Chemical & Physical Incompatibility in Prescription

INCOMPATIBILITY, Prescription, pharmacy notes, EXIT Exam


Incompatibility occur as a result of mixing two or more antagonistic substances.  An undesirable product is formed which affect the safety, efficacy and appearance of pharmaceutical preparation.

For Example, the interaction of that comes under incompatibilities includes

  • Drug with additives
  •  drug with other drug
  • Additives with additives
  • Dosage error

Incompatibilities may occur

  • During compounding and dispending
  • During manufacturing
  • Packaging or
  • Administration of drugs

Types of Incompatibilities     

(A) Physical Incompatibilities

(B) Chemical Incompatibilities

(C) Therapeutic Incompatibilities

(A) Physical Incompatibilities

When two or more substances are combined together, a physical change (like Immiscibility , insolubility, precipitation,  liquefaction) takes place and an unacceptable product is formed.

Interaction between two or more substances which may lead to change in color, odor, taste, viscosity etc.

Physical Incompatibilities are visible  and easily corrected by applying pharmaceutical skill.

Physical incompatibility con be corrected by

  1. Change the order of mixing
  2. Emulsification
  3. Addition of suspending agent
  4. Change in form of ingredients
  5. By addition, substitution or omission of therapeutically inactive substances


 1.     Immiscibility


  • Castor oil – 15ml
  • Water upto – 60ml

Incompatibility:  Water and oil are immiscible so it is corrected by

Emulsifying   agent is used to make water & Oil miscible .

  2.  Insolubility :-


  • Ephednine sulphate – 0.25g
  • Menthol- 0.02ml
  • Liquid paraffin upto -30ml

Ephedrine sulphate is not soluble in liquid paraffin  so Ephedrine is substituted with Anhydrous Ephedrine (soluble in liquid paraffin)

 3. Precipitation :-  


  • Tincture benzoin compound- 5.0ml
  • Glycerine- 15.0ml         
  • Rose water upto -100ml  

 Tincture benzoin contain  resins & upon changing solvent result into precipitation. To eliminate this type incompatibility, addition of tincture benzoin with rapid stirring to yield a fine colloidal dispersion.

 4.  Liquefaction


  • Menthol –   5g
  • Camphor –  5g
  • Ammonium chloride  -30g   
  • Light magnesium carbonate – 60g

Menthol + Camphor + Ammonium chloride, get  liquefied  on mixing so Add light magnesium carbonate   to  get free flowing powder.

(B) Chemical Incompatibility

  • Chemical incompatibility result due to chemical interaction b/w ingredients to form toxic or inactive product.
  • So while dispensing such prescription, either prevent formation of harmful product or correct them & inform the prescriber.

Types of Chemical incompatibilities

Minimised by changing the order of mixing or mixing solution in dilute form No alteration made in formulaIncompatibility is prevented by addition or substitution on one of the reacting ingredient with another equal therapeutic value.

Chemical Incompatibility may be Intentional or Unintentional.

When prescriber prescribe knowingly prescribed incompatible drugsWhen prescribed without knowing the incompatibility

(C) Therapeutic Incompatibility

Therapeutic Incompatibility may result of prescribing drugs for specific degree of pharmacological action but nature or intensity of the action different from the intended by the prescriber.

THERAPEUTIC INCOMPATIBILITY (based on MECHANISM) is divided into two groups.

1. Pharmacokinetic: It involves the effect of a drug on another from the point of view that includes absorption, distribution, metabolism and excretion.

2. Pharmacodynamics: These are related to the pharmacological activity of the inter-acing drugs. Example-Synergism, antagonism, altered cellular transport, effect on the receptor site.

Therapeutic Incompatibility occurs due to

  1. Error in dosage
  2. Wrong drug or dosage form
  3. Contra-indicated drugs
  4. Synergistic or antagonistic drugs
  5. Drug interaction

i) Error in Dosage


  • Atropine Suphate- 0.006 g
  • Phenobarbitione- 0.015 g
  • Aspirin- 0.300 g

Quantity of Atropine Suphate is more than maximum dose. So Pharmacist should referred back to prescriber for correction.

ii) Wrong Dose or Dosage form

Certain drugs have quite similar name so there is a danger of dispensing the wrong drug by pharmacist.

  • Prednisone & Prednisone
  • Digoxin & Digitoxin

iii) Contra-indicated Drugs

There are certain drugs which may be contra- indicated in a particular disease or a particular patient who is allergic to it.


  • Corticosteroids are contra-indicated in the patients having peptic ulcers


  • Sulphadiazine 250 mg
  • Sulphamerazine 250 mg
  • Ammonium chloride 500 mg
  • Ammonium Chloride- Urinary Acidifier- cause deposition of Sulphonamide crystal in Kidney si prescription referred back to Physician.

iv) Synergistic or antagonistic drugs

  • When two drugs are prescribed together, they tend to increase the activity of each other which is known as SYNERGISM.
  • When two drugs are prescribed together, they tend to decrease the activity of each other which is known as ANTAGONISM



  • Acetyl Salicylic acid- 0.6 g
  • Probenecid- 0.5 g
  • Both are used to treat goat but combination lead to neutralization of action-Antagonism.
  • A combination of aspirin and paracetamol increases the analgesic activity- Synergistic

v) Drug Interaction

The effect of one drug is altered by the prior or simultaneous administration of another drug. The drug interaction can usually be corrected by the proper adjustment of dosage if the suspected interaction is detected.

Example: Tetracycline capsule – 250mg capsules ; Direction: Take one capsule every 6 hours with milk. Causes:-Tetracycline is inactivated by calcium present in milk.

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