*******************, RPh
INCOMPATIBILITY means..
• Conflict, disagreement, differences in prescription.
• Problem which could arise during the compounding or
dispensing of a prescription.
• Interaction of two or more substances.
• ADVERSE DRUG REACTIONS (ADR) – results when a
problem arise using only a single drug.
1. INTENTIONAL
- an obvious change once compounds are combined
but their therapeutic effect is maintained.
▪ Example : Effervescence
2. NON-INTENTIONAL
- changes which affect the therapeutic value of the
medication.
▪ Example: Na Phenobarbital gr. 6
Lactated Pepsin Elixir qs ad fz.1
1. PHYSICAL INCOMPATIBILTY
- A condition arising in the process due to conflicting physical
properties of the ingredient in a solvent.
2. CHEMICAL INCOMPATIBILTY
- A condition arising from chemical reaction that changes the
original composition of a substance.
3. THERAPEUTIC INCOMPATIBILTY
- A condition arising from conflicting property in the action of
the drug.
• Physical or chemical interaction between two or more
ingredients that leads to a visibly recognizable change.
• Causes non-uniform or non-palatable mixture which may
possess a potential danger.
1. INCOMPLETE SOLUTION
▪ Forms of Incomplete Solution
o INSOLUBILITY – Inability of the solid material to dissolve in a particular
solvent system.
EXAMPLE: * Camphor + Water (Remedy: Change H2O and use alcohol)
* Gum + Alcohol (Remedy: Change alcohol and use H2O)
* Iodine + Water (Remedy: Use solubilizing agent =
KI, Low amount of water needed)
o IMMISCIBILITY- Two or more liquids fail to mix with one another
homogenously.
EXAMPLE: * Cod liver oil + Water
(Remedy: Convert to emulsion, add emulsifying agent)
* 1mL phenol + 10mL water
(Remedy: Add glycerin drop by drop (co-solvent))
2. PRECIPITATION – the solute which is originally dissolved in the solvent
is thrown out of solution; separation of the solute
- A substance is generally precipitated from its solution in one solvent
in which it is insoluble when added to a solution.
o SALTING OUT – concentrated solutions of electrolytes are mixed in
prescription with solutions of non-electrolytes.
- “Salting-out” also occurs w/ liquids aside from solids where
the less soluble component is pushed out of the solution.
EXAMPLE: KBr + Camphor water (Remedy: Dispense separately)
o CHANGE IN SOLVENT SYSTEM
EXAMPLE: NH4Cl + Camphor + Alcohol + Water
(Remedy: Dispense separately)
o CHANGE IN TEMPERATURE (Endothermic/Exothermic Reactions)
• ENDOTHERMIC REACTION – absorbs heat from the surrounding;
increased temperature of the solution increases solubility.
EXAMPLE: NH4Cl+Water (Imp.Reminder: Store in temperature)
• EXOTHERMIC REACTION – gives off heat to the surrounding; the lower
the temperature of the solution; the lower its solubility, except lime water.
EXAMPLE: Lime water is more soluble in cold than in hot water.
o CHANGE IN pH
EXAMPLE: Phenobarbital Na + Syrup of Orange
(Remedy: Change syrup of Ipecac to simple syrup)
3. LIQUEFACTION OF SOLID INGREDIENT – due to deliquescence,
efflorescence, and eutexia.
▪ Deliquescence – absorbs moisture and liquefies (NaCl)
▪ Efflorescence – release of water of crystallization (Citric acid)
▪ Eutexia – liquefaction of solids at room temperature, due to the
lowering of their melting points. Exhibited by ASA, menthol, phenol,
thymol, camphor, salol and other aldehydes and ketones.
EXAMPLE: Lidocaine + Prilocaine → EMLA
* ASA + Thymol (Remedy: Dispense separately)
** NOTE: Eutexia is NOT always to be expected in mixing ECs.
EXAMPLE: Salol: Acetanilide (2:1 liquefies; 1:2 will not)
Salol: MgCO3 (2:1 liquefies; 1:2 will not)
4.VAPORIZATION – AKA ‘volatilization’; liberation of the API.
EXAMPLE:Volatile oils, ketone, esters, NTG, aldehyde, alcohol
5. POLYMORPHISM – existence of one or more crystalline and/or amorphous
form.
EXAMPLE: Cubic: NaCl Tetragonal: Urea
Monoclinic: Sugar Rhombic: Iodine
Triclinic: Boric acid Hexagonal: Iodoform
6.WATER LOSS – manifested by liquid dosage forms; reverse of liquefaction.
EXAMPLE: Emulsion (phase inversion in O/W emulsion)
Crumbling of ointments and creams
(Remedy: add humectant to prevent dryness e.g. Glycerin & sorbitol)
This occurs due to interactions between or among the
ingredients/drugs.
Reactions in which visible change is NOT necessarily
observed.
1. DELAYED CHEMICAL INCOMPATIBILITY
- changes which occur to as light extent or at a very slow rate with no
distinguishable change that occurs. This may result in a loss of therapeutic
activity.
EXAMPLE: NaCl, ZnSO4 = precipitation
(Remedy: change tonicity agent (NaCl) into boric acid)
A. INTENTIONAL – product of reaction is the one that is used.
EX: ZnSO4 + K2S = white lotion (No correction!)
A. UNINTENTIONAL – product of reaction presents a problem.
EX: Ascorbic Acid + NaHCO3 = Neutralization
(Remedy: Change NaHCO3, use an inert diluent)
** Rx with delayed incompatibility may be dispensed if the prescription
will be used up before about 10% of the therapeutic activity is lost.
2. IMMEDIATE CHEMICAL INCOMPATIBILITY
- This occurs immediately upon compounding and usually it is
apparent.
EXAMPLE: Effervescence, precipitation
1. OXIDATION-REDUCTION (REDOX)
o OXIDATION – remember VILEORA → Valence Increase; Loss of Electrons;
Oxidation; Reducing Agent
• Dehydrogenation
• Triggered by oxygen, light metals
• Manifests as change in color
EXAMPLE: Ascorbic Acid = white to yellow ; Epinephrine = yellow to pink
o REDUCTION – remember VDGEROA → Valence Decrease; Gain of
Electrons; Reduction; Oxidizing Agent
• Hydrogenation
EXAMPLE: Tollen’s test – ‘silver mirror image/test’
2. ACID-BASE REACTIONS (General Reaction: A + B → Salt + Water)
o PRECIPITATION – new product is formed
EXAMPLE: Ca(OH)2 + CO2 → CaCO3 + H2O
o EVOLUTION OF GAS – facilitates effervescence
• Effervescence is desired to mask salty and bitter-tasting drugs
• Chemical reaction involved : NaHCO3 + Citric Acid + Tartaric Acid
3. HYDROLYSIS
- the most common type of incompatibility
- it involves water as the solvent
- the most common mechanism of drug degradation
EXAMPLE: Susceptible groups of the following groups:
* Lactams (penicillins, cephalosporins)
* Esters (local anesthetics)
* Amides (local anesthetics)
* Imines (Benzodiazepines, barbiturates)
4. SOLVOLYSIS – interaction of drug with solvent other than water.
5. PHOTOCHEMICAL DEGRADATION (Photooxidation; Photolysis)
• Degradation by light
• Manifests as change in color
EXAMPLE: Nifedipine, Nitroprusside, Riboflavin, Phenothiazines,
Adriamycin, Cisplatin, and Amphotericin B
(Remedy: Store in light-resistant containers)
6. RACEMIZATION – the optically active form of drug is converted into its
enantiomorph, continues until 50% of original drug is converted to its
optically inactive mixture.
• Product: Racemic mixture – contains equal amounts of dextro (+R) and
levo (- L) isomers.
EXAMPLE: Thalidomide (R- for morning sickness; S - teratogenic)
Naproxen (Active form – NSAID; Inactive - Hepatotoxic)
7. GELATINIZATION – gel or gelatin formation
EXAMPLE: Acacia + Ferrous salts
8. CEMENTATION – cake formation
EXAMPLE: Acacia + Bismuth salts
9. EXPLOSIVE MIXTURE – reducing agent (RA) + oxidizing agent (OA)
EXAMPLE: Sugar + KMnO4 ; Glycerin + KMnO4
10. POLYMERIZATION – Formation of 5-OH-methylfurfural from Dextrose
- Also known as Pharmacologic Incompatibility, is a
form of incompatibility whereby the ingredients of the drugs
of antagonistic medicinal activity are prescribed together.
- It usually involves drug to drug interactions, drug to
food interactions, drug and herbal medicines interaction
and drug to laboratory tests interaction.
1. PROPERTIES OF THE DRUG
A. Physical Properties – these are drugs that can cause absorption or
adsorption of drugs
EXAMPLE: Kaopectate suspension + Tetracycline
* TCN can be absorbed by kaolin, hence no TCN is absorbed
B. Chemical Properties – the tendency of the drugs to produce a rxn
EXAMPLE: TCN + Milk = Chelation
C. Toxic Properties – Toxic + Toxic = VERY TOXIC
EXAMPLE: Aminoglycoside + Loop Diuretic = Both ototoxic → more toxic
D. Therapeutic Properties
EXAMPLE: Penicillin + Chloramphenicol = no effect
(bactericidal) + (bacteriostatic)
2. COMBINATION WITH OTHER DRUGS AND EXCIPIENTS
EXAMPLE: Veegum – excipient in antacid suspension that causes drug
interaction with antibiotics.
3. ROUTE AND FREQUENCY OF ADMINISTRATION
EXAMPLE: IV using the same tube for Carbenicillin and Gentamycin
Correction: Change the ROA of one of the drugs.
4. KINETICS OF THE DRUG – ADME
5. DRUG INTERACTIONS - If the drug has the ability to interact with other
drugs, drug interaction or therapeutic inability occurs.
1. IMPROPER DOSES
o Overdosage
• Excessive amounts taken at one time
• Doses repeated at too frequent intervals
• Milligram instead of microgram
• Dose-dumping from modified release formulation
o Underdosage
• Administration of very small doses
• Dosage given at less frequent intervals
• Milligram instead of gram
• Tinctures instead of fluidextracts
2. SYNERGISTIC AND ANTAGONISTIC COMBINATION
* Synergistic – drugs with same pharmacologic action; intentional or
unintentional.
* Antagonistic – drugs with opposing pharmacologic action; may be
acceptable or not.
3. WRONG DRUG
o Trademark error or ineffective generic name – SALADs
o Improperly formulated dosage – physical or chemical incompatibilities
o Dosage form error – ophthalmic ointment instead of topical gel
o Improper dose – Buccal or SL tablets being swallowed.
4. CONTRAINDICATD DRUG
EXAMPLE: Hypertensives – NO to vasoconstrictors
Asthmatics – NO to penicillins
Patients with ulcer – NO to steroids
5. FORMATION OF TOXIC COMPOUNDS – May result from chemical
incompatibility
6. REDUCTION OR DELAY IN THERAPEUTC EFFECTIVENESS
o May be due to chemical reaction or physical change
o Failure to comply instructions for proper storage and administration of
the product.
