Pharmaceutical Incompatibility

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Pharmaceutical Incompatibility: A pharmaceutical incompatibility may be defined as the

result of prescribing or mixing the substances which are antagonistic in nature and an
undesirable product is formed which may affect the safety, purpose or appearance of the
preparation. These incompatibilities are of three general types.
(i) Physical
(ii) Chemical
(iii) Therapeutic
Physical Incompatibilities: These are those when two or more than two substances are
combined together, a physical change takes place and an unacceptable product is
formed.
Correction: Since these changes which take place are usually visible therefore they can
be easily corrected by applying the pharmaceutical skill to obtain an acceptable
preparation.
Example with solution: oils and water are immiscible with each other. They can be
made miscible by emulsification, e.g., castor oil emulsion, olive oil emulsion, lliquid
paraffin etc.
Rx
Olive oil
30ml
Water
up to 120ml
Make an emulsion.
Type: Therapeutic incompatibility.
Solution: in this preparation, olive oil (a fixed oil) is immiscible with water. To make
them miscible, an emulsifying agent will have to be incorporated.
Chemical Incompatibilities: Chemical incompatibilities are those in which a chemical
reaction takes place between the ingredients and a new undesirable compound is
formed.
Correction: These types of incompatibilities are little difficult to correct and in some
cases it may be necessary to eliminate or substitute one of the reacting substances,
dispense them in separate containers, change them to non-reactive form or to pack and
store in suitable containers, in such cases the physician should be consulted and informed.
Example:
1. Rx
Strychnine hydrochloride solution
6ml
Aromatic spirit of ammonia
4ml
Water
120ml
Make a mixture.
Type: Physical incompatibility (incompatibility of alkaloidal salts with alkaline substances)

Asif Hasan Niloy

GB Pharm24 (3rd Semester)

Pharmaceutical Incompatibility
www.pharmgb.org II www.facebook.com/gono.Bharm24

2. Morphine The solubility of morphine is 12 minimum per ounce. Therefore

preparation containing less than 12 minimum per ounce of morphine will not
precipitated with alkaline substances. Further morphine is more soluble in alcohol than
water. Therefore a mixture containing sufficient alcohol morphine will not be
precipitated even more than 12 minimum per ounce is precipitated along with alkaline
substances.
Types: The chemical incompatibilities fall into two groups:
(a) Tolerated
In tolerated incompatibilities, where practicable the reaction is minimized by applying
some suitable order of mixing or mixing the solutions in dilute forms but no alternation is
made in the active indigents of the preparation.
(b) Adjusted
In adjusted incompatibilities the reaction is prevented by addition or substitution of one
of the reacting substances with another of equal therapeutic value but does not affect the
medicinal action of the preparation. The incompatibility may be
(i) Intentional when the prescriber knowingly prescribes the incompatible drugs.
(ii) It may be unintentional when the prescriber prescribes the drug without
knowing that there is incompatibility in the prescribed drugs.
Therapeutic Incompatibility: Therapeutic incompatibility may be the result of prescribing
certain drugs to the patient with the intention to produce a specific degree of action but
the nature or the intensity of the action produced is difficult from that intended by the
prescriber. It may be due to the administration of
(i) Overdose or improper dose of a single drug
(ii) Wrong dose or dosage form
(iii) Contraindicated drugs
(iv) Synergistic or antagonistic drugs.
Example
Rx
Codeine phosphate
Make powders, send such 10 powders.
Type: Therapeutic incompatibility.

0.6gm

In the present prescription an overdose of codeine phosphate has been prescribed.

Therefore, the prescription must be referred back to the prescriber.

Asif Hasan Niloy

GB Pharm24 (3rd Semester)

Pharmaceutical Incompatibility
www.pharmgb.org II www.facebook.com/gono.Bharm24

Rx
Tetracycline hydrochloride
250mg
Make capsules, send such 10 capsules.
Label: Take one capsule every six hours with milk.
Type: Therapeutic incompatibility.
In this prescription the direction is wrong. Tetracycline is inactivated by calcium which is
present in milk. Therefore, tetracycline capsules should not be taken with milk.
****
Intentional incompatibility: The drugs i.e. Acetophenatidin and Acetyl salicylic acid are
analgesic. Acetophenatidin is CNS depressant whereas caffeine is CNS stimulant, which
neutralizes the side effect of Acetophenatidin. This is an Intentional incompatibility.
Example
Rx
Acetophenatidin
150mg
Acetyl salicylic acid
200mg
Caffeine
40mg
Make capsules, send such 10 capsules.
Type: Therapeutic incompatibility (Intentional)
***
Diffusible Precipitates: The reaction between the dilute solutions proceed at a slow rate
and the precipitates formed are light and diffuse readily in the solution.
Method A is used when diffusible precipitates are formed and they form very small
portion of the mixture.
Divide the vehicle into two equal portions. Dissolve one of the reacting substances in one
portion and the other in the other portion. Mix the two portions by slowly adding one
portion to the other with rapid stirring.

Indiffusible Precipitates: The reaction between strong solutions proceed at a faster rate
and the precipitates formed are thick and do not diffuse readily in the solution.
Method B is used when indiffusible precipitates are formed and they form an appreciable
portion of the mixture.

Asif Hasan Niloy

GB Pharm24 (3rd Semester)

Pharmaceutical Incompatibility
www.pharmgb.org II www.facebook.com/gono.Bharm24

Divide the vehicle into two equal portions. Dissolve one of the reacting substances in one
portion Place the other portion of the vehicle in a mortar, to this incorporate a suitable
amount of compound tragacanth powder with constant trituration until a smooth
mucilage is produced, then add and dissolve the other reacting substances. Mix the two
portions by slowly adding one portion to the other with rapid stirring.

The precipitates so formed may be diffusible or indiffusible if the reacting substances

should be diluted to the maximum extent before mixing them.

Asif Hasan Niloy

GB Pharm24 (3rd Semester)