INCOMPATIBILITIES Examples: Examples:

When problems arise during: - Silicones are immiscible with water - Resins - precipitated from alcoholic solutions when water
- Compounding - Gums are insoluble in alcohol is added
- Dispensing - Resins are insoluble in water - Mucilagenous and albuminous substances & some
- Administration of pharmaceuticals - Sometimes: physician may prescribe the wrong or metallic salts - frequently precipitated from aqueous
- Problems develop as a result of: insufficient solvent or vehicle solution when alcohol is added
- Using two or more drugs - Use of heat - Many substances - precipitate from a saturated solution
- Use of only one drug such as dosage errors - Usually objectionable (except to make slowly soluble when some other substances are dissolved in the
substances dissolve more rapidly) solution
TYPES OF INCOMPATIBILITIES - Danger of forming a clear solution (at high temp.) but - Camphor & volatile oils - “salted out” of aromatic waters
- Physical will deposit crystals on cooling. when salts or metals are dissolved in the liquid.
- Chemical - Boric acid - precipitated from a solution when
- Therapeutic Remedy: tragacanth is dissolved in the liquid.
- Combination of types - Undissolved material (not beneficial or objectionable) - Colloidal solutions - show precipitation on the addition of
- Remove by filtration electrolytes.
INCOMPATIBILITIES - For doubtful cases: physician should be advised &
The ff. is essential from a theoretical as well as practical approval secured before radical steps are taken Rx
viewpoint: Potassium bromide …………………… 8.0 g
- Solubility Rx Camphor water qs ad ……………….. 60 mL
- Chemical reactivity Terpin hydrate …………………………….. 3g M. Ft. sol.
- Drug stability Simple syrup, q.s. ad…………………….. 120 mL Camphor is salted out of the saturated camphor water by
- Therapeutic activity M. Sol. the electrolyte, which is better able to compete for the
The terpin hydrate (loosens mucus) is insoluble in simple water
CONSEQUENCES OF INCOMPATIBILITY syrup. Remedy:
Patient: Remedy: Solution of the bromide in a minimum amount of purified
- May not receive the full therapeutic effect of the Half of the syrup - replaced by alcohol, or isoalcoholic elixir water prior to the addition of the camphor water -
medication (40%) may be used as solvent low potency drug - eliminates the incompatibility.
- Adverse effect due to the formation of toxic suspended with acacia, tragacanth or methocel and
products dispensed with a shake well label. Rx
Tr. Benzoin Compound ……………… 5.0 mL
I. PHYSICAL INCOMPATIBILITY Rx Glycerin …………………………………… 15.0 mL
Result of: Phenobarbital …………………………. 250 mg Rose Water qs ad …………………….. 100 mL
- Insolubility (most frequent cause), Elixir Phenobarbital, q.s…………… 30 mL M. Ft. lotion
- Liquefaction, or M. Sol. Resins and other components of the tincture – soluble
- Physical complexation Sig. Teaspoonful at bedtime. only in high alcoholic vehicles.
Excess of Phenobarbital (controls seizures) not soluble in Remedy:
Cause: the elixir Change in solvent system - avoids precipitation
- Non-uniform Remedy: Addition of the tincture with rapid stirring - yields a fine
- Unsightly or unpalatable mixtures Approximately 10 mL of elixir - replaced with alcohol to colloidal dispersion
- Possess the potential danger or non- give a clear solution requires 40 mg more of Phenobarbital No suspending agent is necessary
uniform dosage as a solid so as to obtain the Phenobarbital potency
prescribed C. SEPARATION OF IMMISCIBLE LIQUIDS
CLASSIFICATIONS OF PHYSICAL INCOMPATIBILITY - Oils dissolved in alcohol - separate on the addition of
A. INCOMPLETE SOLUTION B. PRECIPITATION water.
- Two or more substances combined not giving a - A substance in one solvent is soluble but insoluble - Ethyl nitrite spirit with a substantial proportion of
homogenous product to another solvent added to the solution potassium citrate - separates & floats as a layer
- Due to immiscibility or insolubility
Rx Rx
Chloral hydrate ………………………… 15.00 g Camphor monobromate …………. gr. ss
Sodium bromide ………………………. 11.25 g Menthol …………………………………… gr. ss
Elixir Aromatic, qs ad ……………….. 60.00 mL Chloral hydrate ……………….……… gr. II
Mixture of chloral alcoholate, chloral & alcohol is salted M. One cap. No. 12
out by soluble bromides, etc. Eutectic mixture formation – will liquefy – dispense
Appears as immiscible layer & dangerous if taken as one separately or add adsorbent before mixing
dose.
REMEDY: E. INCORRECT FORM PRESCRIBED
Clear solutions are formed - above 50% alcohol or below Physician may prescribe:
10% alcohol - An incorrect form for the most efficient preparation of
Incompatibility is solved by adding either water or alcohol. the Rx
NaBr is insoluble in 50% alcohoL Example:
Replace elixir with water & syrup or add sufficient water - Alkaloid salt to be dissolved in liquid petrolatum
(about 1 oz) to dilute the Rx below 10% alcohol. - Free alkaloid should be prescribed, soluble in liquid
Physician should be informed petrolatum & the
- Alkaloidal salts insoluble in this solvent.
D. LIQUEFACTION OF SOLID INGREDIENTS
Mixture of solids sometimes liquefy due to: II. CHEMICAL INCOMPATIBILITIES
- Formation of eutectic mixtures Occur as a result of:
- Liberation of water of hydration - Chemical interaction among the ingredients of a Rx.
Rx Incompatible mixtures:
Aminopyrine …………………… 0.3 g - Should not be dispensed without correction, unless so
Codeine Sulfate ……………… 15.0 mg intended by the physician
Belladonna Extract ………… 10.0 mg
Acetylsalicylic acid ………… 0.2 g IMMEDIATE INCOMPATIBILITY
M. Ft. caps. No. 1 DTD No. 12 Occurs instantaneously upon compounding
Liquefies & becomes green within a few days Readily apparent due to:
Liquefaction due to a eutectic mixture formed by - Effervescence
aminopyrine & ASA - Precipitation
Green color is intensification of the green color of the - Color changes
extract as it becomes wet.
REMEDY: DELAYED INCOMPATIBILITIES
Changes avoided - by incorporating one grain of light MgO Other mixtures:
or MgCO3 in each capsule - React on such a slow rate that occurs have been termed.
Diluents - divided between the reacting ingredients, these - Occur without appreciable visible change/immediate
combined with gentle trituration & the remainder of the physical evidence of change
ingredients incorporated. - May or may not result in loss of therapeutic activity
Another method of filling – allow the liquefaction to take - Rx is dispensed if used up before about 10% of the
place & then absorb the liquid on sufficient kaolin or therapeutic activity is lost.
MgCO3 to give a suitable capsule fill
Rx is triturated until homogeneous then encapsuled & REMEDY:
placed in tightly stoppered containers. 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
Result of a potentially dangerous product
- Should not be dispensed & the physician be consulted
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
If a high energy system can form a more stable, low energy
system.
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
Problem with:
Stock solutions, inadequately formulated manufactured
products, certain Rx mixture may also oxidize if exposed
to:
Air Excessive storage
Temperatures Light
Overdilution Incorrect pH adjustment
Presence of catalysts.
Undergo auto-oxidation (chain reaction type of
oxidation):
- Oils & fats, phenolic substances, aldehydes &
vitamins - used as antioxidants themselves
REMEDY:
Controlled by addition of still more reactive inhibitors to:
- Provide electrons &
- Receive the excess energy possessed by the activated
molecules
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.
D. PRECIPITATION
Two or more pharmaceuticals are combined
- Formation of an insoluble substance which precipitates
from solution
Flocculent precipitates
- Develop several days after a stock solution or Rx is
prepared
- Due to delayed incompatibilities
- Evidence of the growth of yeasts, molds or bacteria.
- Growth due indirectly to a chemical incompatibility if
the preservative system is inactivated by a chemical
reaction
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
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
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
Ex. Chloral hydrate may separate as a layer of insoluble
chloral alcoholate in vehicles containing 10-50% alcohol &
large amounts of certain soluble salts
J. GELATINIZATION Hydrolysis Reactions (Molecular)
Solutions form a gel when combined with certain Rx
substances rarely encountered Sodium salicylate …………………………….. 4.0 g
Example: Phenobarbital sodium ……………………… 0.6 g
- Acacia solutions are gelatinized by ferric salt since acacia Vitamin B Complex Elixir …………………. 240.0 mL
possesses carboxyl groups which may be cross-lined by M.
trivalent ferric ions to form polymer chains Vit. B complex elixir has an acidic pH
- Collodion is gelatinized by phenol (related bonding Alkalinity of the salts causes deterioration of the B
reaction) vitamins via hydrolysis as well as eventual precipitation of
the acids of these sodium salts.
K. DEVELOPMENT OF HEAT OR COLD Dispensing of the salts separately is suggested
Chemical reactions with either liberation or absorption of
considerable amounts of heat Hydrolysis Reactions (Molecular)
Chem. reactions taking place spontaneously at rm. temp. Rx
do so with evolution of heat Penicillin G sodium ………………………………… 1,000,000 U
- Compounds formed with evolution of heat tend to Syrup of Cherry, q.s. ad …………………………… 30 mL
decompose when the temp. is raised M. Ft. Sol.
- Compounds requiring heat for their formation are more Hydrolysis of the penicillin salt occurs in the acidic medium
stable at higher temp. as well as precipitation of penicillin as the free acid
Neutral vehicle could be employed to slow down the rate
L. HYDROLYTIC CHANGES of hydrolysis
Many substances hydrolyze in water & the change may be
hastened by heat, catalyst, esters, amides, certain metals M. INVISIBLE CHANGES
(Zn, Fe), etc. Chem. changes occur without visible evidence of the
1. Ionic hydrolysis reaction
- Ionized species + H+ or OH- of H2O → unionized insoluble Changes that destroy or change the therapeutic effect
product
- Special type of acid-base reaction (change of pH). N. DEVELOPMENT OF POISONOUS SUBSTANCES
- Manifested as precipitate of basic salts or hydrolysis Chem. reaction between two substances producing
- Ex. ZnCl2 + H2O → ZnOHCl + H+ products which are more toxic than the original
substances
2. Molecular hydrolysis Ex. KI + Hg2Cl2 (calomel) in the presence of moisture →
- Slower rate than ionic Hg+2 (toxic)
- Reduced therapeutic activity
O. IMPLOSION
Hydrolysis Reactions (Ionic) Weak bottles having thin spots or flaws may break
Rx inwardly due to the development of a slight vacuum
Zinc sulfate ………………………… 0.03 g - Bottles of a syrup were broken by implosion due to
Sodium borate …………………….. 0.12 g removal of oxygen from the air in the bottle by oxidation
Rose water, q.s. ad …………….. 30.00 mL of syrup
M.
Formation of & subsequent hydrolysis of zinc borate P. OTHER TYPES OF CHEMICAL CHANGE
results in a precipitate Incompatibilities such a polymerization, double
ZnSO4 alone will also hydrolyze gradually to precipitate a decomposition, substitution, addition, etc.
basic salt.
Use of H3BO3 in place of the Na3BO3 will prevent the
Hydrolysis of the Zn salts
III. THERAPEUTIC INCOMPATIBILITIES
OCCUR:
- When two drugs are administered together to produce a
response which differs in nature or intensity from that
which was intended
- At the site of the drug action
CONSEQUENCES:
- Therapeutic effectiveness 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)
RESPONSIBLE:
- Physician rather than the pharmacist but the pharmacist
may inform the physician to eliminate:
- Errors in Rx writing/interpretation
- Overdose (excessive single dose/too frequent
administration)
- Contraindicated drugs (steroids/peptic ulcer)
- Synergistic/Antagonistic effects
- Alteration of Rx order requires permission of prescriber
DRUG INTERACTIONS
Frequently applied to those situations:
- 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)
- A drug causes alterations of laboratory test values
- A 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:
- Adverse drug interaction
- Beneficial Drug Interaction
I. ADVERSE DRUG INTERACTION
Noxious (lethal), unintended & occurs at doses normally
used in man for prophylaxis or diagnosis or therapy of
disease.
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
Some have been:
- associated with inheritable disorders some of which are
related to race
TYPES OF ADVERSE DRUG REACTIONS:
A. Side effects
Troublesome, secondary pharmacological effects & usually
not very dangerous
Useful in determining when the:
- Effective dose is reached
- May even be beneficial as with the sedative effects of
antihistamine syrups given to children
Minimized & desired activity retained by:
- Reducing the dosage or using the proper combination of
drugs
B. Extension Effects
Excessive pharmacologic actions normally dose-related
Show up in patient given enough drug may develop rapidly
or may produce a delayed toxic effect through
cumulative/increasing build up.
Ex. Cumulative toxic effects which are undesirable
Yellowing of teeth in the young child given tetracycline
Ataxia after chlorpromazine
Hypersensitivity reactions also represent overdose of the
exquisitely sensitive individual given a normal size dose or
due to:
- allergies or other immune reactions (require prior
sensitization)
CLASSIFICATIONS OF ADR
1. Type A (Augmented) – actions related to the
pharmacological activity of the drug
a) Extension effects
- Predictable, dose related responses arising from an
extension of therapeutic effect
- Prevention is adjustment of dosage regimen.
Ex. Benzodiazepines (anxiety neurosis) – sedation
and falls/trauma.
b) Adverse effects
- Predictable, dose dependent reactions unrelated to the
goal of therapy
- Often produced by the same drug-receptor interaction
responsible for the therapeutic effect, differing only in
the tissue/s or organ/s affected.
Ex. Atropine –dryness of the mouth
codeine – constipation
2. Type B (Bizarre)
- Totally abnormal effects, unrelated from the drug’s
known pharmacological actions
- Very small doses of the drug may elicit the reaction once
allergy or idiosyncrasy is established.
Ex. Penicillin hypersensitivity –anaphylaxis; reaction
disappears on discontinuation of the drug.
3. Type C (Continuous)
- Long term effects usually related to the dose and
duration of treatment.
Ex. Ethambutol – optic neuropathy
4. Type D (Delayed)
- Carcinogenesis (hormonal/gene toxicity)
- Adverse effects associated with reproduction
(teratogens)
5. Type E (Ending of use/Withdrawal syndromes)
- Alcohol-delirium tremens (disorientation and visual
hallucinations)
- barbiturates – restlessness, mental confusion,
convulsions
6. Type F (Failure of efficacy)
- Therapeutic failure can sometimes be attributed to a lack
of efficacy of drug products.
- Examples:
- Failure to control infection/ apparent antimicrobial
resistance; uncontrolled hypertension
- Failure of efficacy of the drug can be the result of
imperfect or counterfeit manufacture of the product.
CAUSES OF ADR
1. 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
2. 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.
3. Pharmacodynamic causes – increased sensitivity of
target organs in the body to drugs
PREDISPOSING/INFLUENCING FACTORS IN ADR
Patient-related factors
- Presence of renal, hepatic, and cardiac disease
- Age
- Previous ADR or drug allergy
- Sex
- Genetic influence
- Miscellaneous ( diet, smoking, alcohol, environmental
exposures)
Drug-related factors
- Pharmaceutical properties
- Pharmacokinetic properties
- Pharmacodynamic effects
II. BENEFICIAL DRUG INTERACTION
Desired & intended, when a combination of medications
produces:
- Improved therapy
- Perhaps a greater margin of safety
- More appropriate onset or duration of action
- Lowered toxicity
- Enhanced potency with diminished side effects of drug
may be modified by prior or concurrent administration of
another drug
- Improved therapy is possible by judicious use of
combined medication but
- Serious adverse effects may result from drug interaction
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
CLINICAL FACTORS IN DI Ex. of acceptable corrections:
- Diagnostic errors Use of: modified mixing order
- Prescribing errors - Dispensing with a “shake well” label
- Insufficient study of the patient - Suspension or emulsification with official agents
- Contraindicated drugs - Most appropriate form of the drug for the vehicle
- Excessive single dose prescribed,
- Excessive daily dose - Other procedures where no therapeutically important
- Additive and synergistic combination change is made in the dosage or ingredients of the
- Antagonistic combination formula.
- Rx writing errors
- Nomenclature error Borderline cases (depending on the Rx or
- Dosage form error Relationship between the pharmacist & physician:
- Drug Administration and Patient Care - Addition of inert ingredients such as:
-- placebo and psychosomatic factors diluents, stabilizers, buffers, stiffening agents,
--unpalatability preservatives & other procedures in which the dose or
activity is not altered appreciably
IV. COMBINATION OF FACTORS
More than one error or drug interaction problem may Procedure requiring approval of the physician:
occur in a clinical situation. Addition of materials requiring a charge in the dose
Cause never determined although: Addition of:
- It is the joint responsibility of the physician & pharmacist - Unofficial suspending agents, emulsifiers, chelating
to find the cause & eliminate any further similar agents or other materials which may adversely affect the
situations. stability
- Omission of troublesome ingredients having little
PHARMACIST: therapeutic activity
Use his training to investigate the pharmaceutical aspects: - Filtering out inactive sediments
- Possible drug instability, physical, chemical, therapeutic - Dispensing a troublesome ingredient separately
incompatibilities while cooperating with the physician in - Changing a brand from that specified
exploring clinical aspects (possible drug interactions, - Changing the dosage forms, i.e., substituting capsules for
adverse drug reactions, diagnostic, prescribing or powders, pills, tablet, triturates, etc. and other important
administration errors, etc.) changes.
- Pertinent physical, chemical, pharmacodynamics,
pharmacological & pharmaceutical factors USE PHARMACEUTICAL KNOWLEDGE
In correcting the problems, the following procedures
CORRECTION OF INCOMPATIBILITIES should be considered first:
- Consult the physician - Modify the mixing order
- Use pharmaceutical knowledge - Dispense with a “shake well” label
- Add an ingredient - Dispense with a “store in a refrigerator” label
- Remove an ingredient - Complete the reaction before packing
- Change the vehicle - Protect from air, light & moisture
- Change an ingredient - Add an Ingredient
- Change the dosage form - Suspending agents
- Read the literature - Emulsifying agents
- Consult the Physician - Inert solubilizing or miscibility-increasing ingredients
- Diluents
- Method used on the Rx - Stiffening or softening agents
-- discuss the matter with prescriber & co-workers - 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 AND 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
EXAMPLES OF INCOMPATIBILITIES
INSOLUBILITY
Rx
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
- 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
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
Rx
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
Rx
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
- 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.
Rx
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.
- 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.
Rx
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
- Addition of the tincture with rapid stirring yields a fine
colloidal dispersion
- No suspending agent is necessary
PHYSICAL COMPLEXATION
Rx
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
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
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
Rx Rx
Sodium bicarbonate …. Benzalkonium chloride …………………………..1 : 5000
aa …………………………………………………..……….. 4.0 g Amaranth solution to color ………………….
Bismuth subnitrate M. Ft. sol. 30 mL
Water, q.s. ad …………………………………………. 90.0 mL - Amaranth (Na salt) is an anionic dye and will combine
M. Ft. susp. with cationic antibacterial agent to precipitate as well as
- Hydrolysis of the bismuth subnitrate yields nitric acid, inactivate it.
which reacts with the bicarbonate to yield CO2. - Elimination of the amaranth solution is necessary.
- Gas formed would be sufficient to rupture the container
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

Rx
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

Rx
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

COMBINATION REACTIONS
Rx
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