It may be defined as when several ingredients are mixed together, they may interact with each other so that an undesirable product is formed which alter or affect the appearance effectiveness & safety of the preparation.
When two or more substances are combined together, a physical change takes place and an unacceptable product is formed.
a. Insolubility: It is due the substances are insoluble in vehicle.
Method to overcome: Suitable vehicle may be taken or by adding of suspending agent.
b. Immiscibility: This is due to immiscible nature of two liquids.
Ex: Oil in water, Chloroform in water
Method to overcome: By adding suitable emulsifying agent.
c. Precipitation: Resins are in soluble in water & forms precipitate which is indiffusible.
Method of overcome: This may be corrected by the adding of a suspending agent such as tragacanth which helps to suspend the precipitation.
d. Lequification: This is due to the formation of a liquid when two solids such as phenol, thymol, menthol, camphor etc. are mixed together. It causes instability in the preparation & in the presence of moisture various micro-organisms can attack fast.
Method of overcome: To overcome this powders such as light kaolin or MgCo3 which can absorbed moisture are mixed to maintain the free flowing property of the preparation.
Chemical incompatibility may be a result of chemical interactions between the ingredients of a prescription and harmful or dangerous products may formed. It is divided into two groups.
A. Tolerated incompatibility: The chemical interaction can be minimised by changing the order of mixing or mixing the solutions in dilute forms but no alteration is made in the formulation.
Ex: Strychnine HCL with Aromatic spirit of ammonia.
Rx Strychnine HCl Solution
Aromatic spirit of Ammonia
Type: Chemical Incompatibility
Alkaloid salts with alkaline substances
Strychnine HCl is alkaloidal salt. Aromatic sprit of ammonia is alkaline substances strychnine HCl is reacts with Aromatic spirit of ammonia & produces free alkaloid which is insoluble in water.
Label: Shake will before use.
B. Adjusted incompatibility: This type of incompatibility is prevented by the addition or substitution of ingredients which does not affect the therapeutic action.
Ex: Sodium salicylate & lemon syrup by mixing these two salicylic acid is ppt out it is in-diffusible. It is corrected by compound tragacanth powder.
Rx Sodium salicylate
Type: Chemical incompatibility-soluble salicylates with acid
Incompatibility: Lemon syrup contains citric acid. It decomposed sodium salicylates into salicylic acid it is indiffusible.
How to Overcome: Lemon syrup prescribed as flavouring & sweetening agent. Hence it can be replaced by simple syrup & tincture lemon. (95% syrup 6% tincture lemon).
Other examples for Chemical Incompatibility:
1. Quinine sulphate, sodium salicylate with water:
Rx: Quinine HCl
Incompatibility: Quinine HCl is an alkaloidal salt. It reacts with sodium salicylate & quinine salicylate is precipitated out. It is an indiffusible.
How to Overcome: This type of incompatibility can be prevented by adding suspending agent like compound tragacanth powder. (2 g /100 ml) to the indiffusible substance. It is triturated in the mortor & added liquid ingredients & then soluble ingredients then dispensed.
Label: Shake will before use
2. Quinine sulphate, KI, H2SO4 & water. Iodides & bromides reacts with quinine SO4, H2SO4 & H2O (Herapathite):
Incompatibility: It is a chemical incompatibility, dilute H2So4 is used to dissolve quinine sulphate when freshly prepared it is clear. But after 3 days the reaction takes place as follows.
Dil H2So4 reacts with potassium iodide & liberate hydro iodic acid. This is partly oxidized by dil H2So4 & free iodide is liberated.
Hydro-iodic acid, iodide & quinine So4 combined together & from a compound known as
“Herapathite” it is deposits as olive green scale. It is un-desirable.
How to Overcome: About 3 days use, they may be used dispensed together. More than 3 days Kl is dispensed in one bottle ingredients are dispensed in another bottle separately. These ingredients are mixed together when-ever required.
3. Sodium salicylates with quinine sulphate, H2So4 7 H2O:
Type: Chemical incompatibility of soluble salicylate with acid.
Incompatibility: Dil H2So4 is prescribed to dissolve quinine sulphate. But dil H2So4 decomposed sodium salicylic acid, which is indiffusible.
Overcome: Suspending agents like compound tragacanth powder (2g/100ml) is added
Label: shake well before use.
4. Sodium salicylate with caffeine citrate:
Rx: Sodium salicyalate -1.0g
Caffeine citrate -0.5g
Water up to -30ml
Type: Chemical incompatibility – Soluble salicylates with acid
Incompatibility: Caffeine citrate is a mixture of equal weights of caffeine & citric acid. Caffeine is week base & caffeine citrate is acidic in nature. The citric acid present in caffeine liberates salicylic acid which gets precipitated, which is indiffusible.
Overcome: Caffeine citrate is substituted by caffeine half its quantity. It reduces acidic reaction though caffeine is insoluble compound. Hence the mixture is clean.
5. Sodium salicylate with ferric salt with water:
Rx: Sodium salicylate
Type: This is chemical incompatibility- salicylate with ferric salts.
In this soluble salicylates reacts with ferric salts. Sodium salicylate reacts with ferric chloride and produces ferric salicylate which is precipitated out. It is indiffusible.
How to overcome: It is dispensed by using a suspending agent like compound tragacanth 2%.
Label: “Shake well before use”
6. Sodium salicylate NaHCO3 & Water:
Rx: Sodium salicylate
Sodium meta bisulphate
Type: Chemical incompatibility – solublesalicylates with alkali.
Incompatibly: The solution become dark in colour due to alkali catalyzed conversion of salicylate to quinoid form.
Overcome: So anti-oxidant-sodium meta bisulphate is added to prevent darkening of preparation.
7. Incompatibility of causing evolution of Co2:
Ex: Sodium bicarbonate with borax
Rx: Sodium bicarbonate
Type: Incompatibility of causing evaluation of Co2
When borax is dissolved in water oxidation reaction takes place & produces boric acid Boric acid reacts with glycerine & form mono-basic glycerine boric acid. This reacts with NaHCo3 liberating Co2 from the NaHCo3.
Overcome: All the ingredients should be mixed with water in an open vessel until the effervescence stops. If the reaction is slow hot water is added to fasten the reaction.
When certain drugs are administered to the patient for a particular therapy but it produce effects other than that for which it is administered. Here the nature & intensity of action may be different from what it is expected.
Causes: Adverse reaction, Allergic reaction, Drug dependence (drug addiction),Drug tolerance, Drug resistance, Idiosyncrasy
Types of incompatibility:
1. Synergism: It refers to the effects of combined drugs in which the one drug tends to increase the pharmacological action of other drug or prolong the duration of action of another drug.
Ex: Phenobarbitone, sodium with Na salicylate
Rx: Phenobarbitone sodium
In this prescription phenobarbitone sodium & sodium salicylate minimum per dose. But combined action of these two ingredients is greater than the sum of their individual action with minimum dose, the maximum efficacy is obtained.
2. Antagonism: When two drugs possessing opposite actions, are prescribed in the same prescription is known as antagonism. So any one of the drug is omitted.
Ex: Phenobarbitone sodium with Ephedrine HCl.
Rx: Phenobarbitone sodium
Syrup Chloroform water
In this prescription, ephedrine Hcl is prescribed to prevent bronchial spasm in asthma. It also has the stimulant action as the cerebrum & respiratory centre. Pheno-barbitone sodium combined with ephedrine Hcl to overcome. Their stimulation it is an antagonistic combination.
3. Contraindication: The use of certain drugs which may be contra indicated in a Particular disease or a Particular patient who is allergic to it.
Ex: Barbiturates & Morphine in Asthma.
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