Physical and Chemical Incompatibilities

1

PHARMACEUTICAL INCOMPATIBILITY

PHYSICAL AND

CHEMICAL INCOMPATIBILITYBY

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allianze college of medical sciences


2

pharmaceutical incompatibility occurs as a

result of mixing of two or more antagonistic

substances and an undesirable product is formed

which may affect the safety, efficacy and

appearance of pharmaceutical preparation.

Pharmaceutical incompatibility may occur not

only during compounding and dispensing but also

at any stage during compounding and dispensing

but also at any stage during formulation,

manufacturing, packing or administration of drugs.


3

TYPE OF INCOMPATIBILITIES:

A) Physical incompatibility

B) Chemical incompatibility

C) Therapeutic incompatibility


4

A) PHYSICAL INCOMPATIBILITY:

When two or more than two substances are

combined together, physical changes take place and

an unacceptable product is formed. These changes

which occurs as a result of physical incompatibility

are usually visible and can be easily corrected by

applying the pharmaceutical skill obtain a product of

uniform dosage, substance to help in compounding

of the prescription.


5

An attractive incompatibilities’ may be corrected by using any one or

more of the following method.

•Change the order or mixing of the prescription

•Emulsification

•Adding of suspending agent

•Change in the form of ingredients

By adding, substitution or omission of therapeutically inactive

Examples of physical incompatibilities

IMMISCIBILITY

INSOLUBILITY

PRECIPITATION

LIQUEFACTION


6

IMMISCIBILITY

Oils and water immiscible with each other. They can be made miscible with water by emulsification.Example:Castor oil 15mlWater 60mlMake on emulsion.

In this prescription castor oil is immiscible with water .

To overcome this incompatibility an emulsifying agent is used to make a good emulsion


7

INSOLUBILITYInsolubility means the inability of material to dissolve in a

particular system. The major of incompatibilities are due to insolubility of

the inorganic as well as organic compounds in a particular solvent.

Example: 1

Ephedrine sulphate 0.25gm

Menthol 0.02ml

Liquid paraffin (sufficient to make) 30ml

The ephedrine sulphate is an alkaloidal salt and is not soluble in

liquid paraffin, but anhydrous ephedrine is soluble in it. Hence ephedrine

sulphate is substituted with anhydrous ephedrine to make a clear

solution.


8

Example: 2

Phenacetin 3g

Caffeine 1g

Orange syrup 12 ml

Water up to 90ml

In this prescription Phenacetin is an

indiffusible substance. Compound powder of

tragacanth or mucilage of tragacanth is used as a

suspending agent to make a suitable suspension


9

PRECIPITATION A drug in solution may be precipitated, if the solvent in which it is insoluble is added to the solution.Example:

The resins are insoluble in water. When the tincture containing resins is added in water, resin agglomerates forming indiffusible precipitates.

This can be prevented by slowly adding the undiluted tincture with vigorous stirring to the diluted suspension OrBy adding some suitable thickening agent


10

LIQUEFACTION

When certain low melting point solids are mixed together,

a liquid or soft mass known as “eutectic mixture” is produced.

This occurs due to the lowering of the melting point of mixture to

below room temperature and liberation of water of hydration.

Many chemicals form hydrates, compounds with water of

hydration.

The medicaments showing this type of behavior are

camphor, menthol, thymol, phenol, chloral hydrate and aspirin.

This type of substance create problem when they are dispensed

in powder form.


11

Example:

Menthol 5gCamphor 5gAmmonium chloride 30g

Light magnesium carbonate 60g

In this prescription menthol, camphor and ammonia chloride get liquefied on mixing with each other. To dispense this prescription, menthol camphor and ammonium chloride are triturated together to form liquid. Add light magnesium carbonate and mix it thoroughly to make free flowing powder.


12

CHEMICAL INCOMPATIBILITY

Chemical incompatibility may be as a result of

chemical interactions between the ingredients of a

prescription and a toxic or inactive product may be formed.

Chemical incompatibilities often occur due to

oxidation –reduction. Acid base hydrolysis or combination

reaction. These reactions may be noticed by precipitation

effervescences, decomposition, colour change or by

explosion.


13

CHEMICAL INCOMPATIBILITY IS TWO TYPES:

1) Tolerated:

In tolerated incompatibilities. The chemical interaction can be

minimized by changing the order of mixing or mixing the solutions in

dilute forms but no alteration is made in the formulation.

2) Adjusted:

In adjusted incompatibilities the chemical interaction can be

prevented by addition or substitution of one of the reacting ingredients of

a prescription with another of equal therapeutic value.

Example:

Caffeine citrate can be substituted with caffeine in sodium salicylate and caffeine citrate mixture.


14

CHEMICAL INCOMPATIBILITY MAY BE:

INTENTIONAL:

When the prescriber knowingly prescribes the

incompatibility drugs.

UNINTENTIONAL:

When the prescriber prescribes the drugs

without knowing that there is incompatibility

between the prescribed drugs.


15

PRECIPITATE YIELDING INTERACTIONS

The precipitate form through the chemical incompatibility

may be diffusible or indiffusible. The method A and B is followed

in dispensing the prescription yielding diffusible and indiffusible

precipitates respectively.

METHOD (A):

The method is followed when diffusible precipitates are

formed in very small quantity. Divide the vehicle into two equal

portions. Dissolve one of the reacting substances in one of the

portion and the other in the other portion. Mix the two portions by

slowly adding one portion to the other by rapid stirring.


16

METHOD (B)

The method is followed when indiffusible precipitates are formed

in large quantity. Divide the vehicle into two portions. Dissolve one of the

reacting substances in one portion. Weigh a suitable quantity of

compound tragacanth powder (2g per 100 ml of finished product) and

transfer in a mortar and use part of second portion of vehicle to produce

smooth mucilage. Then add other reacting substances. Mix the two

portions by slowly adding one portion to the other with rapid stirring.

A secondary label “shake the bottle before use” should be fixed

on the container whenever method A or method B is followed in

dispensing the prescription.


17

1. Alkaloidal salts with alkaline substances:

Alkaloids are weak bases. They are almost insoluble in water but alkaloidal salts are soluble in water. If these salts are dispensed with alkaline preparations, such as, strong solution of ammonium acetate, aromatic spirit of ammonia, solution of ammonia. Ammonium bicarbonate, the free alkaloid may be precipitated.


18

Example:

Strychnine hydrochloride solution 6 ml

Aromatic spirit of ammonia 4 ml

Water make up to 1200 ml

Strychnine hydrochloride is an alkaloidal salt were as aromatic

spirit of ammonia is an alkaline substance. When they react together,

the strychnine get precipitated because the quantity of strychnine

hydrochloride prescribed in the prescription is much more than its

solubility in water (1 in 7000). The aromatic spirit of ammonia contains

negligible amount of alcohol which can nor dissolves the strychnine.

Hence it gets precipitated as diffusible precipitates. Hence it gets

precipitated as diffusible precipitates. Hence follow method A for

precipitate yielding combination.


19

2. SOLUBLE SALICYLATE INCOMPATIBILITIES:Soluble salicylate with ferric salt:

Ferric salt reacts with sodium salicylate to liberate indiffusible precipitates of ferric salicylate therefore follow method B for precipitate yielding interactions.Example:

Ferric chloride solution 2mlSodium salicylate 3 gWater make up to 90 ml


20

3. SOLUBLE IODIDES INCOMPATIBILITIES:Iodides undergo oxidation forming iodine

which is an undesirable product. Hence, following steps may be taken to avoid this chemical change.Example:

Oxidation of iodides with potassium chlorate:When soluble iodides react with potassium chloride, free iodine is liberated.

KCIO3 + 3FeI2 3FeOI +3I+KCI

To prevent the incompatibility, the two reacting substances must be dispensed separately.


21

4. CHEMICAL INCOMPATIBILITY CAUSING EVALUTION

OF CARBONDIOXIDE GAS.

Bismuth sub nitrate when combined with sodium

bicarbonate when combined with sodium bicarbonate in the

presence of water, carbon dioxide gas is liberated due to the

following reaction.

2BiONO3 +2NaHCO3 (BiO) 2 CO3 + 2NaNO3 +CO2 +H2O


22

5.INCOMPATIBILITY OF EMULSIFYING AGENTS:

Emulsion prepared with alkali metal, ammonia and

triethanoamine soaps are incompatible with salts producing

polyvalent cations. Due to double decomposition, a

polyvalent soap is formed which inverts the emulsion.

6.COLOUR STABILITY OF DYES:

The colour of the most of the dyes used in

pharmaceutical formulation is influenced by their ionization

which depends on PH of the solution.

The phenolphthalein dye is colorless in acid solution but

red in alkaline mixture.


23

THANK YOU

Physical and Chemical Incompatibilities

Documents

Transcript of Physical and Chemical Incompatibilities