Routes of drug degradation

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Presented by:
Aditya Singh
PhD (Pharmaceutics)
2001014
Applied Pharmaceutics

2.  Introduction
 Conditions mostly used for forced degradation
studies
 Hydrolytic conditions
 Oxidation conditions
 Photolytic conditions
 Thermal conditions
 Humidity
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3.  Drug degradation is also known as forced degradation.
 The ICH guideline states that stress testing is intended to
identify the likely degradation products which further helps
in determination of the intrinsic stability of the molecule and
establishing degradation pathways, and to validate the
stability indicating procedures.
 The stability of the API through the establishment of various
tests and the way there are conducted (ICH Q1A, 1993). The
confirmation of the presence of impurities is performed (ICH
Q3A, 1993).
 Stress testing includes strong acid, base, hydrogen peroxide,
high temperature or light, in (ICH Q1A (R2).
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4.  Degradation studies area regulatory requirement and
scientific necessity during drug development, it is not
considered as a requirement for formal stability program.
 The International committees for Harmonization of Technical
Requirements for Registration of pharmaceutical Human use
(ICH) has published a set of guidelines i.e. ICH Q1A
Stability Testing of New Drug Substances and Products ICH
Q1B Photo stability Testing of New Drug Substances and
Products ICH Q2B Validation of Analytical Procedures:
Methodology. In ICH Q1A section 2.1.2 consider routes of
drug degradation.
 Currently Swiss Target software are most widely used to
determine the drug degradation rate.
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6. Degradation Type Storage Condition
Hydrolysis 40°C
Oxidation 60°C
Photolytic NA
Thermal 60°C
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8.  Hydrolysis is one of the most common degradation chemical
reactions over a wide range of pH. Hydrolysis is a chemical
process that includes decomposition of a chemical compound
by reaction with water Hydrolytic study under acidic and
basic condition involves catalysis of ionizable functional
groups present in the molecule. Acid or base stress testing
involves forced degradation of a drug substance by exposure
to acidic or basic conditions which generates primary
degradants in desirable range. The selection of the type and
concentrations of acid or base depends on the stability of the
drug substance.
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9.  Hydrogen peroxide is widely used for oxidation of
drug substances in forced degradation studies but
other oxidizing agents such as metal ions, oxygen,
and radical initiators.
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10.  The photo stability testing of drug substances must
be evaluated to demonstrate that a light exposure
does not result in unacceptable change. Photo
stability studies are performed to generate primary
degradants of drug substance by exposure to UV or
fluorescent conditions.
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11.  Thermal degradation (e.g., dry heat and wet heat) should be
carried out at more strenuous conditions than recommended
ICH Q1A accelerated testing conditions.
 Samples of solid-state drug sub- stances and drug products
should be exposed to dry and wet heat, while liquid drug
products should be exposed to dry heat.
 Studies may be conducted at higher temperatures for a
shorter period Effect of temperature on thermal degradation
of a substance is studied through the Arrhenius equation:
 k = Ae-Ea/RT
 where k is specific reaction rate, A is frequency factor, Ea is
energy of activation, R is gas constant (1.987cal/degmole)
and T is absolute temperature . Thermal degradation study is
carried out at 40–80°C. 11

12.  Humidity is the Key factor in establishing the
potential degradants in the finished product and
active pharmaceutical ingredient. Normally 90%
Humidity for duration of one week shall be
recommended for the establishment of forced
degradation samples.
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13.  Drug is spoiled by 3 main routes physical, chemical,
microbiological.
 Pure drug are most stable than their formulation.
 Drug degradation breakdown of a drug is a chemical
reaction involving the collision of molecules.
 The most of drug degrade by hydrolysis, oxidation,
reduction, etc.
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 Carstensen, J. T., and Rhodes, C. H. (eds). (2000). Drug
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