CHEMICAL

INCOMPATIBILITIES
CHEMICAL INCOMPATIBILITIES
Occurs as a result of:
◦ Chemical interaction among the ingredients of a prescription.
Incompatible mixtures:
• Should not be dispensed without correction, unless so intended by the
physician
Classification of Chemical Incompatibilities
A. OXIDATION
Problem with:
Stock solutions, inadequate formulated manufactured products, certain Rx mixture may also
oxidize when exposed to:
◦ Air Undergo auto-oxidation (chain reaction type of
oxidation):
◦ Temperature • Oils and fats, phenolic substances, aldehydes &
◦ Over dilution vitamins – used as antioxidants themselves
◦ Presence of catalysts REMEDY:
Controlled by addition of still more reactive inhibitors to:
◦ Excessive storage
• Provide electrons and
◦ Light • Receive the excess energy possessed by the activated
◦ Incorrect pH adjustment molecules
Classification of Chemical Incompatibilities
B. REDUCTION
Less common in Rxs although:
- Silver, mercury and gold salts may be reduced by light to metallic form

C. RACEMIZATION
Conversion of an optically active form to an optically inactive form without
changing chemical constitution produces reduced pharmacological activity.
Classification of Chemical Incompatibilities
D. PRECIPITATION
Two or more pharmaceuticals are combined
- Formation of insoluble substance which precipitates from solution
Flocculent Precipitates
- Develop several days after a stock solution is prepared
- Evidence of the growth of yeast, molds or bacteria
- Growth due indirectly to a chemical incompatibility if the
preservative system is inactivated by a chemical reaction.
Classification of Chemical Incompatibilities
E. EVOLUTION OF GAS
Formed by chemical reaction between ingredients.
Example: effervescence caused by the liberation of carbon dioxide from the reaction of
carbonates and acids in aqueous media

F. COLOR CHANGES
Alterations in color
Example:
Laxative- phenolphthalein is colorless in acid solution but purple in alkaline mixtures
Classification of Chemical Incompatibilities
G. EXPLOSIVE COMBINATION
Oxidizing agents are chemically incompatible with reducing agents (redox reactions)
Serious explosion may result from certain combinations

H. CEMENTATION
All part of the ingredients of a Rx may set mass of cement-like-hardness.
Occurs when compounds from:
-Hydrates(ex. Plaster of paris) polymerize,
-convert to new crystal forms
Classification of Chemical Incompatibilities
I. SEPARATION OF IMMISCIBLE LIQUIDS
- Immiscible liquids not soluble in the Rx
example: Chloral hydrate may separate as a layer of insoluble chloral
alcoholate in vehicles containing10-50% alcohol and large
amount of certain soluble salts.

J. GELATINIZATION
- Solutions form a gel when combined with certain substances rarely
encountered
Classification of Chemical Incompatibilities
K. DEVELOPMENT OF HEAT OR COLD
- Chemical reactions with either liberation or absorption of considerable amounts of heat
- Chemical reactions taking place spontaneously at room temperature do so with evolution of
heat
• Compounds formed with evolution of heat tend to decomposed when the temperature is raised
• Compounds requiring heat for their formation are more stable at higher temperature

L. HYDROLYTIC CHANGES
- Many substances hydrolyze in water and the change may be hastened by heat, catalyst, esters,
amides, certain metals (Zn, Fe)
Classification of Chemical Incompatibilities
M. INVISIBLE CHANGES
- Chemical changes occur without visible evidence of the reaction.

N. DEVELOPMENT OF POISONOUS SUBSTANCES

- Chemical reaction between two substances producing products which more
toxic than the original substances.
example: KI + Hg2Cl2 (calomel) in the presence of moisture Hg+2 (toxic)
Classification of Chemical Incompatibilities
O. IMPLOSION
Weak bottles having thin spots or flaws may break inwardly due to the
development of a slight vacuum.
• Bottles of syrup were broken by implosion due to removal of oxygen
from the air in the bottle by oxidation of syrup