Antioxidants are used to prevent oxidation of drugs and excipients in formulations. They work by either sacrificing themselves through redox reactions or inhibiting the chemical chain reaction of oxidation. There are three main types of antioxidants - water soluble antioxidants that act as reducing agents, lipid soluble antioxidants that directly prevent oxidation, and antioxidant synergists called chelating agents that increase the effectiveness of other antioxidants by binding to heavy metals.

1. ANTIOXIDANTS
OXIDATION- It is defined as a loss of electron from a compound that results
in a change in the oxidation state of the molecule. this reaction is mediated
by O2 or free radicles, and reaction is catalyzed by heavy metals.
DRUG + O2 / free radicles DRUG+ + e-
Heavy metal(Pt/Pd)
light

2. MECHANISM OF OXIDATION
STEP 1- INITIATION (GENERATION OF FREE RADICLES): Free radicles are deficient of electrons.
O2 O + O
STEP 2- PROPAGATION (CHAIN ELONGATION): Actual oxidation begins.
Rate determining step and critical step of oxidation.
DRUG + O DRUG+ + e-
STEP 3- TERMINATION (CHAIN TERMINATION):
O + O O2
Light . .
.
. .

3. ROLE OF HEAVY METALS IN OXIDATION!!
HEAVY METAL
GO FREE RADICLE!!
GO, AND ATTACK THE DRUG SUBSTANCE
HEAVY METAL
Pt/Pd

4. WHAT IS ANTIOXIDANTS??
Antioxidants are used to prevent the oxidation of active substance or
excipients present in formulation.
HOW THEY DO THAT?? (MECHANISM OF ANTIOXIDANTS)
# THEY DO IT BY 2 WAYS:
• By sacrificing and developing REDOX SYSTEM.
• By acting as a CHAIN INHIBITORS

5. MECHANISM OF ANTIOXIDANT
By sacrificing and developing REDOX SYSTEM:
By acting as a CHAIN INHIBITORS:
Drug substance
Antioxidant
Free radicle
Breaking chemical chain
Redox system
Antioxidant
giving electron
or H+ ion.
Free radicle
Inhibiting chain
propagation.

6. TYPES OF ANTIOXIDANTS
There are mainly three types of Antioxidants-
• Water soluble Antioxidants (REDUCING AGENTS)
• Lipid soluble Antioxidants (TRUE ANTIOXIDANTS)
• Antioxidant synergists (Chelating agents).
Butylated hydroxy toluene
(BHT)
Ascorbic acid
EDTA

7. WATER SOLUBLE ANTIOXIDANTS
ALSO CALLED AS REDUCING AGENTS
THEY ACT AS SACRIFICER.
Free radicle
Drug
substance
Protecting the drug substance from free
radicle, by sacrificing himself.
Antioxidant having
high oxidation state
MECHANISM INVOLVED
Getting oxidized and acting
as reducing agent.
Ascorbic acid

8. Drug substance
Free radicle
acceptor
Antioxidant
Free
radicles
No propagation, therefore
the oxidation is inhibited.
LIPID SOLUBLE ANTIOXIDANT
MECHANISM INVOLVED
Butylated hydroxy toluene (BHT)

9. CHELATING AGENTS
Effectiveness of Antioxidants depends on-
• Concentration of antioxidant used
• Nonreactivity
• Solution Ph
• Package integrity
Chelating agents are also called antagonist synergists. They increase the
effectiveness of antioxidants, by forming complex with heavy metals.
EDTA

10. WATER SOLUBLE ANTIOXIDANTS
SODIUM SULFITE SODIUM BISULFITE SULFUR DIOXIDE
ASCORBIC ACID THIOGLYCOLIC ACID ACETYLCYSTEINE

11. LIPID SOLUBLE ANTIOXIDANTS
HYDROQUINONE PROPYL GALLATE BUTYLATED HYDROXY TOLUENE
α- TOCOPHEROL LECITHIN BUTYLATED HYDROXY ANISOLE

12. CHELATING AGENTS
EDTA CITRIC ACID
TARTARIC ACID DIHYDROXYETHYL GLYCINE