
Hydrolysis
Polymerization
Isomerization
Decarboxylation
Combination
Oxidation
 Addition of oxygen, removal of hydrogen or loss of
electron from atom.
 Factors Leading To Oxidation

 Oxygen
 Light
 Temperature
 pH
 Presence of pre oxidants
 Type of solvent
 Presence of unsaturated bonds
Oxidation
 Measures to prevent oxidation
 Addition of Antioxidants • Addition of chemicals
which form complexes with metals • Protection
from light • Maintenance of pH • choice of suitable
solvent • Storage in low temperature • protection
from air.

 Chemical groups which undergo oxidation:

 Phenolic compounds, Catechol derivatives, Some

antibiotics, Oils and Vitamins
HYDROLYSIS
A chemical reaction in which water is used to break
down a compound; this is achieved by breaking a
covalent bond in the compound by inserting a water
molecule across the bond.

 Ionic hydrolysis: In which the compound is broken into

ions by water. This type take place spontaneously and
is reversible
 Codeine phosphate = Codeine + Phosphate

 Molecular Hydrolysis: In which the molecule it self is

broken down by a minute quantity of water. It is slow
process and irreversible.
 Acetylsalicylic acid = Salicylic acid + Acetic acid
PROTECTION FROM HYDROLYSIS
 Protection from moisture by:
 Packaging with substances impermeable for
moisture
 Addition of substances that absorb water (CaCO3)
 Using of solvent rather than water
 Maintenance of pH by using buffer system
 Formation of absorbable complexes which protect
the drug from the effect of water
 Using of surfactants (micelle formation)
 Reducing of solubility of substance (i.e.
Suspension instead of solution)
POLYMERIZATION
 In polymerization, small repeating units called
monomers are bonded to form a long chain
polymer.
 Formaldehyde to Paraformaldehyde (Polymer:
white precipitate) in heat

 Ampicillinin high temperature forms polymers

which cause allergy

 To avoid this formaldehyde and ampicillin must be

stored in suitable temperature and addition of
methanol 15%.
ISOMERIZATION
It means conversion of drug to its isomer.
Isomers have: identical molecular
formulas yet a different arrangement of
atoms.

Optical
isomerization
Geometric isomerization
ISOMERIZATION
 Optical isomerization: Conversion of optical
active drug into less active
 l-adrenaline is converted to d-adrenaline by
change of ph or temperature. L-adrenaline is
more therapeutically active than d- adrenaline,
although they have the same physical
properties but different arrangement of atoms.

 Geometric Isomerization: Expressed by cis or

trans where Cis is more therapeutically active
than trans (ex.: Vitamin A)
Decarboxylation
 Decarboxylation isa chemical reaction that
removes a carboxyl group and releases carbon
dioxide (CO2). 

 All drugs contain bicarbonate are not sterilized in

high temperature.
 The factors that cause decarboxylation are oxygen,
light, temperature, pH