INCOMPATIBILITY

Q.1: Define therapeutic incompatibility. What are the various types and causes of
therapeutic incompatibility?
Therapeutic Incompatibility:-When the intensity or nature of action drug is different from that
intended by prescriber, then such effects are termed as therapeutic incompatibility.
Various types and causes of therapeutic incompatibility-
1. Error in dosage:-
 It is error in writing or interpreting the prescription order.
 The most serious type of dosage error in the dispensing is overdose of a medication.
 So it is the duty of a pharmacist to check the prescription before dispensing it.
Rx
Atropine sulphate -------0.006gm
Phenobarbitone-----------0.015gm
Asprin ---------------------0.300gm
Prepare 10 capsules
In this prescription, the quantity of atropine sulphate in each capsule is more than its minimum
recommended dose of 2mg. So the prescription is referred back to the prescriber to correct the
overdose of atropine sulphate.
2. Wrong drug or dosage form:-
 There are certain drugs which have quite similar name & there is always a danger of
dispensing of wrong drug.
 For e.g. Prednisone & Prednisolone, Digoxin & Digitoxin
 Sometimes many drugs are available in different dosage forms & hence dosage form should
be clearly mentioned on prescription.
3. Contra-indicated drugs:
 There are certain drugs which may be contra-indicated in a particular disease or particular
patient who is allergic to it. For e.g. Corticosteroids are contraindicated in patients having an
active peptic ulcer.
 Penicillin & sulpha drugs are contra-indicated to the patients who are allergic to it.
4. Synergistic & antagonistic drugs:-
Many drugs exhibit synergism & antagonism when administered in combination.
 Synergism:- When two drugs are prescribed together, they increase the activity of each other.
For e.g. a combination of aspirin & paracetamol increases the analgesic activity.
 Antagonism:-When two drugs having the opposing pharmacological effects are prescribed
together antagonism occurs. For e.g. Acetyl acetic acid & probenecid are used in the treatment of
gout, the combination of these lead to neutralization.
5. Drug interaction:-
 The effect of one drug is altered by prior or simultaneous administration of another drug or
any food items & it is corrected by proper adjustment of dosage, or appropriate directions.
For e.g.
Rx
Tetracycline HCL----------- 250mg
Send 10 capsules.
Direction: Take 1 capsule every 6 hours with milk.
In this tetracycline is inactivated by calcium which is present in milk. So tetracycline capsule
should not be taken with milk. So prescription may by refer back to the physician.
 INCOMPATIBILITY

Q.2.: Report the incompatibility in the following prescription with method to correct it.
Rx
Codeine phosphate -0.5 gm
Prepare 10 powders
Label-one to be taken at bed time.
Solution:
Its Therapeutic incompatibility of error in dose.
Therapeutic dose of Codeine phosphate is 5mg, prescriber has written 0.5gm which is 500 mg.
method of correction:
Refer back prescription to prescriber for correction of dose

Q.3.: List reasons causing therapeutic incompatibility.

Following are reasons causing therapeutic incompatibility
 Error in dosage.
 Wrong dose or dosage form.
 Synergism and Antagonism drug.
 Contraindication.
 Drug interaction

Q.4.: Define incompatibility. What is tolerated and adjusted incompatibility?

Incompatibility:- Incompatibility occurs as a result of mixing two or more antagonistic
substances & an undesirable product is formed which may affect the safety, efficacy &
appearance of the pharmaceutical preparation.
1. Tolerated incompatibility -
In this type of incompatibility, chemical reaction can be reduced by mixing the solutions in dilute
forms or by changing the order of mixing but no alteration is made.
Example (any one example)
Rx
Sodium bicarbonate ………… 1g
Borax ……………………….. 1 g
Phenol ………………………. 0.5g
Glycerine …………………….. 20 ml
Water …………….upto…….. 90 ml
Make a spray solution,
When sodium bicarbonate, borax and glycerine are mixed together in the presence of water, a
reaction takes place with the evolution of carbon dioxide. If the mixture is dispensed as such,
there are chances of bursting the bottle. Therefore, mix these ingredients in an open vessel until
the evolution of carbon dioxide ceases add phenol and transfer the mixture to a bottle.
 INCOMPATIBILITY

2. Adjusted incompatibility -

In this type of incompatibility, change in the formulation is needed with a compound of equal
therapeutic value
e.g. in the mixture of caffeine citrate and sodium salicylate, caffeine citrate is replaced with
caffeine.
Example (any one example)
Rx Caffeine citrate …………… 1g
Sodium salicylate …………. 3g
Water …………………. 90ml
Caffeine citrate is a mixture of equal weights of caffeine and citric acid. the citric acid present in
caffeine citrate reacts with sodium salicylate to liberate salicylic acid which get precipitated. If
caffeine is used instead of caffeine citrate it forms a soluble complex with sodium salicylates.
Hence substitute caffeine citrate with half as much caffeine as that of caffeine citrate to form a
clear mixture.

Q.5.:Report the incompatibility in following prescription how will you correct it ?

Rx
Quinine sulphate ………1.5 gm
Dilute sulphuric acid …..4ml
Potassium iodide ……….8gm
Water 9.5 ……………200 ml
Fiat Mistura
Signa- Cochleare amplum quartis horis summendum
Identification of incompatibility:
Dil. sulphuric acid is added to dissolve the quinine sulphate, but potassium iodide present in
formulation react with dil. sulphuric acid to form hydroiodic acid further it gets oxide to form
free iodine, free iodine, hydroiodic acid and quinine sulphate together form iodosulphide of
quinine called “herapathite”
It form olive green scales after three days stay.
Correction
1. Dispense it for three days.
2. Dispense in two different bottles one bottle containing dil. sulphuric acid with quinine
sulphate and in another bottle potassium iodide and water. Instruct the patient to mix them before
the dose actually taken.
 INCOMPATIBILITY
Q.6.: What are the various approaches to overcome incompatibility due to liquification
Liquification: When certain low melting point solids are mixed together they form a new
chemical compound which has melting point lower than room temperature, therefore they
become liquid at room temperature.
Example:
Rx
Menthol --------------------------- 5g.
Camphor -------------------------- 5g.
Ammonium chloride ------------ 30g.
Light magnesium carbonate ---- 60g.
Send five powders
The combination forms eutectic mixture.
The substance can be dispensed by any one of the following methods;
i) Triturate together to form liquid and mixed with an absorbent like light kaolin or light
magnesium carbonate to produce free flowing powder.
ii) The individual medicaments are powdered separately and mixed with absorbent and then
combined together lightly and filled in suitable container
Q.7.: Define tolerated and adjusted incompatibility.
Tolerated
In this type of incompatibility, chemical reaction can be reduced by mixing the solutions in dilute
forms or by changing the order of mixing but no alteration is made.
Adjusted
In this type of incompatibility, change in the formulation is needed with a compound of equal
therapeutic value e.g. in the mixture of caffeine citrate and sodium salicylate, Caffeine citrate can
be replaced with caffeine.

Q.8.:Define 'Incompatibility'. Explain any one of physical incompatibility with method to

overcome it.
Definition:
Incompatibility occurs as a result of two or more antagonistic substances & an undesirable
product is formed which may affect the safety, efficacy & appearance of the pharmaceutical
preparation.
Types of Physical Incompatibility:
1. Immiscibility.
2. Insolubility.
3. Precipitation.
4. Liquefaction.
 INCOMPATIBILITY
1. Immiscibility:
Castor oil is immiscible in water therefore emulsifying agent is added to form emulsion.
Rx
Castor oil ....... 15 ml
Water ............. 6.0 ml
In this prescription castor oil is immiscible with water. To overcome this incompatibility an
emulsifying agent is used to make a good emulsion. Make an emulsion
2. Insolubility:
Phenacetin is indiffusible solid which is insoluble in water therefore suspending agent is added to
form suspension of phenacetin.
Rx
Phenacetin........ 3 g
Caffeine ............. 1 g
Orange syrup ... 12 ml
Water ................ 90 ml
In this prescription phenacetin is an indiffusible substance. Compound powder of tragacanth or
mucilage of tragacanth is used as a suspending agent to make a stable suspension
3. Precipitation:
Tincture containing resins when added into the water forms precipitate, therefore to disperse it
uniformly a suspending agent is added. When the precipitate is diffusible then no need of adding
suspending agent
Rx
Tincture of benzoin ......... 5.0 ml
Glycerin .............................. 15 ml
Rose water ........................ 100 ml
Tincture benzoin compound contains resins. The change in solvent system results in an
unavoidable precipitate. Addition of tincture with rapid stirring yields a fine colloidal dispersion.
So there is no need of any suspending agent
4. Liquefaction:
Eutectic mixture: when two or more substance are mixed together they are going to form new
chemical compound which has melting point lower than the room temperature, therefore they are
liquid at room temperature.
To correct this incompatibility a inert solid substance is added to form free flowing powder.
Rx
Menthol ..................................... 5 g
Camphor................................... 5 g
Ammonium Chloride........... 30 g
Light Mg carbonate ............... 60 g
Prepare a powder
In this prescription menthol, camphor and ammonium chloride get liquefied on mixing with each
other. To dispense this prescription, menthol, camphor and ammonium chloride are triturated
together to form liquid. Add light magnesium carbonate and mix it thoroughly to make free
flowing powder.
 INCOMPATIBILITY
Q.9.: Report the incompatibility if any in the following preparation and suggest suitable
Method of correction.
Rx
Quinine sulphate ………1.5 gm
Dilute sulphuric acid …..4ml
Potassium iodide ……….8gm
Water upto ……………200 ml
Prepare mixture, send ………100 ml
Dil. sulphuric acid is added to dissolve the quinine sulphate, but potassium iodide present in
formulation react with dil. sulphuric acid to form hydroiodic acid further it gets oxide to form
free iodine, now free iodine, hydroiodic acid and quinine sulphate together form iodosulphide of
quinine called “herapathite”
It form olive green scales after three days stay.
Correction:
1. Dispense it for three days.
2. Dispense in two different bottles one bottle containing dil. sulphuric acid with quinine
sulphate and in another bottle potassium iodide and water. Instruct the patient to mix them before
the dose actually taken.
Describe adjusted incompatibility with example.
Adjusted incompatibility - In adjusted incompatibility the chemical interaction can be
prevented by addition or substitution of one of the reactant .
e.g. caffine citrate substituted with caffine in sodium salicylate & caffine mixture. or any other
example of adjusted incompatibility

Q.10. Explain any three Therapeutic incompatibilities.

Therapeutic incompatibility:-
1. Error in dosage:-
 It is error in writing or interpreting the prescription order.
 The most serious type of dosage error in the dispensing is overdose of a medication.
 So it is the duty of a pharmacist to check the prescription before dispensing it.
E.g.
Rx
Atropine sulphate -------0.006gm
Phenobarbitone-----------0.015gm
Aspirin ---------------------0.300gm
Prepare 10 capsules
In this prescription, the quantity. of atropine sulphate in each capsule is more than its minimum
recommended dose. So the prescription is referred back to the prescriber to correct the overdose
of atropine sulphate.
2. Wrong drug or dosage form:-
 There are certain drugs which have quite similar name & there is always a danger of
dispensing of wrong drug.
 For e.g. Prednisone & Prednisolone, Digoxin & Digitoxin
 Sometimes many drugs are available in different dosage forms & hence dosage form
should be clearly mentioned on prescription.
 INCOMPATIBILITY
3. Contra-indicated drugs:-
 There are certain drugs which may be contra-indicated in a particular disease or particular
patient who is allergic to it. For e.g. Corticosteroids are contraindicated in patients having
an active peptic ulcer.
 Penicillin & sulpha drugs are contra-indicated to the patients who are allergic to it.
4. Synergistic & antagonistic drugs:-
Many drugs exhibit synergism & antagonism when administered in combination.
 Synergism:- When two drugs are prescribed together, they increase the activity of each other.
For e.g. a combination of aspirin & paracetamol increases the analgesic activity.
 Antagonism:-When two drugs having the opposing pharmacological effects are prescribed
together antagonism occurs. For e.g. Acetyl acetic acid & probenecid are used in the treatment of
gout, the combination of these lead to neutralization.
5. Drug interaction:-
 The effect of one drug is altered by prior or simultaneous administration of another drug or
any food items & it is corrected by proper adjustment of dosage, or appropriate directions.
For e.g.
Rx
Tetracycline HCL----------- 250mg
Send 10 capsules.
Direction: Take 1 capsule every 6 hours with milk.
In this tetracycline is inactivated by calcium which is present in milk. So tetracycline capsule
should not be taken with milk. So prescription may by refer back to the physician.

Q.11. Explain the term Tolerated Incompatibility

In tolerated incompatibilities, the chemical interaction can be minimized by changing the order
of mixing or mixing the solution in dilute forms but no alteration is made in the formulation.
Example- If precipitate is diffusible type ,since therapeutic value is not changed, it is tolerated as
it is, and no alteration is made.
Q.12. Explain herapath reaction for quinine.
Oxidation of iodides with quinine sulphate : Quinine sulphate is not freely soluble in water.it is
made soluble in presence of sulphuric acid. The sulphuric acid librates hydroiodic acid from the
potassium iodide and the hydroiodic acid is partly oxidized by the sulphuric acid, yielding
iodine. The iodine, hydroiodic acid and quinine sulphate then combine to form a compound
called ‘herapathite or iodosulphite of quinine’.(1M)
Example: (1M)
Rx
Quinine sulphate…………1.5 g
Dil. Sulphuric acid ………4.0 ml
Potassium iodied ………8.0 ml
Water ……………………..200ml
Procedure: (1MK)
Dissolve quinine sulphate in dil sulphuric acid in little quantity of water
Separately dissolve potassium iodide in half quantity of water
Mix the two solutions and make up the volume
Dispense the preparation for three days and if required more call for refill.
 INCOMPATIBILITY

Q.13: What is physical incompatibility? Explain why physical incompatibility occurs due to
liquefaction
When two or more than two substances are combined together, a physical change takes place and
an unacceptable product is formed. Physical incompatibility is usually due to immisibility,
insolubility, precipitate formation or liquefaction of solid material.
Liquefaction: When certain low melting point solids are mixed together they form a new
chemical compound which has melting point lower than room temperature, therefore they
become liquid at room temperature.
Rx
Menthol --------------------------- 5g.
Camphor -------------------------- 5g.
Ammonium chloride ------------ 30g.
Light magnesium carbonate ---- 60g.
Send five powders
The combination forms eutectic mixture The substance can be dispensed by any one of the
following methods;
i) Triturate together to form liquid and mixed with an absorbent like light kaolin or light
magnesium carbonate to produce free flowing powder.
II) The individual medicaments are powdered separately and mixed with absorbent and then
combined together lightly and filled in suitable container

Q.14.: Point out the incompatibility and suggest suitable remedy.

Rx
Sodium salicylate …………..5gm.
Syrup of lemon ……………. 20 ml.
Water to make …………….. 75 ml.
Ans:
In above prescription syrup of lemon contain citric acid which react with sodium salicylate and
form salicylic acid which is a indiffusible solid, therefore substitution should be done with syrup
and lemon tincture which will serve the purpose of lemon syrup because lemon syrup is added
for sweetening & flavouring purpose and it will form a clear mixture and not affect the
therapeutic property of the mixture.