This document discusses preformulation and the various degradative pathways that can occur with drugs, including hydrolysis, oxidation, racemization, polymerization, and others. It provides examples of each type of degradation, factors that influence them, kinetics, and general methods for preventing degradation, such as controlling temperature, light exposure, pH, and proper packaging. Preformulation involves investigating a drug's physical and chemical properties alone and with excipients to guide rational dosage form development and ensure stability.

1. PREFORMULATION
TOPIC : Degradative pathways of drugs
(chemical properties)
Presented by
K JEBASTIN.B.Sc.,M.Pharm.,
Dept of Pharmaceutics
Madurai Medical College

2. PREFORMULATION
 “pre-formulation” literally refers to the
steps to be undertaken before formulation
proper.
 It can be defined as an investigation of
physical and chemical property of a drug
substance alone and when combined with
excipients.
 Preformulation testing is the first step in
the rational development of dosage forms.

3. CHEMICAL DEGRADATION
1. Hydrolysis
2. oxidation & reduction
3. racemisation
4. polymerization
5. Photolysis
6. Isomerization
7. Decarboxylation
8. Enzyme decomposition

4. • Hydrolysis means “splitting by water”
• Hydrolysis is the chemical reaction with H2O molecule
• Generally it follows second order kinetics
Hydrolysis mainly occurs in, which compounds having ester
and amide functional group.
Examples for hydrolysable compounds
HYDROLYSIS
s.no drugs example
1 Esters Aspirin, alkaloids
2 Lactones Pilocarpine, spirinolactone
2 Amides Chloramphenicol
4 Lactams Penicillin, cephalosporin
5 imides glutethimides

5. 1. rupture of covalent linkage between carbon
atom and oxygen atom
The hydrolysis of ester into mixture of acid
&alcohol
ex : aspirin
This follows pseudo-first order kinetics
2.A hydrolytic reaction can proceed as a result of
ring cleavage with subsequent attack by hydrogen
or hydroxyl ion
Example : hydrochlorthiazide, pilocarpine
HYDROLYSIS

6. PREVENTION FROM HYDROLYSIS
❖ Adjusting the pH
❖Addition of water miscible solvents
❖Addition of optimum buffer
❖Addition of surfactants
❖Complexation with chelating agent ex : EDTA
❖Structure modification
❖Alteraton of dielectric constant
❖Stored with desscicant

7. OXIDATION
Oxidation is defined as removal of electropositive
atoms or addition of electro negative atom
This reaction is mediated either by free radicals or
molecular oxygen
Types
1. Auto oxidation
2. Free radical chain process
a) initiation
b) propagation
c) decomposition
d) termination

8. FACTORS INFLUENCING OXIDATION
1. The amount of light
2. Temperature
3. Concentration of oxygen
4. Presence of heavy metals
5. Hydrogen – hydroxyl ion

9. STEPS TO PREVENT THE OXIDATION
1. Addition of boiling water to reduce the oxygen content
2. To avoid light exposure ( stored in cool & dark place)
3. Addition of anti oxidant ( reducing agent)
a) oil soluble anti oxidant e.g BHA, BHT, α – tocopherol
b) water soluble anti oxidant e.g sod.meta bi sulphite,
sod.sulphite, ascarbic acid
4. Addition of chelatin agent e.g EDTA, citric acid, tartaric acid
5. Changing the pH
6.Changing the solvent

10. RACEMIZATION
 It is the process of inter conversion from one isomer to
another isomer, which is having different pharmacokinetics
as well as different pharmacological and toxicological effect
 It can defined in other words “optically active drugs is
converted it’s enantiomer ”
 Racemization follows first order kinetics
Examples:
1. Levo form of epinephrine 15-20 times more active
than dextro form
2. Levo form of cetrizine is more active than dextro form

11. FACTORS INFLUENCING
THE RACEMIZATION
1. temperature
2. solvent
3. catalyst
4. presence or absence of light

12. POLYMERIZATION
It is the process of formation of complex molecules
by continues reaction of two or more identical
molecules.
Here more than more than one monomer reacts
together to produce polymer
Examples
❖ Darkening of glucose solution

13. GENERAL METHODS TO PREVENT
THESE DEGRADATION
1.All the products should be stored in suitable temperature
to avoid thermal decomposition
2. Light sensitive material should be stored in ambered
colour bottles
3. Choosing packaging material like glass , plastic to
prevent exposure of drug to high humid condition
4. Proper packaging leads prevention from oxidation
5. Addition of suitable solvent system may reduce the
hydrolysis