INCOMPATABILITIES IN PRESCRIPTION (PART 1)

INCOMPATABILITIES IN PRESCRIPTION

Hey readers, this is Sarang More a edublogger and student. This is another blog on incompatibility of prescription, please do check it as it will clear your concepts and share it to your friends and coworkers.

 PART 1

·     Sources of errors in Prescription :-

1.  Abbreviation –

Abbreviation presents a problem in understanding parts of prescription order. Extreme care should be taken by a pharmacist while interpreting the abbreviation.

Pharmacist should not guess the meaning of the ambiguous abbreviation, eg to dispense the Achromycin for “achro” may cause the difficulty when the intention of the prescriber id to dispense Achrostatin.

The abbreviation ‘SSKI’ represent the use of short hand saturated solution and chemical symbol of potassium iodide.

2.  Name of the drug :-

There are certain drugs whose name look or sound same like of other drugs. Likewise,

Digitioxin	Digioxin
Prednisone	Prednisolone
Indocin	Lincocin
Doridon	Doxidan
Parbalate	Robalate
Ananase	Orinase

 

Name of the pharmaceutical products have been changed on certain occasion due to the possible confusion with the name of other product.

3.  Strength of the product :-

The strength of the preparation should be stated by the prescriber. It is essential when various strengths of the product are available in the market.

For example, It will be wrong decision on the part of pharmacist to dispense the paracetamol tablet 500mg when the paracetamol tablet has not given any strength in the prescription.

4.  Dosage form of the drug prescribed :-

Many dosage form are available in the market in various dosage form, eg tablet, capsule, syrup, linctus etc.

The pharmaceutical dosage of the product should be written in the prescription in order to avoid ambiguity.

5.  Dose :-

 Usually high and low doses must be discussed with prescriber. Paediatric dose must be creating any kind of problem.

So the pharmacist should consider the paediatric posology in any case to avoid any misunderstanding. 

Sometimes a reasonable dose is administered too frequently, eg - a prescription for sustained release formulation to be administered after very few hours should be thoroughly checked because such dose forms are usually administered two or three times a day.

6.  Instructions for the patient :-

The instructions for the patient which are given in the prescription are incomplete or omitted.

The quantity of the drug to be taken, the frequency the mode of administration should be clearly given in the prescription so as to avoid any kind of confusion.

7.  Incompatibilities:-

It is essential to check that there are no pharmaceutical and therapeutic incompatibilities in the prescribed medication and the different medications to be prescribed to the same patient do not interact with other to produce any harm.

Certain antibiotics should not be given with meals since it significantly decreases the absorption of the drug.

 

Now let’s move to the technical chitchat. In the ancient period, the drugs were used to be dispensed in pure extemporaneous form. There were lots of incompatibility regarding that drug or medication. In simple words what is meant by incompatibility is the occurrence of undesired product whether due to known and unknown resources.

“Incompatibility may be defined as mixing two or more antagonistic substances resulting in an undesirable product, which may affect the safety, efficacy and appearance of the preparation.”

So there are three types of incompatibilities like –

1.     PHYSICAL INCOMPATABILITY.

2.     CHEMICAL INCOMPATAIBILITY.

3.     THERAPUETIC INCOMPATIBILITY.

 

1.  PHYSICAL INCOMPATIBILITY: -

When two or more antagonistic substances are combined together, a physical change takes place and the undesirable product is formed due to immiscibility, insolubility and liquefaction.

The changes are visible and can be corrected by the application of appropriate pharmaceutical skills to obtain the product of uniform dosage and attractive appearance.

1).   Immiscibility

Example:

Rx

 Castor oil :                                     15 ml

Water (q.s.) :                                 100 ml

 Incompatibility: Oil and water do not mix.

 Remedy: Carry out emulsification by the addition of an emulsifying agent, by the use of primary emulsion formula.

          2).  Insolubility

Example:

Rx

 Phenacetin:              3.33 g

Caffeine :                     1.11 g

Orange syrup :         13.3 ml

Water (q.s.)  :          100 ml

 Incompatibility: Phenacetin is an in diffusible solid.

 Remedy: Compound powder of tragacanth (2 g/100 ml of finished product) or tragacanth mucilage is used as a suspending agent.

 It increases the viscosity of the preparation and helps to maintain a uniform distribution of the insoluble substances for sufficiently long time after shaking the bottle in order to facilitate removal of a uniform dose.

          3).  Liquefaction :-

 

Example:

Rx

 Menthol :                           130 mg

Camphor:                            260 mg

Light magnesium oxide:   390 mg

 Incompatibility: When two organic substances having a low melting point are brought into physical contact with each other, they liquefy due to the formation of a new substance that has a melting point below room temperature.

The reason for this change is that each ingredient acts as an impurity for the other, thereby lowering their melting point. Such substances are called eutectic substances.

Example: Menthol, camphor, thymol and ammonium chloride

 Remedy: Eutectic powders may be dispensed in following two ways:

(a)   They can be dispensed as a separate set of powders with directions that one set of each powder may be taken as a single dose.

(b)   They can also be dispensed by adding a high melting point inert substance such as kaolin, starch, lactose or light magnesium oxide.

These substances act as adsorbents and prevent liquefaction.

ALKALOIDAL SALTS 

2.  CHEMICAL INCOMPATIBILITY :-

This are caused by complex formation, pH changes, oxidation- reduction, hydrolysis and combination reaction.

Such incompatibility can be noticed by effervescence ,explosion, colour change, precipitation, decomposition.

Chemical incompatibility is of two types-

a). Tolerated :

In tolerated incompatibilities, the chemical interaction can be decreased by changing the order of mixing or mixing in the dilute form but no alteration is made in the formulation.

b). Adjusted :

In tolerated incompatibilities, the chemical interaction can be minimized by addition or substitution of one of the ingredients of a prescription with equal therapeutic qualities.

 For eg caffeine citrate can be substituted with caffeine with sodium salicylate and caffeine citrate mixture.

The chemical incompatibility can be of two types – i) intentional and ii) unintentional.

 

A] Alkaloidal incompatibility :-

 1).  Alkaloidal salts with alkaline substances:

Alkaloids are weak bases which are slightly soluble or insoluble in water but alkaloidal salts are soluble in water.

 If these salts are dispensed with alkaline preparations such as strong ammonia solution or ammonium bicarbonate, the free alkaloid may be precipitated out.

Example :

Rx

Strychnine hydrochloride solution     6ml

Aromatic spirit of ammonia                  4ml

Water upto                                              120ml

 

 Incompatibility: Strychnine hydrochloride is an alkaloidal salt, whereas aromatic spirit of ammonia is an alkaline substance.

 When they both react, strychnine gets precipitated because the quantity of strychnine hydrochloride prescribed is more than its solubility in water. This preparation contains negligible amount of alcohol that cannot dissolve strychnine.

Hence, it gets precipitated as diffusible precipitate.

 Remedy: Divide the vehicle into two portions. The reactants are dissolved in separate portions and mixed slowly by adding one to the other with rapid stirring.

2) Alkaloidal salts with soluble iodides :-

In cough mixture, potassium iodide is generally prescribed along with tincture ipecacuanha.

The quantity of emetine present in the solution is usually very low to get precipitate as iodide.

Similarly when strychnine is prescribed with soluble iodides it forms a very insoluble hydroiodide, a precipitate.

3) Alkaloidal salts with tannins:

The alkaloidal salts when comes in contact with tannins, the alkaloidal forms tannates which are separate as diffusible precipitates.

The tannates are insoluble in water, hence strong tea or tannic acid solution are commonly used in alkaloidal poisoning.

4) Alkaloidal salts with salicylates:

When quinine salts are combined with salicylates, they form diffusible form of salicylates. Therefore follow the method B for precipitate yielding interaction.

Example :

Rx

Quinine hydrochloride           0.12g

Sodium salicylate                     4g

Water upto                                100ml

Make a mixture

Quinine hydrochloride on reaction with sodium salicylate which get separate as precipitates.

 Therefore follow the method B for precipitate yielding interaction.

5) Alkaloidal salts with soluble iodide and bromides:

Alkaloidal salts with strychnine form insoluble hydroiodide and hydrobromide forms soluble iodide and bromide.

These precipitates are insoluble but diffusible, hence follow method A for the precipitate yielding interaction.

example :

Rx

Potassium iodide                           1.5g

Tincture of stramonium               8.5ml

Chloroform water to make          100ml

Tincture stramonium contains solanaceous alkaloid, which form diffusible precipitates of hydroiodide with potassium iodide.

So follow method A for dispensing in prescription.

 

B] SOLUBLE SALICYLATES INCOMPATIBILITIES :

1) Soluble salicylates with ferric salt :

Ferric salt react with sodium salicylates to liberate diffusible precipitates of ferric salicylate.

Therefore, follow method B for the dispensing the prescription.

2) Soluble salicylates with alkali bicarbonates: Example:

Rx   

Sodium salicylate                 10 g

 Sodium bicarbonate  4g

 Chloroform water (q.s.)    100 ml

 Incompatibility: If sodium salicylate solutions are dispensed with alkaline substances such

as sodium bicarbonate, the mixture undergoes oxidation (by absorbing oxygen) and turns reddish brown. This does not change the therapeutic efficacy of the mixture, but may lead to anxiety in the patient. Remedy: A dark coloring agent like liquorice liquid extract may be added.

OR

An antioxidant such as sodium metabisulfite (0.1% w/v) can be added to prevent oxidation.

 5).  Soluble salicylates and benzoates with acids :

Most acids and acid syrups decompose sodium salicylate or sodium benzoates to form precipitates of salicylic acid and benzoic acid, respectively.

Example:

Rx

Sodium salicylate                 5.01 g

 Lemon syrup                25 ml

 Water (q.s.)         100 ml

 Incompatibility: Lemon syrup contains citric acid. When it reacts with sodium salicylate, in diffusible precipitates of salicylic acid are formed.

 Remedy: Divide the vehicle into two portions. The first reactant is dissolved in the first portion.

 Suitable amount of compound tragacanth powder is weighed (2 g/100 ml of the finished product) into a mortar and triturated with the second portion of the vehicle to form smooth mucilage.

The second reactant is dissolved in this mucilage and adjusted to suitable volume. The first mixture is then slowly added to the second mixture with rapid stirring.

OR

 Replace lemon syrup with a mixture of plain syrup and tincture of lemon.

 6. Incompatibility leading to evolution of CO2 :-

When carbonates or bicarbonates and acidic drugs are dispensed in a mixture along with water, they react together leading to the evolution of CO2.

Remedy: To prevent container leakage or explosion, the reaction must be completed before the preparation is transferred to the container. The ingredients are mixed in an open vessel and the effervescence reaction is allowed to complete after which it is transferred.

 Example:

Rx

 Sodium bicarbonate                  4 g

 Borax                                            2 g

 Glycerol                                       20 ml

 Water (q.s.)                                 100 ml

Incompatibility: When borax and glycerol are mixed together, hydrolysis of borax takes place with the formation of boric acid.

Remedy: All the ingredients are mixed effervescence is allowed to take place and if needed slightly warmed. Once it stops, it is transferred to the container.

7). Herapathite reaction (quinine sulphate with iodides) :-

Example:

Rx   

 Quinine sulphate                    5 g

 Dilute sulphuric acid               10 ml

 Potassium iodide                    1.5 g

 Water (q.s.)                             100 ml

 Incompatibility: Quinine sulphate is not freely soluble in water. It is made soluble in the presence of dilute sulphuric acid. The sulfuric acid liberates hydroiodic acid from the potassium iodide.

The hydroiodic acid is partly oxidized by sulphuric acid, yielding iodine.

The iodine, hydroiodic acid and quinine sulphate then combine to form a compound called “herapathite or iodosulfate of quinine”. The mixture formed is quite clear at first but after about three days, it may deposit bronze or olive green scales, which are due to “herapathite reaction for quinine”.

 Remedy: To avoid any problems, it should be given to the patient only for about three days.

Or

 The mixture should be divided, sending the potassium iodide in one bottle and quinine sulphate in another bottle. The patient should be advised to mix the solutions and take the necessary dose.

8. Soluble iodides with potassium chlorate :-

Example:       

Rx

 Potassium chlorate                       2.22 g

Syrup of ferric iodide                      27.8 ml

Water (q.s.)                                      100 ml      

 Incompatibility: The ferric iodide is oxidized by potassium chlorate and the reaction is as follows:

KClO3 + 3FeI3 → 3FeOI + 3I2 + KCl

 Remedy: The mixture is clear when freshly prepared but deposits crystals of iodine upon storage

for sometime. So, the two reacting substances must be dispensed in separate bottles with a label

indicating “Mix the contents of both the bottles before use”

9. Potassium chlorate and oxidizable substances (Explosive mixture):

 Example:

Rx

Potassium chlorate            0.6 g

Tannic acid                           0.3 g

Sucrose                                 0.3 g

Incompatibility: When potassium chlorate (oxidizing agent) is triturated or heated with readily oxidizable substances (reducing agents) such as charcoal, sulphur or tannic acid, there are chances of an explosion.

 Remedy: Potassium chlorate and tannic acid are triturated individually. Then the powders are mixed separately with half the quantities of powdered sucrose and finally they are mixed together lightly using a spatula.

The therapeutic incompatibility will be continued in next blog......

till then signing off Sarang More, take care.