INCOMPATIBILITIES

DRUG INCOMPATIBILITY- Problem that may arise when two or more drugs are combined during compounding, dispensing, or administration; leads to changes in chemical,
physical and therapeutic properties.
PHYSICAL (PHARMACEUTCAL) INCOMPABILITIES
Interaction between two or more substances which leads to changes in color, odor, taste viscosity and morphology
TYPE DESCRIPTION/MANIFESTATION EXAMPLE REMEDY
1. LIQUEFACTION - Change from solid to liquid form - Store and dispense in tight
- Due to: Hygroscopic- SILICA GEL containers
HYGROSCOPY (absorbs water) Deliquescent- NaCl - Substitute anhydrous form
DELIQUESCENCE (absorbs water & liquefies) Efflorescent- citric acid, atropine, Ferrous - Add adsorbent
EFFLORESCENCE (release of water of sulfate, Alum - Place product in a low humidity
hydration/crystallization) Eutectic mixture- Menthol, Phenol, environment
EUTECTIA (lowering of melting point of mixtures) Thymol, Camphor - Separate and protect potential
eutectic mixtures
- Use of special papers that do no
readily absorb water
Wax paper > vegetable parchment
>
Glassine > bond paper
2. POLYMORPHISM Ability of a drug to exist as two or more crystalline phases - Cocoa butter (alpha- lowest melting - Be familiar with polymorphic drugs/
with different arrangements and/or conformations which point; B- intermediate; B- highest) excipients
have different melting points, solubility - Aspirin
- Chloramphenicol
- Sulfanilamide
3. INCOMPLETE - Two ore more substances which are not homogenous - Oils immiscible in water - Know the drugs solubility
SOLUTION when mixed together; due to insolubility and/or - Gums insoluble in alcohol - Use the salt/ester firm
immiscibility - Resins insoluble in water - Calculate/know the drugs critical
- Alkaloids insoluble in water pH
4. PRECIPITATION - Solute is thrown out of the solution - Aromatic water and salts - Add solubilizers
- aka Salting Out - Digoxin. Diazepam injections + aq IV - Add co-solvents
- Factors: pH, temperature, solvent solution
- Note: physical precipitation- no formation of new - Dibasic Calcium Phosphate in
substances parenteral solutions (warm temp
causes precipitation)
5. SORPTION - General term for surface phenomena of drugs onto - Insulin onto PVC plastics - Check literature
containers, closures, IV tubings, filters, administration - Shorten contact time
devices, etc.
6. VAPORIZATION - Conversion of a volatile substance in to a vapor or - Nitroglycerin - Use of appropriate containers [tight
gaseous condition - Ketones (prevent escape of gas/moisture) or
- Aldehydes hermetic (impervious to air)]
- Alcohol - Addition of macromolecules
- Esters stabilizes volatility of drugs
7. LOSS OF WATER - Removal of water from a drug molecule/ drug product - - Store in tight containers
- Drug can lose crystinallinity, become pasty/liquefy, - Store under correct conditions
crack/crumble, or cake (suspensions) - Add humectants
- Emulsions: o/w to w/o
- Increased concentration of suspensions and solution
 CHEMICAL INCOMPABILITIES
Reaction between 2 or more substances which lead to change in chemical properties of pharmaceutical dosage form
TYPE DESCRIPTION/MANIFESTATION EXAMPLE REMEDY
1. OXIDATION - OXIDATION OXIDATION - Protect from oxygen
REDUCTION - Loss of electrons/ increase in oxidation state Fats and oils Rancidity - Protect from light
- Autooxidation: reaction of drug material with Vitamin C Brown - Add antioxidants
molecular oxygen Epinephrine Pink - Add chelating agents
- Due to: - Control pH
o Presence of oxygen REDUCTION - Keep oxidizing and reducing agents
o Light Silver nitrate silver away from each other
o Heavy metal ions
o Temperature
o pH
o Presence of oxidizing agents
- Dehydrogenation exist to detect due to change in
color

REDUCTION
- Gains of electrons
- Oxidizing agents
- Hydrogenation
- Decrease in oxidation state
2. HYDROLYSIS - Splitting by water Lactams (Penicillins, Cephalosporins) - Store in tight containers
- Most common type of incompatibility Esters (Cocaine, physostigmine, aspirin, - Add desiccants
- Most common mechanism of drug degredation tetracaine, Procaine, Methyldopa) - Control pH
- When water is used as solvent Amides (Dibucaine) - Check literature
- Breaking of bonds Imines (Diazepam) - Refrigerator
3. PHOTOLYSIS - Degradation caused by light - Nifedipine - Storage in colored glass container
(PHOTOOXIDATION) - Cleavage of covalent bonds catalyzed by UV radiation - Nitroprusside (amber for UV and IR, yellow for UV)
from light - Riboflavin - Aluminum foil wraps, blister packs,
- Manifest as change in appearance, such as discoloration - Adriamycine tablet coating
or formation of precipitate - Cisplatin
- Amphotericin B
4. RACEMIZATION - Conversion of one enantiomerically pure mixture to a - L- epinephrine D-epinephrine (15-20x - Storage in light-resistant containers,
racemate less active) addition of buffers to maintain
- From optically active compound to an optically inactive - Local anesthetics stability
mixture
- Equal amounts of dextro (+) and levo (-) isomers
5. EPIMERIZATION - Formation of epimers - Tetracycline - Check literature
- Compound that contains two or moral chiral centers - Pilocarpine
- Changing of one epimeric form into another
6. GELITINIZATION - Gel formation Acacia + Iron salts
7. CEMENTATION - Cake formation Acacia + Bismuth salts
8. EXPLOSIVE MIXTURE - strong RA+ Strong OS KMnO4 + Sugar/ Glycerin
9. PRECIPITATION - New compound Ca(OH)2 + CO2 CaCO3 + H2O
10. EFFERVESCENCE - Evolution of gas Effervescent tablets (NaHCO3 +
tartaric/citric acid)