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Pharmaceutical Incompatibility 1www.pharmgb.org II
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Asif Hasan NiloyGB Pharm24 (3rd Semester)
Pharmaceutical Incompatibility: A pharmaceutical incompatibility
may be defined as theresult of prescribing or mixing the substances
which are antagonistic in nature and anundesirable product is
formed which may affect the safety, purpose or appearance of
thepreparation. 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 arecombined together, a physical change takes
place and an unacceptable product isformed.
Correction: Since these changes which take place are usually
visible therefore they canbe easily corrected by applying the
pharmaceutical skill to obtain an acceptablepreparation.
Example with solution: oils and water are immiscible with each
other. They can bemade miscible by emulsification, e.g., castor oil
emulsion, olive oil emulsion, lliquidparaffin etc.
RxOlive oil 30mlWater up to 120mlMake an emulsion.Type:
Therapeutic incompatibility.
Solution: in this preparation, olive oil (a fixed oil) is
immiscible with water. To makethem miscible, an emulsifying agent
will have to be incorporated.
Chemical Incompatibilities: Chemical incompatibilities are those
in which a chemicalreaction takes place between the ingredients and
a new undesirable compound isformed.
Correction: These types of incompatibilities are little
difficult to correct and in somecases 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 andstore in suitable containers, in such cases the physician
should be consulted and informed.
Example:1. Rx
Strychnine hydrochloride solution 6mlAromatic spirit of ammonia
4mlWater 120mlMake a mixture.
Type: Physical incompatibility (incompatibility of alkaloidal
salts with alkaline substances)
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Pharmaceutical Incompatibility 2www.pharmgb.org II
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Asif Hasan NiloyGB Pharm24 (3rd Semester)
2. Morphine The solubility of morphine is 12 minimum per ounce.
Thereforepreparation containing less than 12 minimum per ounce of
morphine will notprecipitated with alkaline substances. Further
morphine is more soluble in alcohol thanwater. Therefore a mixture
containing sufficient alcohol morphine will not beprecipitated even
more than 12 minimum per ounce is precipitated along with
alkalinesubstances.
Types: The chemical incompatibilities fall into two groups:(a)
ToleratedIn tolerated incompatibilities, where practicable the
reaction is minimized by applyingsome suitable order of mixing or
mixing the solutions in dilute forms but no alternation ismade in
the active indigents of the preparation.
(b) AdjustedIn adjusted incompatibilities the reaction is
prevented by addition or substitution of oneof the reacting
substances with another of equal therapeutic value but does not
affect themedicinal 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 prescribingcertain drugs to the patient with the
intention to produce a specific degree of action butthe nature or
the intensity of the action produced is difficult from that
intended by theprescriber. 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 RxCodeine phosphate 0.6gmMake powders, send such 10
powders.Type: Therapeutic incompatibility.
In the present prescription an overdose of codeine phosphate has
been prescribed.Therefore, the prescription must be referred back
to the prescriber.
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Pharmaceutical Incompatibility 3www.pharmgb.org II
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Asif Hasan NiloyGB Pharm24 (3rd Semester)
RxTetracycline hydrochloride 250mgMake 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 ispresent in milk. Therefore,
tetracycline capsules should not be taken with milk.
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Intentional incompatibility: The drugs i.e. Acetophenatidin and
Acetyl salicylic acid areanalgesic. Acetophenatidin is CNS
depressant whereas caffeine is CNS stimulant, whichneutralizes the
side effect of Acetophenatidin. This is an Intentional
incompatibility.
Example RxAcetophenatidin 150mgAcetyl salicylic acid
200mgCaffeine 40mgMake capsules, send such 10 capsules.Type:
Therapeutic incompatibility (Intentional)
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Diffusible Precipitates: The reaction between the dilute
solutions proceed at a slow rateand the precipitates formed are
light and diffuse readily in the solution.
Method A is used when diffusible precipitates are formed and
they form very smallportion of the mixture.Divide the vehicle into
two equal portions. Dissolve one of the reacting substances in
oneportion and the other in the other portion. Mix the two portions
by slowly adding oneportion to the other with rapid stirring.
Indiffusible Precipitates: The reaction between strong solutions
proceed at a faster rateand 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 appreciableportion of the mixture.
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Asif Hasan NiloyGB Pharm24 (3rd Semester)
Divide the vehicle into two equal portions. Dissolve one of the
reacting substances in oneportion Place the other portion of the
vehicle in a mortar, to this incorporate a suitableamount of
compound tragacanth powder with constant trituration until a
smoothmucilage is produced, then add and dissolve the other
reacting substances. Mix the twoportions by slowly adding one
portion to the other with rapid stirring.
The precipitates so formed may be diffusible or indiffusible if
the reacting substancesshould be diluted to the maximum extent
before mixing them.