PHYSICAL INCOMPATIBILITIES ASSOCIATED WITH • Example

ORAL LIQUID & SOLIDS DOSAGE FORMS o Aspirin

• Physical interaction between two or more o Theobroma
ingredients that leads to a visibly recognizable o Cacao
change o Chloramphenicol
• Usually occurs during compounding. o Sulfanilamide
6. Loss of Water
1. INSOLUBILITY • liquid dosage forms:
• Example: o emulsion: phase inversion in o/w
o gum & alcohol emulsions)
o pectin & alcohol o suspensions & solutions: (increased
o resin & water potency)
o oil & water
2. Precipitation CHEMICAL INCOMPATIBILITIES
• salting out process • reaction in which a visible change is not necessarily
• solute which is originally dissolved in the solvent is observed
thrown out of solution 1. Oxidation
• Example: • loss of electrons
o aromatic water & salt • reducing agents
o spirits & salt solution • dehydrogenation
3. Liquefaction of Solid Ingredient • increase in oxidation state
• Deliquescence - absorbs moisture & dissolves • triggered by oxygen, light, metals
o NaCl • manifests as change in color
• Efflorescence - release of water of crystallization • e.g. ascorbic acid, epinephrine
o citric acid
o atropine S04 2. Reduction
o FeS04 • gain of electrons
o alum • oxidizing agents
• Eutexia - lowering of melting point • hydrogenation
o menthol, phenol,. thymol, camphor • decrease in oxidation state
o REMEDY: addition of inert powder such as • e.g. Tollen's test
magnesium oxide
• Hygroscopic - absorbs moisture but does not 3. Hydrolysis
dissolve • A solvolysis process in which drugs interact with
o silica gel water molecules → breakdown products of
o store in tight, wide mouth jar different chemical composition
4. Vaporization or volatilization o The concentration of the active ingredient
• liberation of the active ingredient decreases
• Example • involving water as solvent
o Nitroglycerine • most common type of incompatibility
o Camphor • most common mechanism of drug degradation
o Menthol • susceptible groups:
o essential oils o β-lactams (penicillins, cephalosporins)
• PREVENTION: → penicilloic acid
o use of heat-sealed plastic bags or o esters (cocaine, physostigmine, aspirin,
o by double wrapping with waxed or glassine tetracaine, procaine, methyldopa)
paper inside white bond paper o amides (dibucaine)
5. Polymorphism o imines (diazepam)
• existence of one or more crystalline and/or 4. Solvolysis
amorphous forms • interaction of drug with solvent other than water
• different polymorphs of a drug solid can have have 5. Racemization
different properties.

PHYSICAL INCOMPATIBILITIES ASSOCIATED WITH ORAL SOLID & LIQUID DOSAGE FORMS 1
• action or process of changing from an optically • cake formation
active compound into a racemic compound or an • example
optically inactive mixture o acacia + bismuth salts
• racemic mixture: equal amounts of dextro (+) & levo 10. Gelatinization
(-) isomers • gel or gelatin formation
• frequently the l-form is more pharmacologically • example
active than the d-counterpart o acacia + iron salts
• The activity of racemic mixture is just over one half 11. Polymerization
that of the l-form. • Example
6. Precipitation o formation of 5-0H-methylfurfural from
• salting out process dextrose
• two or more drugs interacting to form a new 12. Photo-Oxidation/Photolysis
substance • degradation by light
• example • manifests as change in color
o Ca(OH)2 + C02---+ CaC03 + H20 • colored glass containers most commonly are used
7. Evolution of Gas to protect light sensitive formulations
• Effervescence • stabilizers and antioxidant can also be used to
• Example: inhibit photolysis
o effervescent tablet (contains NaHC03 & • Example
tartaric or citric acid) o Nifedipine
o p-amino salicylic acid (PAS) o Nitroprusside
8. Explosive Mixture o Riboflavin
• reducing agent (RA) + oxidizing agent (OA) o Phenothiazines
• example: o Adriamycin
o sugar + KMn04, glycerin + KMn04 o Cisplatin
9. Cementation o amphotericin B

PHYSICAL INCOMPATIBILITIES ASSOCIATED WITH ORAL SOLID & LIQUID DOSAGE FORMS 2