INCOMPATIBILITIES

PHARMACEUTICAL CARE 4

INCOMPATIBILITIES
- Inability of a substance to maintain its identity or to exercise its inherent properties when brought into
contact with or into the sphere of influence of another substance or a physical force.

-Two classes (from viewpoint of compounder):

(1) Desirable
(2) Undesirable

INCOMPATIBILITIES
when problems arise during:
-compounding
- dispensing
- administration of pharmaceuticals
problems develop as a result of:
- using two or more drugs
- use of only one drug such as dosage errors

classes of incompatibilities
Three classes (based on cause and manifestations):
(1) Physical incompatibilities
physical or chemical interaction between 2 or more ingredients that lead to a visibly recognizable
change
(2) Chemical incompatibilities
involves a reaction in which change is not visible
(3) Therapeutic incompatibilities
involves an undesirable interaction between 2 or more ingredients

The ff. are essential from a theoretical as well as practical viewpoint:

Solubility
Chemical reactivity
Drug stability
Therapeutic activity
Consequences of incompatibility
Patient:
-may not receive the full therapeutic effect of the medication
-adverse effect due to the formation of toxic
products
Physical incompatibilities
Physical stability
is the assurance that the product retains its original physical properties, including appearance,
palatability, uniformity, dissolution and suspendability, during its shelf-life.
I. PHYSICAL INCOMPATIBILITY
Result of:
insolubility (most frequent cause),
liquefaction, or
physical complexation

CLASSIFICATIONS OF PHYSICAL
INCOMPATIBILITY
A. INCOMPLETE SOLUTION (INSOLUBILITY)
When two or more substances are combined, they do not give a homogenous product
- due to immiscibility or insolubility
Examples:
* Silicones are immiscible with water
* Gums are insoluble in alcohol
* Resins are insoluble in water
I. CONCERNS REGARDING INCOMPLETE SOLUTION
1. Sometimes, physician may prescribe the wrong
or insufficient solvent or vehicle.
2. 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:
* for undissolved material, if not beneficial or objectionable, remove it by filtration.
* For doubtful cases: physician should be advised & an
approval should be secured before radical steps are taken.
A. INCOMPLETE SOLUTION
Rx 1
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 is replaced by alcohol, or an isoalcoholic elixir (40%) may be used as solvent.
for low potency drug - suspended with acacia, tragacanth or methocel and dispensed with a shake well
label.
A. INCOMPLETE SOLUTION
Rx 2
Phenobarbital …………………………. 250 mg
Elixir Phenobarbital, q.s…………… 30 mL
M. Sol.
Sig. Teaspoonful at bedtime.
excess of Phenobarbital (controls seizures) is no longer soluble in the elixir.
Remedy:
approximately 10 mL of elixir will be replaced with alcohol to give a clear solution.
Then add 40 mg more of Phenobarbital as a solid so as to obtain the Phenobarbital potency prescribed
CLASSIFICATIONS OF PHYSICAL INCOMPATIBILITY
B. PRECIPITATION
Results when:
- a substance in one solvent is soluble but insoluble
to another solvent that is 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.
Examples:
*Camphor & volatile oils - “salted out” of aromatic waters when salts or metals are
dissolved in the liquid.
* Boric acid is precipitated from a solution when
tragacanth is dissolved in the liquid.
* Colloidal solutions show precipitation on the
addition of electrolytes.
B. PRECIPITATION
Rx 3
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:
Dissolving the bromide in a minimum amount of purified water prior to the addition of the
camphor water eliminates the incompatibility.
B. PRECIPITATION
Rx 4
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 are soluble
only in high alcoholic vehicles.
Remedy:
change in solvent system to avoid precipitation.
add the tincture with rapid stirring to yield a fine colloidal dispersion so 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
SEPARATION OF IMMISCIBLE LIQUIDS
Rx
Chloral hydrate ………………………… 15.00 g
Sodium bromide ………………………. 11.25 g
Elixir Aromatic, qs 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 be informed
D. LIQUEFACTION OF SOLID INGREDIENTS
Mixture of solids sometimes liquefy due to:
- formation of eutectic mixtures
- liberation of water of hydration
LIQUEFACTION OF SOLID INGRDIENTS
Rx
Aminopyrine …………………… 0.3 g
Codeine Sulfate ……………… 15.0 mg
Belladonna Extract ………… 10.0 mg
Acetylsalicylic acid ………… 0.2 g
M. Ft. caps. No. 1 DTD No. 12
liquefies & becomes green within a few days
liquefaction due to a eutectic mixture formed by aminopyrine & ASA
intensification of the green color of the extract as it becomes wet.
REMEDY:
changes avoided - by incorporating one grain of light MgO
or MgCO3 in each capsule
LIQUEFACTION OF SOLID INGRDIENTS
Rx (continuation)
Aminopyrine …………………… 0.3 g
Codeine Sulfate ……………… 15.0 mg
Belladonna Extract ………… 10.0 mg
Acetylsalicylic acid ………… 0.2 g
M. Ft. caps. No. 1 DTD No. 12
REMEDY:
diluents - divided between the reacting ingredients. These are combined with gentle trituration & the
remainder of the ingredients are then incorporated.
another method of filling – allow the liquefaction to take place & then absorb the liquid on sufficient
kaolin or MgCO3 to give a suitable capsule fill
Rx is triturated until homogeneous then encapsuled & placed in tightly stoppered containers.
LIQUEFACTION OF SOLID INGRDIENTS
Rx
Camphor monobromate …………. gr. ss
Menthol …………………………………… gr. ss
Chloral hydrate ……………….……… gr. II
M. One cap. No. 12
eutectic mixture formation – will liquefy – dispense separately or add adsorbent before mixing
CLASSIFICATIONS OF PHYSICAL
INCOMPATIBILITY
E. INCORRECT FORM PRESCRIBED
Physician may prescribe:
- an incorrect form for the most efficient
preparation of the Rx
Example:
*Alkaloid salt to be dissolved in liquid petrolatum
Free alkaloid should be prescribed
- soluble in liquid petrolatum & the
Alkaloidal salts
- insoluble in this solvent.
Answer the following:
1. Results when a substance in one solvent is soluble but insoluble to another solvent that is added to
the solution.
A. Precipitation B. Liquefaction
2. When two or more substances are combined, they do not give a homogenous product due to
immiscibility or insolubility
A. Precipitation B. Incomplete Solution
Answer the following:
3. Rx
Camphor monobromate …………. gr. ss
Menthol …………………………………… gr. ss
Chloral hydrate ……………….……… gr. II
M. One cap. No. 12
This prescription manifests __________
A. Liquefaction B. Separation of Immiscible Liquid
II. CHEMICAL INCOMPATIBILITIES
Occur as a result of:
- chemical interaction among the ingredients
of a Rx.
“Incompatible mixtures should not be dispensed without correction, unless so intended by the
physician.”
CHEMICAL INCOMPATIBILITIES
IMMEDIATE INCOMPATIBILITY
Occurs instantaneously upon compounding.
Readily apparent due to:
- effervescence
- precipitation
- color changes
DELAYED INCOMPATIBILITIES
Other mixtures:
react on such a slow rate that occurs have been termed.
Occur without appreciable visible change/immediate physical evidence of change.
May or may not result in loss of therapeutic activity.
Rx is dispensed if used up before about 10% of the therapeutic activity is lost.
REMEDY:
Use of “Store in a Refrigerator” label
- help decrease the rate of loss of activity
- slows down hydrolysis, redox, or other chemical
reactions (occur more rapidly at rm temp)
Use of“Shake well” label
- when applicable to promote uniform dosage
But when it results to a potentially dangerous product
it should not be dispensed & the physician should be consulted.
CHEMICAL INCOMPATIBILITIES
To generalize:
Ingredients with chemically similar active groups are usually compatible while with different active
groups will sometimes react.
Drugs react like other organic & inorganic compounds.
* reactions manifest through:
- formation of precipitate
evolution of gas
addition or elimination of water
absorption or evolution of heat
formation of complexes or chelated.
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
A. OXIDATION
It is a problem with:
stock solutions, inadequately formulated manufactured products and certain Rx mixture which may
oxidize if exposed to:

air excessive storage

temps. Light
overdilution incorrect pH adjustment
presence of catalysts.
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
OXIDATION
There are substances that Undergo auto-oxidation (chain reaction type of oxidation):
*oils & fats, phenolic substances, aldehydes &
vitamins - used as antioxidants themselves
REMEDY:
* reaction is controlled by the addition of still more reactive inhibitors to:
- provide electrons &
- receive the excess energy possessed by the
activated molecules.
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
B. REDUCTION
Less common in Rxs although:
- silver, mercury, and gold salts may be reduced
by light to the metallic form
C. RACEMIZATION
Conversion of an optically active form to an optically inactive form without changing chemical
constitution.
produces reduced pharmacological activity.
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
D. PRECIPITATION
When two or more pharmaceuticals are combined
- there is the formation of an insoluble substance which precipitates from the solution.
* Flocculent precipitates:
- develop several days after a stock solution or Rx is
prepared due to delayed incompatibilities.
- there are evidences of yeasts, molds or bacterial growth due to an indirect chemical incompatibility
where in the preservative system is inactivated by a
chemical reaction.
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
E. EVOLUTION OF GAS
Formed by chem. reaction between ingredients.
Example:
Effervescence caused by the liberation of CO2 from the: - reaction of carbonates & acids in aqueous
media,
- decomposition of syrups of paraaminosalicylic acid.
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
F. COLOR CHANGES
Alterations in color
Example
Laxative - phenolphthalein is colorless in acid solution but purple in alkaline mixtures

G. EXPLOSIVE COMBINATION
Oxidizing agents are chemically incompatible with reducing agents (redox reactions)
serious explosions may result from certain combinations
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
H. CEMENTATION
All or part of the ingredients of a Rx may set a mass of cement-like hardness.
Occurs when compounds from:
- hydrates (ex. Plaster of paris) polymerize, or convert to new crystal forms.

I. SEPARATION OF IMMISCIBLE LIQUIDS

Immiscible liquids not soluble in the Rx
J. GELATINIZATION
Solutions form a gel when combined with certain substances.
This is rarely encountered.
Example:
*acacia solutions are gelatinized by ferric salt since acacia possesses carboxyl groups which may be
cross-lined by trivalent ferric ions to form polymer chains.
*Collodion is gelatinized by phenol (related to bonding reaction).

K. DEVELOPMENT OF HEAT OR COLD

Chemical reactions with either liberation or absorption of considerable amounts of heat.
Chem. reactions taking place spontaneously at rm. temp. do so with the evolution of heat.
* compounds that are formed with evolution of heat tend to decompose when the temp. is raised.
* compounds that require heat for their formation are more stable at higher temp.
L. HYDROLYTIC CHANGES
Many substances hydrolyze in water & the change may be hastened by heat, catalyst, esters, amides,
certain metals (Zn, Fe), etc.
A. Ionic hydrolysis
ionized species + H+ or OH- of H2O → unionized
insoluble product.
special type of acid-base reaction (change of pH).
Manifested as precipitate of basic salts or hydrolysis
Ex. ZnCl2 + H2O → ZnOHCl + H+
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
HYDROLYTIC CHANGES
B. Molecular hydrolysis
– slower rate than ionic
- reduced therapeutic activity
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
N. INVISIBLE CHANGES
chem. changes occur without visible evidence of the reaction.
There are changes that destroy or change the therapeutic effect of the drug.

O. DEVELOPMENT OF POISONOUS SUBSTANCES

Chem. reaction between two substances produces products which are more toxic than the original
substances.
Ex. KI + Hg2Cl2 (calomel) in the presence of
moisture → Hg+2 (toxic)
CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
P. IMPLOSION
Weak bottles having thin spots or flaws may break inwardly due to the development of a slight vacuum
* Bottles of a syrup were broken by implosion due to removal of oxygen from the air in the bottle by
oxidation of syrup.

OTHER TYPES OF CHEMICAL CHANGE

Incompatibilities such a polymerization, double decomposition, substitution, addition, etc.
Answer the following:
4. This is conversion of an optically active form to an optically inactive form without changing chemical
constitution.
A. Racemization B. Explosion
5. Laxative -phenolphthalein is colorless in acid solution but purple in alkaline mixtures
shows what type of chemical incompatibility?
A. Gelatinization B. Color Changes
Answer the following:
6. Oxidizing + Reducinng Agents
A. Explosion B. Evolution of Gas
7. Plaster of Paris
A. Development of Poisonous substance
B. Cementation
III. THERAPEUTIC INCOMPATIBILITIES
Occur:
When two or more drugs, IV fluids or both are administered together to produce a response which
differs in nature or intensity from that which was intended.
It may occur at the site of the drug action.
THERAPEUTIC INCOMPATIBILITIES
CONSEQUENCES:
Therapeutic effectiveness is reduced or delayed (physical or chem. reaction)
Loss of activity (hydrolysis/oxidation)
delay in the release or absorption of drug (Complexation or combination of drugs with proteins, tannins,
surfactants & other large molecules)

Factors affecting IV compatibility

-pH – incompatibility is more likely to occur when the components of an IV solution differ significantly in
pH. Explained by chemical reaction between an acid and a base, which yields a salt and water; the salt
may form an insoluble ppt.
-Temperature – increased storage temperature speeds up drug degradation. To preserve drug stability,
drugs should be stored in a refrigerator or freezer as appropriate.
-Degree of dilution – generally, the more diluted the drugs are in a solution, the less chance there is for
an ion interaction leading to incompatibility.
DRUG INTERACTIONS
Frequently applied to those situations where the:
effects of one drug are altered by the prior or concurrent administration of another
dietary item influences the activity of a drug (e.g., cheese & monoamine oxidase inhibitors)
drug causes alterations of laboratory test values
drug essentially interacts with itself (e.g. by stimulating its own metabolism)

Mechanisms of drug interaction:

1. DI at the site of absorption – tetracycline (antacids/dairy products); enteric coated (antacid)
2. DI at the site of distribution – warfarin
3. DI at the site of excretion –
probenecid/penicillin
4. Drug biotransformation
DRUG INTERACTIONS
MAY EITHER BE:
A. Adverse drug interaction
B. Beneficial Drug Interaction
Occurs when the action of a prescribed drug is:
- Potentiated, inhibited or otherwise modified in the patient by an interactant so that an
unfavorable response to the drug is elicited.

Causes of ADR
Pharmaceutical causes – altering the quantity of drug available for systemic absorption; influencing
release rates.
Systemic availability of drug influenced by:
particle size, nature and quantity of excipients and coating materials.
Causes of ADR:
Pharmacokinetic causes – the way a drug is handled by the body during ADME may affect humans in as
adverse manner; ototoxicity with aminoglycosides when used in patients with renal failure.
Pharmacodynamic causes – increased sensitivity of target organs in the body to drugs.
Predisposing/Influencing Factors in ADR
 Patient-related factors
 previous ADR or drug allergy
 Sex
 Age
 genetic influence
 miscellaneous ( diet, smoking, alcohol, environmental exposures).
 Presence of renal, hepatic and cardiac diseases.
 Drug-related
 Pharmaceutical properties
 Pharmacokinetic properties
 Pharmacodynamic effects
MULTIPLE DRUG THERAPY IS JUSTIFIED IF IT PROVIDES:
Greater efficacy than can be achieved with full doses of single drugs
Greater margin of safety
More satisfactory onset or duration of effect.
Reasons for increased evidence of drug interactions:
Drug potency
Patients see several physicians
Concurrent use of Rx & non-Rx drugs
Patient’s non-compliance
Drug abuse
CORRECTION OF INCOMPATIBILITIES
consult the physician
use pharmaceutical knowledge
add an ingredient
remove an ingredient
change the vehicle
change an ingredient
change the dosage form
read the literature
CORRECTION OF INCOMPATIBILITIES
Consult the Physician
For the method used on the Rx:
- discuss the matter with prescriber & co-workers.

Examples of acceptable corrections:

Use of modified mixing order.
Dispensing with a “shake well” label.
Making a suspension or emulsification with official agents.
Use of the most appropriate form of the drug for the vehicle prescribed.
Addition of inert ingredients such as diluents, stabilizers, buffers, stiffening agents, preservatives .
other procedures where no therapeutically important change is made in the dosage or ingredients of
the formula.

CORRECTION OF INCOMPATIBILITIES
Procedure requiring approval of the physician:
Addition of materials requiring a change in the dose.
Addition of unofficial suspending agents, emulsifiers, chelating agents or other materials which may
adversely affect the stability of the product.
Omission of troublesome ingredients having little therapeutic activity.
Filtering out inactive sediments,
Dispensing a troublesome ingredient separately,
Changing a brand from that specified,
Changing the dosage forms, i.e., substituting capsules for powders, pills, tablet, triturates, etc.
Other important changes.
CORRECTION OF INCOMPATIBILITIES
Use Pharmaceutical Knowledge
In correcting the problems, the following procedures should be considered first:
Modify the mixing order
Dispense with a “shake well” label
Dispense with a “store in a refrigerator” label
Complete the reaction before packing
Protect from air, light & moisture
CORRECTION OF INCOMPATIBILITIES
Add an Ingredient
Suspending agents
Emulsifying agents
Inert solubilizing or miscibility-increasing ingredients
Diluents
Stiffening or softening agents
CORRECTION OF INCOMPATIBILITIES
Remove an Ingredient
Discard the inactive sediment
Separate the two prescriptions
Change the Vehicle
Increase the volume of mixture & increase dose
Decrease volume of mixture & decrease dose
Change solvent & use the same dose
Change an Ingredient
Use the most soluble form
Use the most stable form
Change the Dosage Form
Use a more suitable dosage form
Use a different brand
Read the literature

Preventing or minimizing incompatibilities

Each drug should be mixed thoroughly after it is added to the preparation.
Solutions should be administered promptly after they are mixed to minimize the time available for a
potential reaction to occur.
The number of drugs mixed together in an IV solution should be kept to a minimum.
If a Rx calls for unfamiliar drugs or IV fluids, compatibility references should be consulted
Drugs.com - to check for drug incompatibilities
Answer the following:
Classify the following:
A. Change the Vehicle
B. Change an Ingredient
C. Remove an Ingredient
9. Discard the inactive sediment
10. Increase the volume of mixture and increase dose
EXAMPLES OF INCOMPATIBILITIES
Insolubility
Rx 1
Potassium iodide ……………….30.0 g
Phenobarbital ……………………… 1.0 g
Thiamine HCl Elixir, q.s. ad…… 240.0 mL
M. Ft. Sol.
alcoholic conc. of the elixir is not sufficient to dissolve the Phenobarbital or to maintain it in solution
a suspension might be prepared but because of the potency of the Phenobarbital & the danger involved
if the patient did not uniformly disperse this drug before taking a dose, dissolution is preferable
Insolubility
Rx (continuation)
Potassium iodide ……………….30.0 g
Phenobarbital ……………………… 1.0 g
Thiamine HCl Elixir, q.s. ad…… 240.0 mL
M. Ft. Sol.
conc of alcohol required to maintain this amount of Phenobarbital in solution is about 27%.
knowledge of alcoholic conc of the elixir would permit calculation of the amount of alcohol that must be
added
Insolubility
Rx (continuation)
Potassium iodide ……………….30.0 g
Phenobarbital ……………………… 1.0 g
Thiamine HCl Elixir, q.s. ad…… 240.0 mL
M. Ft. Sol.
the Phenobarbital is dissolved in this alcohol; the thiamine lost be replaced of the elixir and the
potassium iodide dissolved in the elixir, and the two solutions are mixed.
Sodium Phenobarbital could not be substituted in this system because the acidity of the elixir will
precipitate free Phenobarbital and the alkalinity of the sodium Phenobarbital may cause some
hydrolysis of the thiamine
Insolubility
Rx 2
Ephedrine sulfate ………………………………………..0.25 g
Menthol ……………………………………………………… 0.02 g
Mineral oil, light, q.s. ……………………………… 30.0 mL
M. Ft. Sol.
Alkaloidal salt is not oil-soluble
Substitution of an anhydrous ephedrine base will permit preparation of a clear solution

Insolubility
Rx 3
Peru Balsam ………………………………….2.0 g
Petrolatum, q.s. ………………………… 30.0 mL
M. Ft. Oint.
granular ointment results because the semipolar (phenolic) components of the balsam are not miscible
with the completely non-polar base
Insolubility
Rx (continuation)
Peru Balsam ………………………………….2.0 g
Petrolatum, q.s. ………………………… 30.0 mL
M. Ft. Oint.
compounds possessing the proper balance of polar & non-polar groups, so that they can associate with
both the petrolatum & the balsam, will permit the preparation of a smooth product. Castor oil will serve
this function.
if balsam is first mixed with about an equal amount of castor oil and this mixture incorporated into the
petrolatum, a smooth ointment results.
Insolubility
Rx 4
Magnesium carbonate ……………………………….7.5 g
Sodium bicarbonate …………………………………. 15.0 g
Citric acid …………………………………………………. 15.0 g
Purified water, q.s. ad ……………………………… 500.0 mL
M. Ft. Sol
final appearance of this Rx depends on the order of mixing
if NaHCO3 is added to a solution of the citric acid, and the MgCO3 is added last, the solution will be
incomplete.
Insolubility
Rx (continuation)
Magnesium carbonate ……………………………….7.5 g
Sodium bicarbonate …………………………………. 15.0 g
Citric acid …………………………………………………. 15.0 g
Purified water, q.s. ad ……………………………… 500.0 mL
M. Ft. Sol
if MgCO3 is added to the solution of citric acid first, soluble Mg citrate will be formed
NaHCO3 will be soluble in this mixture and a clear solution will be obtained.
Insolubility
Rx 5
Tr. Benzoin Compound …………………………. 5.0 mL
Glycerin ………………………………………………… 15.0 mL
Rose water, q.s. ad ……………………………….. 100.0 mL
 M. Ft. Lotion.
resins & ether components of the tincture are soluble only in high alcoholic vehicles
change in solvent system results in an unavoidable precipitate
Insolubility
Rx (continuation)
Tr. Benzoin Compound …………………………. 5.0 mL
Glycerin ………………………………………………… 15.0 mL
Rose water, q.s. ad ……………………………….. 100.0 mL
M. Ft. Lotion.
addition of the tincture with rapid stirring yields a fine colloidal dispersion
no suspending agent is necessary
Physical Complexation
Rx 5
Phenol …………………………………. 1.0 g
Polyethylene glycol – 400 ……… 10.0 mL
ZnO …………………………………….. 15.0 g
Purified water, q.s. ad ……………………. 100.0 mL
M. Ft. Lotion.
Complexation of the phenol with the ether oxygens of the PEG – 400 will produce an unsatisfactory
suspension, as well as inactivate the phenol
Substitution of bentonite magma for PEG will permit preparation of a satisfactory product
Oxidation – Reduction
Rx 6
Sodium Salicylate ………………………………….. 8.0 g
Sodium Bicarbonate ……………………………… 16.0 g
Peppermint water, q.s. ad …………………….. 180.0 mL
M. Ft. Sol.
solution darkens on standing
change attributed to the alkaline catalyzed oxidation of the salicylate to a quinoid form
number of substances are useful as antioxidants in retarding the color development and, in this formula,
0.1% sodium bisulfite serves this purpose.
Acid – Base Reactions
Rx 7
Cocaine HCl ………………………….. 0.3 g
Boric acid …..
aa …………………….. 1.2 g
Sodium borate
Purified water, q.s. ad …………. 60.0 mL
Alkalinity imparted to the solution by the sodium borate causes precipitation of the water-insoluble
cocaine base. Elimination of the sodium borate prevents this incompatibility.
This reaction is typical of most amine salts in the presence of bases or basic salts
Acid – Base Reactions
Rx 8
Sodium bicarbonate ….
aa ………………………….. 4.0 g
Bismuth subnitrate
Water, q.s. ad …………………………………………. 90.0 mL
M. Ft. susp.
hydrolysis of the bismuth subnitrate yields nitric acid, which reacts with the bicarbonate to yield CO2.
gas formed would be sufficient to rupture the container
Acid – Base Reaction
Rx (continuation)
Sodium bicarbonate ….
aa ………………………….. 4.0 g
Bismuth subnitrate
Water, q.s. ad …………………………………………. 90.0 mL
M. Ft. susp.
completion of the reaction prior to dispensing is not feasible because of the slow rate of acid production
from the hydrolysis
a satisfactory remedy is to replace the subnitrate salt with the subcarbonate
Acid – Base Reactions
Rx 9
Sodium sulfathiazole ……………………………. 0.65 g
Boric acid sol. 2%, q.s. ad. ………………… 15.00 mL
M. Ft. Sol.
acidity of H3BO3 will cause the formation of free sulfathiazole.
the product is for use as ear drops, dispensing of a suspension might be considered
a more suitable procedure is to eliminate the boric acid & dispense a clear solution
Acid – Base Reactions
Rx 10
Sodium salicylate ………………………………. 15.0 g
Elixir Lactated Pepsin, q.s. ad…………… 120.0 mL
M.
acidic vehicle results in the formation and precipitation of salicylic acid
a change to a neutral or alkaline vehicle or the addition of sufficient alcohol to dissolve the salicylic acid
will correct this incompatibility
Hydrolysis Reactions (Ionic)
Rx 11
Zinc sulfate ………………………… 0.03 g
Sodium borate …………………….. 0.12 g
Rose water, q.s. ad …………….. 30.00 mL
M.
formation of & subsequent hydrolysis of zinc borate results in a precipitate
ZnSO4 alone will also hydrolyze gradually to precipitate a basic salt.
use of H3BO3 in place of the Na3BO3 will prevent the hydrolysis of the Zn salts
Hydrolysis Reactions (Molecular)
Rx 12
Sodium salicylate …………………………….. 4.0 g
Phenobarbital sodium ……………………… 0.6 g
Vitamin B Complex Elixir …………………. 240.0 mL
M.
vit. B complex elixir has an acidic pH
alkalinity of the salts causes deterioration of the B vitamins via hydrolysis as well as eventual
precipitation of the acids of these sodium salts.’
dispensing of the salts separately is suggested
Hydrolysis Reactions (Molecular)
Rx 13
Penicillin G sodium ………………………………… 1,000,000 U
Syrup of Cherry, q.s. ad …………………………… 30 mL
M. Ft. Sol.
hydrolysis of the penicillin salt occurs in the acidic medium as well as precipitation of penicillin as the
free acid
neutral vehicle could be employed to slow down the rate of hydrolysis
Combination Reactions
Rx 14
Butyn sulfate …………………………… 0.65 g
Silver nitrate …………………………….. 0.060 g
Distilled water, q.s. ad …………….. 30.0 mL
M. Ft. Sol.
silver & sulfate ions will combine to form insoluble silver sulfate
elimination of one of the compounds is necessary
Combination Reactions
Rx 15
Benzalkonium chloride …………………………..1 : 5000
Amaranth solution to color ………………….
M. Ft. sol. 30 mL
amaranth (Na salt) is an anionic dye and will combine with cationic antibacterial agent to precipitate as
well as inactivate it.
elimination of the amaranth solution is necessary.

E N D