The document provides an overview of drug incompatibility, which is defined as the undesirable effects resulting from mixing incompatible substances, impacting the safety and efficacy of pharmaceutical dosage forms. It categorizes incompatibilities into physical, chemical, and therapeutic types, with detailed examples and methods for correction. Emphasis is placed on identifying and addressing issues like dosage errors, mixture incompatibility, and the need for caution in prescription practices.

1. Prof. Vaishali P. Argade
Lecturer in PRES, Institute of Pharmacy, Loni
Email:vaishali.argade@pravara.in
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2. Learning Outcomes
After completion of this video, you will be able to:
1. Understand the concept of Incompatibility
2. Understand the reasons of Incompatibility
3. Classify the Incompatibility
4. Understand the concept of Physical, chemical & therapeutic
Incompatibility with example.
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3. Definition
• Incompatibility is an undesirable result of mixing of two or
more antagonistic substances which may affects the safety
efficacy and appearance of the pharmaceutical dosage forms.
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4. Incompatibility may be due to
• Drug-Drug Incompatibility
1st Drug + 2nd Drug
Mixed
Undesired / unwanted Product
Drug-Drug Incompatibility
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5. Incompatibility may be due to
• Drug Excipient Incompatibility
Drug + Excipients
Mixed
Undesired / unwanted Product
Drug Excipient Incompatibility
5

6. Incompatibility may be due to
• Dosage Error Incompatibility
Example:
Rx
Codeine Phosphate 5 g
Prepare 10 powders
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Rx
Codeine Phosphate 5 mg
Prepare 10 powders
Correct
Prescription
Dosage Error
Incompatibility

7. • Incompatibility may occur not only during compounding &
dispensing but also at any stage during formulation,
Manufacturing, Packaging & administration of drugs.
• Now a days the prescription are generally written for the
official (generic) or proprietary(Trade/Brand) names which are
manufactured by pharmaceutical companies.
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8. Types of Drug Incompatibility
1. Physical incompatibility
2. Chemical incompatibility
3. Therapeutic incompatibility
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9. Definition Physical Incompatibility
• When two or more than two substances combined together a physical
changes take place and an undesirable product is formed it is called as
physical incompatibility.
• It is due to insolubility, immiscibility, precipitation, liquefaction of solid
materials.
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10. General methods of Correction of Physical
Incompatibility
1. Change the order of mixing of ingredients in prescription
2. By Emulsification
3. Addition of suspending agents
4. Change in the forms of ingredients
5. By addition, substitution or Omission of therapeutically inactive
substances
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11. Example of Physical Incompatibility with there methods
of correction
Example 1: Immiscibility
Rx
Castor Oil 15ml
Water up to 60ml
Make an Emulsion
In this prescription castor oil & water are immiscible with each other.
To overcome this incompatibility an emulsifying agents is used to make a good
emulsion.
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12. .
Example 2:Insolubility
Insolubility means the inability of material to dissolve in a particular solvent.
Majority of Physical incompatibility are due to Insolubility of organic or
inorganic compounds in to a particular solvent.
Some solids are insoluble in solvent there are of two types:
A) Diffusible Solids
B) Indiffusible Solids
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13. A) Diffusible Solids: These are insoluble in water but get evenly distributed on
shaking throughout the liquid for sufficient long time.
Eg: Magnessium carbonate
B) Indiffusible Soilds: These are insoluble in water but do not get evenly
distributed on shaking throughout the liquid for sufficient long time, So
Suspending agents are incorporated.
This suspending agents increases the thickness of the preparation and
maintained the uniform distribution of insoluble substances.
Eg: Chalk powder, Acetyl salicylic Acid, Phenacetin, Zinc Oxide & Calamine
etc.
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14. Incase of Indiffusible solids Two types of suspending agents are added,
a) Compound Tragacanth Powder ( 2g/100ml), CTP:
It is used when vehicle is other than water or Chloroform water
b) Tragacanth Mucilage (1/4th of it’s total volume), TM:
It is used when vehicle is Water or Chloroform water
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15. Rx
Phenacetin 3g
Caffeine 1g
Orange Syrup 12ml
Water up to 90ml
Make a Mixture
In this prescription Phenacetin is a indiffusible substances so, suspending
agents are used to make a stable mixure.
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16. Example 3: Precipitation
• When the drug is insoluble in the vehicle it may be precipitated
• Eg: Resins are insoluble in Water
When tincture containing resinous matter is added in water , resins
agglomerated forming indiffusible precipitate.
Rx
Tincture benzoin compound 5ml
Glycerine 15ml
Rose water up to 100ml
Tincture benzoin compound contain resins which may be
precipitated when combined with water. So addition of tincture with rapid
stirring yields a fine colloidal dispersion. So there is no need of suspending
agent.
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17. Example 4: Liquefaction
When certain low melting points solids (Ex: camphor, Phenol, Menthol,
Thymol, Chloral hydrate, Aspirin) are mixed together a liquid or semisolid
mass is formed known as Eutectic mixture.
This is due to lowering of melting points of the mixture to below room
temperature.
This types of substances create problems when they are dispense in powder
form so, such types of substances can be dispensed as follows:
1. Dispense a separate powder
2. Low melting point substances triturate together to form a liquid. Add
absorbent like light kaolin or light magnesium carbonate to produce a free
flowing powder.
3. The individual medicament weigh separately & mixed with absorbent
lastly combined together then filled in to a suitable container.
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18. Rx
Menthol 5g
Camphor 5g
Ammonium Chloride 30g
Light Magnessium Carbonate 60g
Make an insufflation
In this prescription Menthol, Camphor & Ammonium Chloride get
liquefied on mixing with each other. To dispense this prescription Menthol,
Camphor & Ammonium Chloride are triturate together to form a liquid. Add
light magnesium carbonate & mixed it thoroughly to make a free flowing
powder.
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19. 2. Definition Chemical Incompatibility
• When two or more than two substances combined together a Chemical
interactions take place and an undesirable product is formed it is called as
chemical incompatibility.
• Types of Chemical Incompatibility
1. Tolerated: In this type, the chemical interaction can be minimize by
changing the order of mixing but not alteration made in the formulation.
2. Adjusted: In this type, the chemical interaction can be minimize by
addition or substitution of one of the reacting substance with another of
equal therapeutic value.
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20. The Chemical Incompatibility is may be due to;
1. Intentional:
When the prescriber knowingly prescribe the incompatible drugs is called
the intentional chemical incompatibility.
2. Un-Intentional:
When the prescriber Unknowingly prescribe the incompatible drugs is
called the Un-intentional chemical incompatibility.
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21. Precipitate Yielding Interactions
There are two methods for dispensing of diffusible & indiffusible solids;
1. Method A:
2. Method B:
1. Method A: Use when diffusible precipitate is formed.
Divide the vehicle in to two equal portion. Dissolve one of the
reacting substance in one portion of the vehicle & second reacting substance
with second portion of the vehicle. Lastly slowly add one portion in to the
another with rapid stirring.
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Fig. 1: Flow chart for explaining Method A
Rx
Sodium hydroxide 2g
Sodium chloride 2g
Water q.s. 100ml

22. 1. Method B:
Use when Indiffusible precipitate is formed.
Divide the vehicle in to two equal portion. Dissolve one of the reacting substance
in one portion of the vehicle. Weight a suitable quantity of Compound tragacanth
powder/ Tragacanth Mucilage & transfer in to mortar, to it add second portion of the
vehicle to produce smooth mucilage then add second reacting substance. Lastly mixed
two portion by slowly adding one portion in to the another with rapid stirring.
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Fig. 2: Flow chart for explaining Method B
Rx
Sodium hydroxide 2g
Sodium chloride 2g
Water q.s. 100ml

23. Example of chemical incompatibility with there
methods of correction
1. Alkaloidal Incompatibility
a) Alkaloidal salts with alkaline substances
b) Alkaloidal salts with soluble iodides
c) Alkaloidal salts with Tannins
d) Alkaloidal salts with Salicylates
e) Alkaloidal salts with soluble iodides & Bromides
2. Soluble Salicylate incompatibility
a) Soluble salicylate with ferric salts
b) Soluble salicylate & benzoate with acid
c) Soluble salicylate with Alkali bicarbonates
3. Soluble iodides incompatibility
a) Oxidation of iodides with ferric salts
b) Oxidation of iodides with Potassium chlorate
c) Oxidation of iodides with Quinine Sulphate
4. Chemical Incompatibility causing evolution of carbon dioxide
a) Sodium bicarbonates with soluble calcium & magnesium salts
b) Sodium bicarbonates with soluble calcium & magnesium salts
5. Miscellaneous chemical incompatibility
a) Potassium Chorate with Oxidisable Substances:
b) Soluble barbiturate with ammonium bromide
c) Incompatibility of Liquorice Liquid extract
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24. 1. Alkaloidal Incompatibility
a) Alkaloidal salts with alkaline substances
Alkaloids are very slightly soluble in water where as alkaloidal
salts are soluble in water. When this alkaloidal salts are reacts with alkaline
substances Diffusible precipitate is formed. Hence follows method A for
precipitate yielding interaction.
Rx
Strychnine Hydrochloride solution 6ml
Aromatic sprit of Ammonia 4ml
Water up to 120ml
Make a Mixture
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25. 25
Fig. 3: Flow chart for explaining example using Method A

26. b) Alkaloidal salts with Soluble iodide
Eg: When Strychnin is prescribe with pottassiun iodide insoluble hydroiodide
is formed which is diffusible ppt Hence follow methods A for ppt. yielding
interactions.
C) Alkaloidal salts with Tannins
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27. d) Alkaloidal salts with Salicylates
Example
Rx
Quinine Hydrochloride 0.12g
Sodium Salicylate 4 g
Water up to 100ml
Make a Mixture
In this Prescription,
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28. 28
Fig. 4: Flow chart for explaining example using Method B

29. e) Alkaloidal salts with soluble iodides & Bromides
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Hence follows method A for precipitate yielding interaction

30. Rx
Potassium iodide 1.5g
Tincture of Stramonium 8.5 ml
Chloroform Water 100ml
In this prescription Tincture of Stramonium combined with
Potassium iodide it will formed a diffusible ppt. of hydroiodides so follow
method A for Precipitate yielding interactions
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31. 31
Fig. 5: Flow chart for explaining example using Method A

32. Example
Rx
Quinine Sulphate 1.5g
Dilute Sulphuric Acid 4 ml
Patassium iodide 8 g
Water q.s. 200ml
In this Prescription
Dilute the Dilute Sulphuric Acid with 100 ml of water & dissolved
Quinine Sulphate in it. Patassium iodide is dissolved in remaining quantity of
water & mixed with the first portion. The mixture formed is point clear at first
time but after about 3 days it may deposit bronze or olive green scale due to
herapath reaction for quinine.
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33. 2. Soluble Salicylate incompatibility
a) Soluble salicylate with ferric salts
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Example
Rx
Ferric Chloride Solution 2ml
Sodium Salicylate 3g
Water q.s. 90ml
Make a Mixture
In this Prescription

34. b) Soluble salicylate & benzoate with acid
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Example
Rx
Sodium Salicylate 3 g
Syrups of Lemon 15ml
Water q.s. 60ml
Make a Mixture
In this Prescription Syrup of lemon contains citric acid when it react with
Sodium Salicylate it gives Salicylic Acid as indiffusible ppt. To correct
this follows method B for precipitate yielding interactions or replace the
lemon syrups with simple syrups.

35. c) Soluble salicylate with Alkali bicarbonates
Soluble salicylate & Alkali bicarbonates combined together, it
absorb the atmospheric oxygen & become reddish brown in color this color
change does not affect the therapeutic value but may leads to confusion in the
mind of patient. To avoid such confusion antioxidants like sodium
metabisulphite is added with permission of the doctor.
Example
Rx
Soluble salicylate 8g
Sodium bicarbonates 8g
Sodium Metabisulphite 0.08g
Chloroform Water q.s. 120ml
Make a Mixture
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36. 3. Soluble iodides incompatibility
a) Oxidation of iodides with ferric salts
When ferric salts reacts with soluble iodides it get converted in to ferrous salt.
To prevent this incompatibility , the prescriber may substitute ferric salts with
iron & ammonium citrate. Ultimately the iron is converted in to an organic
compound which does not yield ferric ions.
b) Oxidation of iodides with Potassium chlorate
When soluble iodides reacts with Potassium chlorate free iodine is liberated.
To prevent this incompatibility the two reacting substance dispensed
separately.
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37. c) Oxidation of iodides with Quinine Sulphate
Quinine Sulphate is not freely soluble in water, to make it soluble dilute
Sulphuric acid is used.
These Sulphuric acid liberates hydriodic acid from patassium iodide.
Hydriodic acid is partially oxidized by Sulphuric acid & gives iodine.
The iodine, hydriodic acid & Quinine Sulphate then combined to formed a
compound called as Herapathite or Iodosulphite of quinine.
The compound has following chemical formula:
( C20 H24O4 N2) . 3H2 S O4 . 2HI. 2I2 . 6H20
The mixture formed is clear at first but after about 3 days it may deposit
bronze or olive green scale due to herapath reaction.
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38. These incompatibility can be removed by one of the following methods;
1. Refer the prescription back to the prescriber
2. Supply the preparation sufficient for about 3 days only.
3. In case the patient required the mixture for more than three days both the
solutions are supplied in the separate bottle.
4. Tell the patient regarding bronze or olive green color change.
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39. Example
Rx
Quinine Sulphate 1.5g
Dilute Sulphuric Acid 4 ml
Patassium iodide 8 g
Water q.s. 200ml
In this Prescription
Dilute the Dilute Sulphuric Acid with 100 ml of water & dissolved
Quinine Sulphate in it. Patassium iodide is dissolved in remaining quantity of
water & mixed with the first portion. The mixture formed is point clear at first
time but after about 3 days it may deposit bronze or olive green scale due to
herapath reaction for quinine.
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40. 4. Chemical Incompatibility Causing Evolution of
Carbon dioxide
When carbonates and bicarbonates are dispensed in the presence of
acidic drugs they react together with evaluation of carbon dioxide. If the
reaction is not allowed to complete there may be a chances of bursting of the
bottle. To prevent these bursting, the reaction must be completed before
transferring the mixture in to dispensing bottle. Hot water can also be use to
increased the rate of reaction.
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41. a) Sodium bicarbonates with soluble calcium & magnesium salts
When Sodium bicarbonates combined with soluble calcium &
magnesium salts, due to double decomposition reaction carbon dioxide is
formed along with insoluble carbonates which is a diffusible ppt.
These reaction is slow at room temperature so use hot water to
increase the rate of reaction. This mixture is dispensed when effervescence is
ceased. The precipitation of carbonate formed are diffusible in nature hence
follow method A for precipitate yielding interactions.
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42. b) Bismuth subnitrate with sodium bicarbonate
Bismuth subnitrate when combined when combined with sodium
bicarbonate in the presence of water, carbon dioxide gas is liberated due to the
following reaction.
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43. 5. Miscellaneous Chemical Incompatibility
a) Potassium Chorate with Oxidisable Substances:
When potassium chlorate is prescribed along with
oxidisable substances charcoal, sulphur sugar organic compound or any
oxidisable substance, during dispensing if heating /trituration is done
there are chances of explosion.
To avoid this ingredients should be powdered separately in
dry mortar & mix gently with clean spatula on ointment tile,without
any friction.
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44. b) Soluble barbiturate with ammonium bromide
When Soluble barbiturate combined with ammonium bromide
in the presence of water the baritone is separated as indiffusible precipitate
which are insoluble in water. Hence follow method B for precipitate yielding
interaction.
C) Incompatibility of Liquorice Liquid extract
Liquorice Liquid extract is used as a flavouring agent. The
flavouring property is due to glycerrhizine which is a mixtue of potassium &
calcium salts of glycerrhizinic acid. The acid decomposes & formed a
diffusible ppt.
Hence follow method A for precipitate yielding interaction or
the prescription may referred back to the prescriber for the change of flavoring
agent.
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45. Definition 3. Therapeutic Incompatibility
Therapeutic Incompatibility may be a result of prescribing
certain drugs to produces a specific degree of pharmacological
action but the nature or intensity of action produced is different
from that intended by the prescriber.
Therapeutic Incompatibility may be due to following reasons:
1) Error in dosage
2) Wrong name or dosage form
3) Contra-indicated drugs
4) Synergistic & Antagonistic drugs
5) Drug Interaction
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46. 1. Error in dosage:
It is the most serious type of error in dispensing so, it is the duty of pharmacist
to check the prescription before dispensing.
Rx
Codeine Phosphate 0.5 g
Prepare 10 powders
This is an example of over dosage. The intension of physician may be to
prescribe 5 mg but he has given 0.5 g (500mg). In this case refer the
prescription back to the prescriber for correction of over dosage of Codeine
phosphate.
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47. 2. Wrong name or dosage forms:
Certain drugs have quite similar names like Prednison &
prednisolon, Digoxin & Digitoxin so it may create a problem during
dispensing.
Many times drugs are available in different dosage forms and hence
it is necessary to mention the dosage forms of a drugs.
3. Contra-indicated drugs
Certain drugs are contraindicated in particular patient whom are allergic to it.
Eg: Penicilline & Sulpha drugs are contraindicated in patients who are allergic
to it. So in this case refer prescription back to the prescriber for correction.
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48. 4. Synergistic & antagonistic drugs
Synergism:
Example
Rx
Amphetamine Sulphate 20mg
Ephedrine sulphate 100mg
Syrups q.s. 100ml
Make a Mixture
In this combination Amphetamine sulphate & Ephedrine sulphate
are sympathomimetic drugs so there is need to reduced the dose of each drugs
or refer the prescription back to the prescriber for correction.
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49. Antagonism:
Example
Rx
Acetyl salicylic acid 0.6g
Probenicid 0.5 g
Acetyl salicylic acid & Probenicid are used in the treatment of gout but the
combination of these two drugs leads to neutralization so, refer the prescription
back to the prescriber for correction.
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50. 5. Drug Interaction
When two or more drugs are administered together effect of one drugs is
alter by the simultaneous administration of another drug.
Example
Rx
Tetracycline hydrochloride 250mg
Prepared 10 capsules
Direction:Take 1 capsule every six hour with milk
Tetracycline is inactivated by calcium which is present in milk so
tetracycline capsules should not be given with milk so, refer the prescription
back to the prescriber for correction or change the direction take 1 capsule
every 6 hours with water.
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51. References
1. Pharmaceutics II
By R. M. Mehata,
Vallabh Prakashan,
Third edition, 2010.
2. Pharmaceutics-2 (Dispensing Pharmacy)
By Dr. G.K.Jani,
B.S.shah Prakashan,
10th edition, 2011-2012.
3. Introduction to Pharmaceutics-II
By A.K.Gupta & S.S. Bajaj,
CBS Publishers & Distributors,
4th edition,2000.
4. MSBTE board Annual question paper,
https://msbte.org.in
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By- Ms. Argade V.P.

52. Thank You.....
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