DRUG INCOMPATIBILITY

Alyana Marie M. Dacanay, RPh, BSCP

Dispensing II
Department of Pharmacy
Saint Louis University
Overview
• Chemical Incompatibilities
• Manifestations
• Remedy
CHEMICAL INCOMPATIBILITY

Alyana Marie M. Dacanay, RPh, BSCP

Dispensing II
Department of Pharmacy
Saint Louis University
Definition
Reaction between two or more substances
which lead to change in chemical properties of
pharmaceutical dosage form
Definition
• Intermediate Incompatibilities
• Delayed Incompatibilities
Tolerated
The reaction is minimized by applying some
suitable order of mixing or mixing the solution
in dilute form but no alteration is made in the
active ingredients of the preparation.
Adjusted
The reaction is prevented by addition or
substitution of one of the reacting substances
with another of equal therapeutic value but
does not affect the medicinal of the preparation
Manifestations
A. Oxidation
B. Hydrolysis
C. Acid-Base Reaction
D. Isomerization
E. Photochemical Degradation
A. Oxidation
Oxidation is defined as loss of electrons or
gain of oxygen
Auto-Oxidation
It is a reaction with oxygen of air which occur
spontaneously without other factors.
Oxidants
Substance that triggers oxidative stress
by increasing free radicals.
Factors
• Pharmaceutical Dosage form
• Oxidants
• Types of solvent used
• Presence of unsaturated bonds
• Some chemical groups
Remedy
• Use of antioxidants
• Addition of chelating agent
• Dispense separately
B. 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
Types
• Ionic Hydrolysis
• Molecular Hydrolysis
Chemical Groups which
undergo Hydrolysis
• Esters (R-COR)
• Amides (R-C-NH-R)
• Nitrites (NO3, NO2, N2O)
Factors
• Presence of water
• pH
• High temperature
Remedy
• pH control
• Avoid water or moisture formulation
• Using of solvent rather than water
• Formation of complexes
• Using of surfactants
C. Acid-Base Reaction
• Precipitation
• Gas Formation
Precipitation
• Most medicaments in use are often salts of
weak acids or bases.
• If a solution of a salt of a weakly acidic drug is
acidified, the free acid may be precipitated.
Gas Formation
• Gas may be evolved due to chemical reaction
between the ingredients of a formulation.
• Example includes carbonates or bicarbonates
with an acid or acidic drug resulting in the
evolution of carbon dioxide
D. Isomerization
• Isomers have
§ Identical molecular formulas
§ A different arrangement of atoms
Types
• Optical Isomerization
• Geometric Isomerization
Optical Isomerization
• Conversion of optical active drug into less
active.
• Example: L-Adrenaline is converted to d-
adrenaline by change of pH or temperature
Geometric Isomerization
• Cis
§ Means the groups A in the same direction
• Trans:
§ Means the group A in opposite direction
Geometric Isomerization
E. Photochemical
Degradation
Remedy
• Protect from light
• Given at night
END OF PART 2

Alyana Marie M. Dacanay, RPh, BSCP

Dispensing II
Department of Pharmacy
Saint Louis University