PHYSICAL INCOMPATIBILITY

Result of:
- Insolubility (most frequent cause),
- Liquefaction, or
- Physical complexation
Cause:
- Non-uniform
- Unsightly or unpalatable mixtures
- Possess the potential danger or non-uniform dosage

CLASSIFICATIONS OF PHYSICAL INCOMPATIBILITY

A. INCOMPLETE SOLUTION
- Two or more substances combined not giving a homogenous product
- Due to immiscibility or insolubility
Examples:
- Silicones are immiscible with water
- Gums are insoluble in alcohol
- Resins are insoluble in water
- Sometimes: physician may prescribe the wrong or insufficient solvent or vehicle
- Use of heat
- Usually objectionable (except to make slowly soluble substances dissolve more rapidly)
- Danger of forming a clear solution (at high temp.) but will deposit crystals on cooling.
Remedy:
- Undissolved material (not beneficial or objectionable)
- Remove by filtration
- For doubtful cases: physician should be advised &approval secured before radical steps are taken

Rx
Terpin hydrate .. 3g
Simple syrup, q.s. ad.. 120 mL
M. Sol.
The terpin hydrate (loosens mucus) is insoluble in simple syrup.
Remedy:
Half of the syrup - replaced by alcohol, or isoalcoholic elixir (40%) may be used as solvent low potency
drug -suspended with acacia, tragacanth or methocel and
dispensed with a shake well label.

Rx
Phenobarbital . 250 mg
Elixir Phenobarbital, q.s
30 mL M. Sol. Sig. Teaspoonful at bedtime.
Excess of Phenobarbital (controls seizures) not soluble in the elixir
Remedy:
Approximately 10 mL of elixir - replaced with alcohol to give a clear solution requires 40 mg more of
Phenobarbital as a solid so as to obtain the Phenobarbital potency prescribed
B. PRECIPITATION- A substance in one solvent is soluble but insoluble to another solvent added to the
solution
Examples:
- Resins - precipitated from alcoholic solutions when water is added
- Mucilagenous and albuminous substances & some metallic salts - frequently precipitated from aqueous
solution when alcohol is added
- Many substances - precipitate from a saturated solution when some other substances are dissolved in
the solution
- Camphor & volatile oils -salted out of aromatic waters when salts or metals are dissolved in the liquid.
- Boric acid - precipitated from a solution when tragacanth is dissolved in the liquid.
- Colloidal solutions - show precipitation on the addition of electrolytes.

Rx
Potassium bromide 8.0 g
Camphor water qs ad .. 60 mL
M. Ft. sol.
Camphor is salted out of the saturated camphor water by the electrolyte, which is better able to compete
for the water
Remedy:
Solution of the bromide in a minimum amount of purified water prior to the addition of the camphor
water -eliminates the incompatibility.

Tr. Benzoin Compound 5.0 mL

Glycerin 15.0 mL
Rose Water qs ad .. 100 mL
M. Ft. lotion
Resins and other components of the tincture soluble only in high alcoholic vehicles.
Remedy:
Change in solvent system - avoids precipitation
Addition of the tincture with rapid stirring - yields a fine colloidal dispersion
No suspending agent is necessary

C. SEPARATION OF IMMISCIBLE LIQUIDS

- Oils dissolved in alcohol
- separate on the addition of water.
- Ethyl nitrite spirit with a substantial proportion of potassium citrate - separates & floats as a layer

Rx
Chloral Hydrate.15.00 g
Sodium Bromide 11.25g
Elixir Aromatic q.s. ad..60.00 mL
Mixture of chloral alcoholate, chloral & alcohol is salted out by soluble bromides etc.
Appears as immiscible layer & dangerous if taken as one dose.
Remedy:
Clear solutions are formed above 50% alcohol or below 10% alcohol
Incompatibility is solved by adding either water or alcohol
NaBr Is Insoluble in 50% alcohol
Replace elixir with water & syrup or add sufficient water (about 1 oz)
To dilute the Rx below 10% alcohol.
Physician should informed.

D.