27087888 Physical and Chemical Incompatibilities

7/25/2019 27087888 Physical and Chemical Incompatibilities

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1

ARMACEUTICAL INCOM ATIBILITY

PHYSICAL

AND

CHEMICAL INCOMPATIBILITY

BY

K.SAMINATHAN. M.pharm, M.B.A,( P.hD)Allianze college of meical !cience!


2/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia"

pharmaceutical incompatibility occurs as a

result of mixing of two or more antagonisticsubstances 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.


3/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia#

TYPE OF !"O#P$T%&TE'(

A) Physical incompatibilityB) Chemical incompatibility

C) Therapeutic incompatibility


4/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia$

$)P*Y'"$& !"O#P$T%&TY(

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 isible and can be easily corrected by

applying the pharmaceutical skill obtain a product ofuniform dosage, substance to help in compounding

of the prescription.


5/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia%

An attractie incompatibilities may be corrected by using any one or

more of the following method.

Change the order or mi!ing of the prescription

"mulsification

Adding of suspending agent

Change in the form of ingredients

By adding, substitution or omission of therapeutically inactie

&'ample! of ph!ical incompai*iliie!

vIMMIS+IBIIT-

vINS/BIIT-

vP0&+IPITATIN

vI/&2A+TIN


6/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia3

##'"%&TY

#ils and water immiscible with each other.They can be made miscible with water byemulsification."!ample$

Castor oil %&mlWater '(mlake on emulsion.

*n this prescription castor oil is immiscible with

water.To oercome this incompatibility anemulsifying agent is used to make a good emulsion


7/23


!'O&+%&TY

*nsolubility means the inability of material to dissole in a

particular system. The ma+or of incompatibilities are due to insolubility of

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

"!ample$ %

"phedrine sulphate (.&gmenthol (.(ml

-iuid paraffin /sufficient to make) 0(ml

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

liuid paraffin, but anhydrous ephedrine is soluble in it. 1ence ephedrine

sulphate is substituted with anhydrous ephedrine to make a clear

solution.


8/23


"!ample$

Phenacetin 0g

Caffeine %g

#range syrup % ml

Water up to 2(ml

*n this prescription Phenacetin is an

indiffusible substance. Compound powder of

tragacanth or mucilage of tragacanth is used as asuspending agent to make a suitable suspension


9/23


PE"PT$TO!A drug in solution may be precipitated, if the solent

in which it is insoluble is added to the solution."!ample$

The resins are insoluble in water. When thetincture containing resins is added in water, resin

agglomerates forming indiffusible precipitates.

This can be preented by slowly adding theundiluted tincture with igorous stirring to the diluted

suspension#rBy adding some suitable thickening agent


10/23


&-+EF$"TO!

When certain low melting point solids are mi!ed together,

a liuid or soft mass known as eutectic mi!tureis produced.

This occurs due to the lowering of the melting point of mi!ture to

below room temperature and liberation of water of hydration.

any chemicals form hydrates, compounds with water of

hydration.

The medicaments showing this type of behaior are

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

This type of substance create problem when they are dispensed

in powder form.


11/23


"!ample$

enthol &gCamphor &g

Ammonium chloride 0(g-ight magnesium carbonate '(g

*n this prescription menthol, camphor andammonia chloride get liuefied on mi!ing with eachother. To dispense this prescription, mentholcamphor and ammonium chloride are triturated

together to form liuid. Add light magnesiumcarbonate and mi! it thoroughly to make freeflowing powder.


12/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia1"

"*E#"$& !"O#P$T%&TY

Chemical incompatibility may be as a result of

chemical interactions between the ingredients of a

prescription and a to!ic or inactie product may be formed.

Chemical incompatibilities often occur due to

o!idation 3reduction. Acid base hydrolysis or combination

reaction. These reactions may be noticed by precipitation

efferescences, decomposition, colour change or by

e!plosion.


13/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia1#

"*E#"$& !"O#P$T%&TY ' TO TYPE'(

%) Tolerated$

*n tolerated incompatibilities. The chemical interaction can be

minimi4ed by changing the order of mi!ing or mi!ing the solutions in

dilute forms but no alteration is made in the formulation.

) Ad+usted$*n ad+usted incompatibilities the chemical interaction can be

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

a prescription with another of eual therapeutic alue.

"!ample$

Caffeine citrate can be substituted with caffeine in sodiumsalicylate and caffeine citrate mi!ture.


14/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia1$

"*E#"$& !"O#P$T%&TY #$Y %E(

*5T"5T*#5A-$

When the prescriber knowingly prescribes the

incompatibility drugs.

65*5T"5T*#5A-$

When the prescriber prescribes the drugs

without knowing that there is incompatibility

between the prescribed drugs.


15/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia1%

PE"PT$TE YE&/!0 !TE$"TO!'

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 respectiely.

#ET*O/ 1$)(

The method is followed when diffusible precipitates are

formed in ery small uantity. 7iide the ehicle into two eual

portions. 7issole one of the reacting substances in one of the

portion and the other in the other portion. i! the two portions by

slowly adding one portion to the other by rapid stirring.


16/23


#ET*O/ 1%)

The method is followed when indiffusible precipitates are formed

in large uantity. 7iide the ehicle into two portions. 7issole one of the

reacting substances in one portion. Weigh a suitable uantity of

compound tragacanth powder /g per %(( ml of finished product) and

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

smooth mucilage. Then add other reacting substances. i! the two

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

A secondary label shake the bottle before useshould be fi!ed

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

dispensing the prescription.


17/23


2.$lkaloidal salts with alkaline substances(

Alkaloids are weak bases. They arealmost insoluble in water but alkaloidal salts

are soluble in water. *f these salts aredispensed with alkaline preparations, suchas, strong solution of ammonium acetate,

aromatic spirit of ammonia, solution ofammonia. Ammonium bicarbonate, the freealkaloid may be precipitated.


18/23


Example(

8trychnine hydrochloride solution ' ml

Aromatic spirit of ammonia 9 mlWater make up to %(( ml

8trychnine 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 uantity of strychnine

hydrochloride prescribed in the prescription is much more than its

solubility in water /% in :(((). The aromatic spirit of ammonia contains

negligible amount of alcohol which can nor dissoles the strychnine.

1ence it gets precipitated as diffusible precipitates. 1ence it gets

precipitated as diffusible precipitates. 1ence follow method $ for

precipitate yielding combination.


19/23


. 8#-6B-" 8A-*C;-AT"*5C#PAT*B*-*T*"8$8oluble salicylate with ferric salt$


20/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia"7

0. 8#-6B-" *#7*7"8 *5C#PAT*B*-*T*"8$*odides undergo o!idation forming iodine

which is an undesirable product. 1ence, followingsteps may be taken to aoid this chemical change."!ample$

#!idation of iodides with potassium chlorate$When soluble iodides react with potassiumchloride, free iodine is liberated.

=C*#0 > 0=C*

To preent the incompatibility, the tworeacting substances must be dispensedseparately.


21/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia"1

9. "*E#"$& !"O#P$T%&TY "$+'!0 E3$&+TO!

OF "$%O!/O4/E 0$'.

Bismuth sub nitrate when combined with sodium

bicarbonate when combined with sodium bicarbonate in thepresence of water, carbon dio!ide gas is liberated due to the

following reaction.

Bi#5#0 >5a1C#0 /Bi#) C#0 > 5a5#0>C# >1#


22/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia""

5.!"O#P$T%&TY OF E#+&'FY!0 $0E!T'(

"mulsion prepared with alkali metal, ammonia and

triethanoamine soaps are incompatible with salts producing

polyalent cations. 7ue to double decomposition, a

polyalent soap is formed which inerts the emulsion.

6."O&O+ 'T$%&TY OF /YE'(

The colour of the most of the dyes used in

pharmaceutical formulation is influenced by their ioni4ation

which depends on P* of the solution.

The phenolphthalein dye is colorless in acid solution but

red in alkaline mi!ture.

THANK


23/23

K.SAMINATHAN. M.pharm, M.B.A,( P.hD) Allia"#

THANK

YOU

27087888 Physical and Chemical Incompatibilities

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