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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 Result of a potentially dangerous product
Chloral hydrate ………………………… 15.00 g Camphor monobromate …………. gr. ss - Should not be dispensed & the physician be consulted
Sodium bromide ………………………. 11.25 g Menthol …………………………………… gr. ss
Elixir Aromatic, qs ad ……………….. 60.00 mL Chloral hydrate ……………….……… gr. II To generalize:
Mixture of chloral alcoholate, chloral & alcohol is salted M. One cap. No. 12 Ingredients with chemically:
out by soluble bromides, etc. Eutectic mixture formation – will liquefy – dispense - Similar active groups are usually compatible while
Appears as immiscible layer & dangerous if taken as one separately or add adsorbent before mixing - With different active groups will sometimes react
dose.
REMEDY: E. INCORRECT FORM PRESCRIBED Drugs react like other organic & inorganic compounds
Clear solutions are formed - above 50% alcohol or below Physician may prescribe: If a high energy system can form a more stable, low energy
10% alcohol - An incorrect form for the most efficient preparation of system.
Incompatibility is solved by adding either water or alcohol. the Rx Reactions manifest through:
NaBr is insoluble in 50% alcohoL Example: - Formation of precipitate evolution of gas
Replace elixir with water & syrup or add sufficient water - Alkaloid salt to be dissolved in liquid petrolatum - Addition or elimination of water
(about 1 oz) to dilute the Rx below 10% alcohol. - Free alkaloid should be prescribed, soluble in liquid - Absorption or evolution of heat
Physician should be informed petrolatum & the Formation of complexes or chelated
- Alkaloidal salts insoluble in this solvent.
D. LIQUEFACTION OF SOLID INGREDIENTS CLASSIFICATION OF CHEMICAL INCOMPATIBILITIES
Mixture of solids sometimes liquefy due to: II. CHEMICAL INCOMPATIBILITIES A. OXIDATION
- Formation of eutectic mixtures Occur as a result of: Problem with:
- Liberation of water of hydration - Chemical interaction among the ingredients of a Rx. Stock solutions, inadequately formulated manufactured
Rx Incompatible mixtures: products, certain Rx mixture may also oxidize if exposed
Aminopyrine …………………… 0.3 g - Should not be dispensed without correction, unless so to:
Codeine Sulfate ……………… 15.0 mg intended by the physician Air Excessive storage
Belladonna Extract ………… 10.0 mg Temperatures Light
Acetylsalicylic acid ………… 0.2 g IMMEDIATE INCOMPATIBILITY Overdilution Incorrect pH adjustment
M. Ft. caps. No. 1 DTD No. 12 Occurs instantaneously upon compounding Presence of catalysts.
Liquefies & becomes green within a few days Readily apparent due to:
Liquefaction due to a eutectic mixture formed by - Effervescence Undergo auto-oxidation (chain reaction type of
aminopyrine & ASA - Precipitation oxidation):
Green color is intensification of the green color of the - Color changes - Oils & fats, phenolic substances, aldehydes &
extract as it becomes wet. vitamins - used as antioxidants themselves
REMEDY: DELAYED INCOMPATIBILITIES REMEDY:
Changes avoided - by incorporating one grain of light MgO Other mixtures: Controlled by addition of still more reactive inhibitors to:
or MgCO3 in each capsule - React on such a slow rate that occurs have been termed. - Provide electrons &
Diluents - divided between the reacting ingredients, these - Occur without appreciable visible change/immediate - Receive the excess energy possessed by the activated
combined with gentle trituration & the remainder of the physical evidence of change molecules
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 B. REDUCTION
place & then absorb the liquid on sufficient kaolin or therapeutic activity is lost. Less common in Rxs although:
MgCO3 to give a suitable capsule fill - Silver, mercury, and gold salts may be reduced by light to
Rx is triturated until homogeneous then encapsuled & REMEDY: the metallic form
placed in tightly stoppered containers. Use of “Store in a Refrigerator” label
- Help decrease the rate of loss of activity C. RACEMIZATION
- Slows down hydrolysis, redox, or other chemical Conversion of an optically active form to an optically
reactions (occur more rapidly at rm temp) inactive form without changing chemical constitution
produces reduced pharmacological activity.
Use of“Shake well” label
- When applicable to promote uniform dosage
D. PRECIPITATION J. GELATINIZATION Hydrolysis Reactions (Molecular)
Two or more pharmaceuticals are combined Solutions form a gel when combined with certain Rx
- Formation of an insoluble substance which precipitates substances rarely encountered Sodium salicylate …………………………….. 4.0 g
from solution Example: Phenobarbital sodium ……………………… 0.6 g
Flocculent precipitates - Acacia solutions are gelatinized by ferric salt since acacia Vitamin B Complex Elixir …………………. 240.0 mL
- Develop several days after a stock solution or Rx is possesses carboxyl groups which may be cross-lined by M.
prepared trivalent ferric ions to form polymer chains Vit. B complex elixir has an acidic pH
- Due to delayed incompatibilities - Collodion is gelatinized by phenol (related bonding Alkalinity of the salts causes deterioration of the B
- Evidence of the growth of yeasts, molds or bacteria. reaction) vitamins via hydrolysis as well as eventual precipitation of
- Growth due indirectly to a chemical incompatibility if the acids of these sodium salts.
the preservative system is inactivated by a chemical K. DEVELOPMENT OF HEAT OR COLD Dispensing of the salts separately is suggested
reaction Chemical reactions with either liberation or absorption of
considerable amounts of heat Hydrolysis Reactions (Molecular)
E. EVOLUTION OF GAS Chem. reactions taking place spontaneously at rm. temp. Rx
Formed by chem. reaction between ingredients. do so with evolution of heat Penicillin G sodium ………………………………… 1,000,000 U
Example: - Compounds formed with evolution of heat tend to Syrup of Cherry, q.s. ad …………………………… 30 mL
Effervescence caused by the liberation of CO2 from the: - decompose when the temp. is raised M. Ft. Sol.
reaction of carbonates & acids in aqueous media, - Compounds requiring heat for their formation are more Hydrolysis of the penicillin salt occurs in the acidic medium
- Decomposition of syrups of paraaminosalicylic acid stable at higher temp. as well as precipitation of penicillin as the free acid
Neutral vehicle could be employed to slow down the rate
F. COLOR CHANGES L. HYDROLYTIC CHANGES of hydrolysis
Alterations in color Many substances hydrolyze in water & the change may be
Example hastened by heat, catalyst, esters, amides, certain metals M. INVISIBLE CHANGES
Laxative - phenolphthalein is colorless in acid solution but (Zn, Fe), etc. Chem. changes occur without visible evidence of the
purple in alkaline mixtures 1. Ionic hydrolysis reaction
- Ionized species + H+ or OH- of H2O → unionized insoluble Changes that destroy or change the therapeutic effect
G. EXPLOSIVE COMBINATION product
Oxidizing agents are chemically incompatible with - Special type of acid-base reaction (change of pH). N. DEVELOPMENT OF POISONOUS SUBSTANCES
reducing agents (redox reactions) - Manifested as precipitate of basic salts or hydrolysis Chem. reaction between two substances producing
Serious explosions may result from certain combinations - Ex. ZnCl2 + H2O → ZnOHCl + H+ products which are more toxic than the original
substances
H. CEMENTATION 2. Molecular hydrolysis Ex. KI + Hg2Cl2 (calomel) in the presence of moisture →
All or part of the ingredients of a Rx may set a mass of - Slower rate than ionic Hg+2 (toxic)
cement-like hardness. - Reduced therapeutic activity
Occurs when compounds from: O. IMPLOSION
- Hydrates (ex. Plaster of paris) polymerize, or Hydrolysis Reactions (Ionic) Weak bottles having thin spots or flaws may break
- Convert to new crystal forms 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
I. SEPARATION OF IMMISCIBLE LIQUIDS Sodium borate …………………….. 0.12 g removal of oxygen from the air in the bottle by oxidation
Immiscible liquids not soluble in the Rx Rose water, q.s. ad …………….. 30.00 mL of syrup
Ex. Chloral hydrate may separate as a layer of insoluble M.
chloral alcoholate in vehicles containing 10-50% alcohol & Formation of & subsequent hydrolysis of zinc borate P. OTHER TYPES OF CHEMICAL CHANGE
large amounts of certain soluble salts 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 I. ADVERSE DRUG INTERACTION b) Adverse effects
OCCUR: Noxious (lethal), unintended & occurs at doses normally - Predictable, dose dependent reactions unrelated to the
- When two drugs are administered together to produce a used in man for prophylaxis or diagnosis or therapy of goal of therapy
response which differs in nature or intensity from that disease. - Often produced by the same drug-receptor interaction
which was intended Occurs when the action of a prescribed drug is: responsible for the therapeutic effect, differing only in
- At the site of the drug action - Potentiated, inhibited or otherwise modified in the tissue/s or organ/s affected.
the patient by an interactant so that an unfavorable Ex. Atropine –dryness of the mouth
CONSEQUENCES: response to the drug is elicited codeine – constipation
- Therapeutic effectiveness reduced or delayed (physical or Some have been:
chem. reaction) - associated with inheritable disorders some of which are 2. Type B (Bizarre)
- Loss of activity (hydrolysis/oxidation) related to race - Totally abnormal effects, unrelated from the drug’s
- Delay in the release or absorption of drug (Complexation known pharmacological actions
or combination of drugs with proteins, tannins, TYPES OF ADVERSE DRUG REACTIONS: - Very small doses of the drug may elicit the reaction once
surfactants & other large molecules) A. Side effects allergy or idiosyncrasy is established.
Troublesome, secondary pharmacological effects & usually Ex. Penicillin hypersensitivity –anaphylaxis; reaction
RESPONSIBLE: not very dangerous disappears on discontinuation of the drug.
- Physician rather than the pharmacist but the pharmacist Useful in determining when the:
may inform the physician to eliminate: - Effective dose is reached 3. Type C (Continuous)
- Errors in Rx writing/interpretation - May even be beneficial as with the sedative effects of - Long term effects usually related to the dose and
- Overdose (excessive single dose/too frequent antihistamine syrups given to children duration of treatment.
administration) Minimized & desired activity retained by: Ex. Ethambutol – optic neuropathy
- Contraindicated drugs (steroids/peptic ulcer) - Reducing the dosage or using the proper combination of
- Synergistic/Antagonistic effects drugs 4. Type D (Delayed)
- Alteration of Rx order requires permission of prescriber - Carcinogenesis (hormonal/gene toxicity)
B. Extension Effects - Adverse effects associated with reproduction
DRUG INTERACTIONS Excessive pharmacologic actions normally dose-related (teratogens)
Frequently applied to those situations: Show up in patient given enough drug may develop rapidly
- Effects of one drug are altered by the prior or concurrent or may produce a delayed toxic effect through 5. Type E (Ending of use/Withdrawal syndromes)
administration of another cumulative/increasing build up. - Alcohol-delirium tremens (disorientation and visual
- Dietary item influences the activity of a drug (e.g., cheese Ex. Cumulative toxic effects which are undesirable hallucinations)
& monoamine oxidase inhibitors) Yellowing of teeth in the young child given tetracycline - barbiturates – restlessness, mental confusion,
- A drug causes alterations of laboratory test values Ataxia after chlorpromazine convulsions
- A drug essentially interacts with itself (e.g. by stimulating Hypersensitivity reactions also represent overdose of the
its own metabolism) exquisitely sensitive individual given a normal size dose or 6. Type F (Failure of efficacy)
due to: - Therapeutic failure can sometimes be attributed to a lack
Mechanisms of drug interaction: - allergies or other immune reactions (require prior of efficacy of drug products.
1. DI at the site of absorption – tetracycline (antacids/dairy sensitization) - Examples:
products); enteric coated (antacid) - Failure to control infection/ apparent antimicrobial
2. DI at the site of distribution – warfarin CLASSIFICATIONS OF ADR resistance; uncontrolled hypertension
3. DI at the site of excretion –probenecid/penicillin 1. Type A (Augmented) – actions related to the - Failure of efficacy of the drug can be the result of
4. Drug biotransformation pharmacological activity of the drug imperfect or counterfeit manufacture of the product.
a) Extension effects
DRUG INTERACTIONS - Predictable, dose related responses arising from an CAUSES OF ADR
May either be: extension of therapeutic effect 1. Pharmaceutical causes – altering the quantity of drug
- Adverse drug interaction - Prevention is adjustment of dosage regimen. available for systemic absorption; influencing release rates
- Beneficial Drug Interaction Ex. Benzodiazepines (anxiety neurosis) – sedation Systemic availability of drug influenced by:
and falls/trauma. particle size, nature and quantity of excipients and coating
materials
2. Pharmacokinetic causes – the way a drug is handled by CLINICAL FACTORS IN DI Ex. of acceptable corrections:
the body during ADME may affect humans in as adverse - Diagnostic errors Use of: modified mixing order
manner; ototoxicity with aminoglycosides when used in - Prescribing errors - Dispensing with a “shake well” label
patients with renal failure. - Insufficient study of the patient - Suspension or emulsification with official agents
- Contraindicated drugs - Most appropriate form of the drug for the vehicle
3. Pharmacodynamic causes – increased sensitivity of - Excessive single dose prescribed,
target organs in the body to drugs - Excessive daily dose - Other procedures where no therapeutically important
- Additive and synergistic combination change is made in the dosage or ingredients of the
PREDISPOSING/INFLUENCING FACTORS IN ADR - Antagonistic combination formula.
Patient-related factors - Rx writing errors
- Presence of renal, hepatic, and cardiac disease - Nomenclature error Borderline cases (depending on the Rx or
- Age - Dosage form error Relationship between the pharmacist & physician:
- Previous ADR or drug allergy - Drug Administration and Patient Care - Addition of inert ingredients such as:
- Sex -- placebo and psychosomatic factors diluents, stabilizers, buffers, stiffening agents,
- Genetic influence --unpalatability preservatives & other procedures in which the dose or
- Miscellaneous ( diet, smoking, alcohol, environmental activity is not altered appreciably
exposures) IV. COMBINATION OF FACTORS
More than one error or drug interaction problem may Procedure requiring approval of the physician:
Drug-related factors occur in a clinical situation. Addition of materials requiring a charge in the dose
- Pharmaceutical properties Cause never determined although: Addition of:
- Pharmacokinetic properties - It is the joint responsibility of the physician & pharmacist - Unofficial suspending agents, emulsifiers, chelating
- Pharmacodynamic effects to find the cause & eliminate any further similar agents or other materials which may adversely affect the
situations. stability
II. BENEFICIAL DRUG INTERACTION - Omission of troublesome ingredients having little
Desired & intended, when a combination of medications PHARMACIST: therapeutic activity
produces: Use his training to investigate the pharmaceutical aspects: - Filtering out inactive sediments
- Improved therapy - Possible drug instability, physical, chemical, therapeutic - Dispensing a troublesome ingredient separately
- Perhaps a greater margin of safety incompatibilities while cooperating with the physician in - Changing a brand from that specified
- More appropriate onset or duration of action exploring clinical aspects (possible drug interactions, - Changing the dosage forms, i.e., substituting capsules for
- Lowered toxicity adverse drug reactions, diagnostic, prescribing or powders, pills, tablet, triturates, etc. and other important
- Enhanced potency with diminished side effects of drug administration errors, etc.) changes.
may be modified by prior or concurrent administration of - Pertinent physical, chemical, pharmacodynamics,
another drug pharmacological & pharmaceutical factors USE PHARMACEUTICAL KNOWLEDGE
- Improved therapy is possible by judicious use of In correcting the problems, the following procedures
combined medication but CORRECTION OF INCOMPATIBILITIES should be considered first:
- Serious adverse effects may result from drug interaction - Consult the physician - Modify the mixing order
- Use pharmaceutical knowledge - Dispense with a “shake well” label
MULTIPLE DRUG THERAPY IS JUSTIFIED IF IT PROVIDES: - Add an ingredient - Dispense with a “store in a refrigerator” label
- Greater efficacy than can be achieved with full doses of - Remove an ingredient - Complete the reaction before packing
single drugs - Change the vehicle - Protect from air, light & moisture
- Greater margin of safety - Change an ingredient - Add an Ingredient
- More satisfactory onset or duration of effect - Change the dosage form - Suspending agents
- Read the literature - Emulsifying agents
REASONS FOR INCREASED EVIDENCE OF DRUG INTERACTIONS: - Consult the Physician - Inert solubilizing or miscibility-increasing ingredients
- Drug potency - Diluents
- Patients see several physicians - Method used on the Rx - Stiffening or softening agents
- Concurrent use of Rx & non-Rx drugs -- discuss the matter with prescriber & co-workers - Remove an Ingredient
- Patient’s non-compliance - Discard the inactive sediment
- Drug abuse - Separate the two prescriptions
- Change the Vehicle Rx - Addition of the tincture with rapid stirring yields a fine
- Increase the volume of mixture & increase dose Ephedrine sulfate ………………………………………..0.25 g colloidal dispersion
- Decrease volume of mixture & decrease dose Menthol ……………………………………………………… 0.02 g - No suspending agent is necessary
- Change solvent & use the same dose Mineral oil, light, q.s. ……………………………… 30.0 mL
- Change an Ingredient M. Ft. Sol. PHYSICAL COMPLEXATION
-- Use the most soluble form - Alkaloidal salt is not oil-soluble Rx
-- Use the most stable form - Substitution of an anhydrous ephedrine base will permit Phenol ……………………………………….…. 1.0 g
- Change the Dosage Form preparation of a clear solution Polyethylene glycol – 400 ……………… 10.0 mL
--Use a more suitable dosage form ZnO ……………………………………………….. 15.0 g
--Use a different brand Rx Purified water, q.s. ad ……………………. 100.0 mL
- Read the literature Peru Balsam ………………………………….2.0 g M. Ft. Lotion.
Petrolatum, q.s. ………………………… 30.0 mL - Complexation of the phenol with the ether oxygens of
PREVENTING AND MINIMIZING INCOMPATIBILITIES M. Ft. Oint. the PEG – 400 will produce an unsatisfactory suspension,
- Each drug should be mixed thoroughly after it is added to - Granular ointment results because the semipolar as well as inactivate the phenol
the preparation (phenolic) components of the balsam are not miscible - Substitution of bentonite magma for PEG will permit
- Solutions should be administered promptly after they are with the completely non-polar base preparation of a satisfactory product
mixed to minimize the time available for a potential - Compounds possessing the proper balance of polar &
reaction to occur non-polar groups, so that they can associate with both OXIDATION – REDUCTION
- The number of drugs mixed together in an IV solution the petrolatum & the balsam, will permit the preparation Rx
should be kept to a minimum of a smooth product. Castor oil will serve this function. Sodium Salicylate ………………………………….. 8.0 g
- If a Rx calls for unfamiliar drugs or IV fluids, compatibility - If balsam is first mixed with about an equal amount of Sodium Bicarbonate ……………………………… 16.0 g
references should be consulted castor oil and this mixture incorporated into the Peppermint water, q.s. ad …………………….. 180.0 mL
- Drugs.com – to check for drug incompatibilities petrolatum, a smooth ointment results. M. Ft. Sol.
- Solution darkens on standing
EXAMPLES OF INCOMPATIBILITIES Rx - Change attributed to the alkaline catalyzed oxidation of
INSOLUBILITY Magnesium carbonate ……………………………….7.5 g the salicylate to a quinoid form number of substances are
Rx Sodium bicarbonate …………………………………. 15.0 g useful as antioxidants in retarding the color development
Potassium iodide ……………….30.0 g Citric acid …………………………………………………. 15.0 g and, in this formula, 0.1% sodium bisulfite serves this
Phenobarbital ……………………… 1.0 g Purified water, q.s. ad ……………………………… 500.0 mL purpose.
Thiamine HCl Elixir, q.s. ad…… 240.0 mL M. Ft. Sol
M. Ft. Sol. - Final appearance of this Rx depends on the order of ACID – BASE REACTIONS
- Alcoholic conc. of the elixir is not sufficient to dissolve mixing Rx
the Phenobarbital or to maintain it in solution - If NaHCO3 is added to a solution of the citric acid, and Cocaine HCl ………………………….. 0.3 g
- A suspension might be prepared but because of the the MgCO3 is added last, the solution will be incomplete. Boric acid …..
potency of the Phenobarbital & the danger involved if the - If MgCO3 is added to the solution of citric acid first, aa …………………………………………. 1.2 g
patient did not uniformly disperse this drug before taking soluble Mg citrate will be formed Sodium borate
a dose, dissolution is preferable - NaHCO3 will be soluble in this mixture and a clear Purified water, q.s. ad …………. 60.0 mL
- Conc of alcohol required to maintain this amount of solution will be obtained. - Alkalinity imparted to the solution by the sodium borate
Phenobarbital in solution is about 27%. causes precipitation of the water-insoluble cocaine base.
- Knowledge of alcoholic conc of the elixir would permit Rx Elimination of the sodium borate prevents this
calculation of the amount of alcohol that must be added Tr. Benzoin Compound …………………………. 5.0 mL incompatibility.
the Phenobarbital is dissolved in this alcohol; the Glycerin ………………………………………………… 15.0 mL - This reaction is typical of most amine salts in the
thiamine lost be replaced of the elixir and the potassium Rose water, q.s. ad ……………………………….. 100.0 mL presence of bases or basic salts
iodide dissolved in the elixir, and the two solutions are M. Ft. Lotion.
mixed. - Resins & ether components of the tincture are soluble
- Sodium Phenobarbital could not be substituted in this only in high alcoholic vehicles
system because the acidity of the elixir will precipitate - Change in solvent system results in an unavoidable
free Phenobarbital and the alkalinity of the sodium precipitate
Phenobarbital may cause some hydrolysis of the thiamine
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