3. 3
Group # 5
Roll # 41 to 50
Presented to :
Dr . MISBAH
presenter : EAMEN SAEED(D18E46)
4. .
The condition or
process of degrading
or being degraded.
Decline to a lower
quality, condition or
level. 4
5. The incapacity or
incapability of a
particular formulation in
a specific container to
remain with in a
particular chemical,
micro biological,
therapeutical, physical &
toxicological
specification.
5
6. There are three types;
1- Physical degradation
2- Chemical degradation
3- Microbiological degradation
6
7. “Separation of chemical
compound into elements
or simpler compounds.
Change in chemical
nature of drug is called
as chemical
degradation.’’
7
8. 8
• 1- H Y D R O L Y S I S
• (a) ionic hydrolysis
• (b) molecular hydrolysis
ester
amide
2- O X I D A T I O N
(a) auto oxidation
(b) photo oxidation
3- I S O M E R I Z A T I O N
(a) optical isomerization
(b) geometrical isomerization
4- DECARBOXYLLATION
5- POLYMERIZATION
6- DEHYDRATION
7- ABSORPTION OF CO2
8- PHOTO DEGRADATION
• There are following types of chemical
degradation:-
10. 10
“Breakdown of drug molecule in
presence of water or due to water”
TYPES:
(a) ionic Hydrolysis
(b) molecular hydrolysis
(a)Ionic Hydrolysis:
it occurs when a salt of a weak acid or weak base (or both) is dissolved in water.
the salt breaks down into positive and negative ions.
e.g :
• sodium acetate +water sodium ion +acetate ion
• ammonia + water ammonium ion +hydroxyl ion
11. 11
• (b) Molecular Hydrolysis:
“ It is much slower,irreversible process involving
cleavages of drug molecule.”
• Upon hydrolysis ,ester is converted into alcohol and carboxylic aid in
presence of acidic or alkaline medium.
• Degradation rate depends upon leaving group ability.
• Bulky groups on either R1 or R2 decrease decomposition rate.
• hydrolysis of Ester involves rupture of covalent bond between carbon &
oxygen.
Ester hydrolysis:
12. 12
• Cocain with two ester
bonds, upon hydrolysis
converted into
ecgonine methyl ester.
• Lactones (cyclic
esters pilocarpine),
Dalvastatin and
Warfarin undergoes
hydrolysis due to ring
opening.
13. 13
• These are usually found in drug molecule.
• They are more stable than Esters because carbonyl carbon of amide bond
is less electrophilic.
• The leaving group “an ammine” is poorer leaving group.
Amide hydrolysis:
17. 17
“Removal of an electropositive atom, redical .or electrone.”
OR
“addition of an electronegative atom or redical.”
TYPES:
o Auto-oxidation
o Photo-oxidation
Auto-oxidation:
it occurs in presence of oxygen or UV radiation and forms peroxides & hydro peroxides.
it proceeds slowly under influence of Oxygen.
e.g: oils , fats, unsaturated compounds can undergo auto oxidation.
18. 18
Photo-oxidation:
It occurs in absence of air.
Removal of electrone only in presence of light.
The susceptibility can be predicted from standard oxidation reduction potential given by following
relation :
Eh = Eס + 00592 log [oxidized form]
n [reduced form]
n = number of electrons transferred per ion.
Eο= oxidizing or reducing capacity.
compounds with higher Eο has low tendency to be oxidized.
e.g: it occurs in adrenaline, riboflavin, ascorbic acid.
21. 21
“It is the process by which one molecule is transformed
into another molecule which has exactly the same
atoms but with different arrangements.”
e.g: A-B-C B-A-C
“Conversion of an active drug into a less active or inactive
isomer having same structural formula but different
stereochemical configuration.
23. 23
• A change in optical activity of a drug may result as a change in its biological activity.
Racemization:
• it involves the optically active form of a drug into its enantiomers.
• e.g:
• By the action of heat ,(-) hyoscyamine is readily converted into atropine,which is
recimic mixture of (-) & (+) hyoscyamine.
Epimerization:
• it occur with the compound having more than one asymmetric carbon atom in the
molecule.
• e.g:
• under prolonged storage , solution containing Ergometrine is decomposed by
hydrolysis and isomerized to Ergometrinine.
24. 24
• Loss of activity due to the difference in potency exhibited by CIS
& TRANS isomers of some organic compound.
e.g:
Active form of Vitamin A molecule has all trans configuration.
In aqueous solution as a component of multi vitamin preparation , in
addition to oxidation Vitamin A PALMITATE isomerizes and forms
6-mono CIS and 2,6 - di CIS isomers, Both have low potency.
25. 25
“release of CO2 during a chemical reaction”
Drug substances having carboxylic acid group are sometimes
susceptible to decarboxylation.
The problem occurs when parenteral solution of
sodium Bicarbonate are autoclaved.
e.g :
para amino –benzoic acid Aniline +CO2
27. 27
“Combination of two or more than two identical
molecules to form a larger or complex molecule.”
The influence of microscopic dimensions ,heat treatment and polymer morphology
on the chemical degradation of poly (glycolic acid)PGA fibers and pellets was
examined in media of different pH values by monitoring the sample mass,
dimensions , crystallinity , mechanical strength and surface character.
Degradation is chemically controlled independent of fiber size .
The rate was an order of Magnitude …faster in alkaline vs. acidic media .
e . g:
degradation of antiseptic formulations and aldehyde is due to polymerization
formaldehyde solution may result into formation of white deposit when stand in
cold.
28. 28
“The conversion that involves the loss of water from the
reacting molecule or ion is known as DEHYDRATION.
e . g:
sugars such as GLUCOSE and LACTOSE form 5-Hydroxy methyl furfural.
erythromycin is susceptible to acid catalyzed reaction.
prostaglandin E1 and E2 undergo dehydration followed by isomerization .
30. 30
“ the absorption of CO2 from atmosphere by a
pharmaceutical product is more frequent than
loss of CO2 i.e. decarboxylation .”
Solution of KOH , NaOH , Ca(OH)2 become turbid due to formation of
insoluble carbonates on exposure to CO2.
31. 31
EFFECTS :
the most pronounced effect is seen on the stability solution of
sodium salts of barbiturates.
e.g:
solution of sodium hexobarbitone can absorb Co2 and these
result in the preparation of hexobarbitone/hexobarbital.
32. 32
“It is the process by which sensitive drugs or molecules
are chemically degraded by light ,room light or sunlight.”
o Before a photo degradation reaction can occur,
the energy from light radiation must be absorbed
by molecules.
o The variation of degradation depends
on the wavelength of light .
oShorter wavelength damages more
than longer wavelength.
33. 33
• Photo degradation of Primaquine & chloroquine give different
products by various pathways.
• Sodium Nitro prusside stable for 1 year if protected otherwise
degraded after 4 hours.
• PREVENTIONS:
• suitable packing in
amber colored bottles,
cardboard outers and
Aluminum foil over wraps.
34. “Be the OXYGEN
for all living
things…..
don’t get obsessed
to your superiors…”
