Pharmaceutical Incompatibility

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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)



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.



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.



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.

Pharmaceutical Incompatibility

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