INCOMPATIBILITIESINCOMPATIBILITIES

IncompatibilitiesIncompatibilities

IncompatiblesIncompatibles are substances which have are substances which have opposite medicinal properties, or opposite medicinal properties, or substances when mixed together, react substances when mixed together, react chemically to produce other substances. chemically to produce other substances. An understanding of incompatibilities can An understanding of incompatibilities can save the pharmacist valuable time in save the pharmacist valuable time in compounding as well as ensure the compounding as well as ensure the therapeutic efficiency of the products.therapeutic efficiency of the products.Incompatibilities range from minor to Incompatibilities range from minor to dangerous.dangerous.

IncompatibilitiesIncompatibilities

Incompatibilities are divided into three Incompatibilities are divided into three classes:classes: Therapeutic incompatibilities Therapeutic incompatibilities Physical incompatibilities Physical incompatibilities ChemicalChemical incompatibilities incompatibilities

Types of IncompatibilitiesTypes of Incompatibilities

1. Therapeutic Incompatibility1. Therapeutic IncompatibilityThey exist when the response to one They exist when the response to one or more drug is of different nature or or more drug is of different nature or intensity than that intended by the intensity than that intended by the prescriber.prescriber.

When circumstances produce a feeling When circumstances produce a feeling of doubt on the part of the pharmacist, of doubt on the part of the pharmacist, the prescribing physician should be the prescribing physician should be consultedconsulted. .

Therapeutic incompatibilityTherapeutic incompatibility

1. Synergistic (or additive) combination1. Synergistic (or additive) combinationWhen certain drugs having the same When certain drugs having the same pharmacologic action are prescribed together, pharmacologic action are prescribed together, the combined action they produce is greater than the combined action they produce is greater than the sum of their individual actions.the sum of their individual actions.

Such combinations should be in reduced amount.Such combinations should be in reduced amount.

The synergistic action will sometimes be desired The synergistic action will sometimes be desired to decrease toxicity or reduce cost of prescriptionto decrease toxicity or reduce cost of prescription

Therapeutic incompatibilityTherapeutic incompatibility

Synergistic (cont.); examples of useful Synergistic (cont.); examples of useful synergistic effectsynergistic effectCombinations of sulfonamides show less Combinations of sulfonamides show less nephrotoxicity than a single sulfonamide.nephrotoxicity than a single sulfonamide.

Neomycin – erythromycin combination has a Neomycin – erythromycin combination has a broader spectrum than either antibiotic alone.broader spectrum than either antibiotic alone.

Aspirin – codeine combination reduces the Aspirin – codeine combination reduces the amount of expensive codeine required.amount of expensive codeine required.

Therapeutic incompatibilityTherapeutic incompatibility

2. Antagonistic combinations2. Antagonistic combinationsWhen two or more drugs having opposite When two or more drugs having opposite pharmacological action are prescribed together, pharmacological action are prescribed together, their actions cancel each other and the resulting their actions cancel each other and the resulting prescription will have no therapeutic action.prescription will have no therapeutic action. Stimulants with sedatives (hypnotics) e.g. caffeine Stimulants with sedatives (hypnotics) e.g. caffeine

with chloral hydrate.with chloral hydrate. Purgatives with antidiarrheals e.g. MgSoPurgatives with antidiarrheals e.g. MgSo44 with tannins with tannins

Acidifiers with alkalinizers e.g. aspirin with AL(OH)Acidifiers with alkalinizers e.g. aspirin with AL(OH)33..

Therapeutic incompatibilityTherapeutic incompatibility

3. contraindication3. contraindicationAre drugs when prescribed together Are drugs when prescribed together may lead to increased toxicity or may lead to increased toxicity or decrease activity.decrease activity.

Tetracycline is contraindicated with Tetracycline is contraindicated with any drug containing Caany drug containing Ca2+2+ ions as it ions as it form nonform non--absorbable complex.absorbable complex.

Inactivation of sulfa drugs by Inactivation of sulfa drugs by procaine HCI.procaine HCI.

Therapeutic IncompatibilityTherapeutic Incompatibility

44. Dosage Error:. Dosage Error:

can result from the administration of a single can result from the administration of a single high dose, or the too frequent administration.high dose, or the too frequent administration.

R/ R/

Atropine sulphateAtropine sulphate 6 mg6 mg

PhenobarbitalPhenobarbital 360 mg 360 mg

Ft. caps, i mitte xiiFt. caps, i mitte xii

sig. caps, i t.d.ssig. caps, i t.d.s

- Dosing errors, unclear prescription- Dosing errors, unclear prescription

Therapeutic IncompatibilityTherapeutic Incompatibility

Dosage errorsDosage errors

Rx Rx

Codeine phosphateCodeine phosphate 15 mg15 mg

Ammonium chlorideAmmonium chloride 500 mg500 mg

Ft. caps, i mitte xxFt. caps, i mitte xx

sig; caps, ii q.h.sig; caps, ii q.h.

2. Physical Incompatibilities2. Physical Incompatibilities

Physical  incompatibilities  are  often  called  phar-Physical  incompatibilities  are  often  called  phar-maceutical  incompatibilities  and  are  evidenced maceutical  incompatibilities  and  are  evidenced  by  the failure of the drugs to combine properly.  by  the failure of the drugs to combine properly.

These incompatibilities produce a mixture which is These incompatibilities produce a mixture which is unacceptable in appearance and taste and may unacceptable in appearance and taste and may result in non-uniform dosage form.result in non-uniform dosage form.

1.Incomplete solution:1.Incomplete solution: Gums are insoluble in alcohol.Gums are insoluble in alcohol. resins are insoluble in waterresins are insoluble in water

Physical IncompatibilitiesPhysical Incompatibilities

2. Precipitation:2. Precipitation: Resins are precipitated from alcoholic solution Resins are precipitated from alcoholic solution

when water is addedwhen water is added Camphor and volatile oils are salted out from Camphor and volatile oils are salted out from

their aromatic water when soluble salts are their aromatic water when soluble salts are addedadded

3. 3. Separation of immiscible liquids.Separation of immiscible liquids.

4. Eutexia; formation of eutictic mixture.4. Eutexia; formation of eutictic mixture.5. Incorrect form prescribed,e.g. alkaloidal salt 5. Incorrect form prescribed,e.g. alkaloidal salt

dissolve in liquid paraffin.dissolve in liquid paraffin.6. Adsorption at solid surface; Adsorption on solid 6. Adsorption at solid surface; Adsorption on solid

surfaces; such as adsorption of anti-microbial surfaces; such as adsorption of anti-microbial agents on rubber closure or plastic container.agents on rubber closure or plastic container.

3. Chemical Incompatibilities3. Chemical Incompatibilities

This type of incompatibility exists when This type of incompatibility exists when agents are prescribed that react chemically agents are prescribed that react chemically when mixed, altering the composition of one when mixed, altering the composition of one or more of the constituents. or more of the constituents. 

Examples;Examples;

- formation of precipitate- formation of precipitate

- evolution of gas- evolution of gas

- colour change - colour change

Evolution of gas:Evolution of gas:R/R/ amm. Carbonateamm. Carbonate

Amm. ChlorideAmm. Chloride

Acetic acidAcetic acid

syrup of cherrysyrup of cherry

Fait solutionFait solution

Amm. Carb. + acetic acid Amm. Carb. + acetic acid CO2CO2

Manifestations of IncompatibilityManifestations of Incompatibility

Insolubility of prescribed agent in vehicle Insolubility of prescribed agent in vehicle (physical) (physical) Immiscibility of two or more liquids (physical) Immiscibility of two or more liquids (physical) Precipitation due to change in menstrum that Precipitation due to change in menstrum that results in decreased solubility (physical) results in decreased solubility (physical) Eutexia-the liquefaction of solids mixed in Eutexia-the liquefaction of solids mixed in dry state (physical)dry state (physical)Cementation of insoluble ingredients in liquid Cementation of insoluble ingredients in liquid mixtures (physical) mixtures (physical)

Manifestations of IncompatibilityManifestations of Incompatibility

Change in color (chemical)Change in color (chemical)Oxidation-reduction or explosive reaction Oxidation-reduction or explosive reaction (chemical) (chemical) Precipitation due to chemical reaction Precipitation due to chemical reaction (chemical) (chemical) Inactivation of sulfa drugs by procaine HCI Inactivation of sulfa drugs by procaine HCI (therapeutic)(therapeutic)Inactivation of tetracycline by calcium ions Inactivation of tetracycline by calcium ions (therapeutic) (therapeutic)

Corrective MeasuresCorrective Measures

Corrective MeasuresCorrective Measures Addition of an ingredient that does not alter the Addition of an ingredient that does not alter the therapeutic value.therapeutic value.Change of an ingredient. Minor changes such as a Change of an ingredient. Minor changes such as a soluble form of an ingredient for an insoluble form soluble form of an ingredient for an insoluble form are included. are included. Change of a solvent. Change of a solvent. The utilization of special techniques in The utilization of special techniques in compounding, such as treating each ingredient compounding, such as treating each ingredient separately.separately.Omission of an agent that has no therapeutic value, Omission of an agent that has no therapeutic value, or that may be dispensed separately.or that may be dispensed separately.Utilization   of   special   techniques   in   com- Utilization   of   special   techniques   in   com- pounding pounding

Intentional incompatibilitiesIntentional incompatibilities

Intentional Therapeutic incompatibilitiesIntentional Therapeutic incompatibilities

Such circumstances rarely occur, but when they do it Such circumstances rarely occur, but when they do it does not necessarily indicate a moment of forgetfulness does not necessarily indicate a moment of forgetfulness on the part of the physician. Such agents may have been on the part of the physician. Such agents may have been used together in order for one agent to modify the used together in order for one agent to modify the activity of the other. activity of the other. Examples:Examples:

Atropine should antagonize the depressant effect of Atropine should antagonize the depressant effect of morphine to the respiratory tract.morphine to the respiratory tract.

Central nervous system stimulants may be used to Central nervous system stimulants may be used to overcome the drowsiness produced by anti-histaminic. overcome the drowsiness produced by anti-histaminic.

A mild laxative antacid such as Mg(OH)A mild laxative antacid such as Mg(OH)22 may be used to may be used to overcome the constipating effect of an astringent antacid overcome the constipating effect of an astringent antacid such as AL(OH)such as AL(OH)33..

Intentional Chemical IncompatibilityIntentional Chemical Incompatibility

Strong iodine solution U.S.P. (Lugol’s solution)Strong iodine solution U.S.P. (Lugol’s solution)

R/R/

IodineIodine 50 gm 50 gm

Potassium iodide 100 gmPotassium iodide 100 gm

purified water ad 1000 mlpurified water ad 1000 ml

Iodine dissolves in potassium iodide to form Iodine dissolves in potassium iodide to form the water soluble Ithe water soluble I33 complex. complex.

Intentional chemical incompatiblesIntentional chemical incompatiblesCarbonaeous mixtureCarbonaeous mixture(Postion Revier Mixture):(Postion Revier Mixture):Solution A: R/Solution A: R/ Sodium bicarbonateSodium bicarbonate 3.5 gm3.5 gm

Simple syrupSimple syrup 30.0 ml30.0 mlWater toWater to 150 ml150 ml

Solution B: R/Solution B: R/ Citric acidCitric acid 4.0 gm4.0 gmSyrup lemonSyrup lemon 30.0 ml30.0 mlWater toWater to 150 ml150 ml

Fait Mist. A and B, Mitte 50 ml of eachFait Mist. A and B, Mitte 50 ml of each

Sig.:Sig.: one tablespoonful from solution A is mixed with one tablespoonful from solution A is mixed with an an equal volume of solution B and the mixture is equal volume of solution B and the mixture is taken when effervescence is about to cease taken when effervescence is about to cease

Intentional Physical incompatibilitiesIntentional Physical incompatibilities

Tincture myrh is diluted with water to give Tincture myrh is diluted with water to give a precipitate which is used as a gargle in a precipitate which is used as a gargle in the treatment of tonsillitis.the treatment of tonsillitis.