Physical incompatibility

Physical incompatibility

Incomplete solution

Precipitation

Liquefaction

Polymorphism

Sorption

Volatilization / Vaporization

Loss of water

Chemical Incompatibilities

Redox

Hydrolysis

Acid-base reaction

Racemization

Solvolysis

Explosive mixture

Photooxidative degradation

Gelatinization

Cementation

Physical incompatibility: result, cause

Result of:

• Insolubility (most frequent cause)

• Liquefaction

• Physical complexation

Cause:

• Non-uniform particle size

• Unsightly or unpalatable mixtures - possess potential danger or non-uniform dosage

Incomplete solution

Due to immiscibility or insolubility:

_{^{Immiscibility: liquid-liquid mixture}}

_{^{Insolubility: solid-liquid mixture}}

Due to a wrong solvent:

_{^{Polar ingredients in nonpolar solvent, vice versa}}

Precipitation

Insolubility

Mucilaginous, albuminous substances and some metallic salts

Camphor in camphor water and volatile oils

Boric acid

Colloidal solutions

Electrolytes

Colloidal solutions show precipitation on addition of ‘blank’

Tragacanth

Boric acid is precipitated when ‘blank’ is added in a saturated solution

Alcohol

Mucilaginous, albuminous substances and some metallic salts are precipitated from aqueous solution by the addition of ‘blank’

Separation of immiscible liquids

Oils dissolved in alcohol separate with the addition of water

Spirit of ethyl nitrate + potassium citrate = separation and layering

Liquifaction of solid ingredients (eutexia)

Due to:

Formation of eutectic mixtures

Lowering of meting points, e.g., salol and menthol

Liberation of water of hydration/crystallization

Presence of deliquescence substances

E.g., phenol, thymol, aspirin (ASA)

Incorrect form prescribed

Example: Alkaloid salt to be dissolved in liquid petrolatum

Free alkaloid should be prescribed - _{^{soluble in liquid petrolatum}}

Alkaloidal salts are insoluble in this solvent - _{^{They are only soluble in water}}

Gelatinization

Solution of acacia is gelatinized by the addition of ferric salts

Collodion is gelatinized by phenol

Polymorphism

Ability to exist in several or different crystalline form

Cubic

NaCl

Tetragonal

Urea

Hexagonal

Iodoform

Rhombic

Iodine

Monoclinic

Sucrose

Triclinic

Boric acid

Sorption

Absorption: penetrates the other substance

Adsorption: adheres to the surface of the other substance

Water loss

Ointments: Crumbling

Emulsions: Cracking _{^{(complete separation of layers)}}

Gels: Syneresis _{^{(loss or decrease of water content)}}

REMEDIES OF PHYSICAL INCOMPATIBILITY

Omission of unimportant ingredient of little therapeutic value.

Dispense the ingredients separately

Addition of an inert ingredient to correct the difficulty

Alteration in the solvents used (substituting alcohol or glycerin for water or vv)

Emulsification or suspension

Changing the order of mixing of ingredients

Changing the bulk of preparation

Use of different form of the same ingredient

Addition of stiffening agents as in ointments and suppositories _{^{to retain water}}

Addition of an ingredient which promotes solubility