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PHARMACEUTICAL DEGRADATION
PRESENTED BY:
SAHARISH KHALIQ
DEGRADATION
• The condition or process of degrading or
being degraded.
• Decline to a lower quality,condition or
level.
PHARMACEUTICAL DEGRADATION
• The incapacity or incapability of a
particular formulation in a specific
container to remain within a
particular chemical, microbiological,
therapeutical, physical & toxicological
specification.
ASPIRIN
Decompose into acetic acid and salicylic acid
giving the acetic acid odour by the break down.
The breakdown is a chemical reaction involving
the collisions of the molecules.This breakdown is
affected by various factors such as presence of
oxygen, acidity, alkalinity, moisture and light. This
breakdown is what we are calling degradation.
TYPES OF PHARMACEUTICAL DEGRADATION
Pharmaceutical degradation is of following type.
It can be divided into three major types:
1. Physical degradation
2. Chemical degradation
3. Microbiological degradation
PHYSICAL DEGRADATION
• It is the degradation which results into the
change of physical nature of drug.
The formulation is totally changed by way of
appearance, organoleptic properties, hardness,
brittleness, particle size.
• Factors effecting physical degradation are as under:
1. Loss of volatile components
2. Loss of H2O
3. Absorption of H2O
4. Crystal growth
5. Polymorphic changes
6. Colour changes
1) Loss Of Volatile Components:
Many drugs and excipients may be lost from
pharmaceutical products at ambient temperature
through vaporization. These Volatile components
such as
Alcohol ,ether,Iodine, volatile oils,Camphor menthol
etc escape from the formulations rendering them
degraded.
•
EXAMPLE: Aromatic waters
Elixirs
Some types of tablets which contain aromatic water (Nitroglycerine tablets)
PREVENTION: Such product should be placed in well closed
containerTemperature should be proper.
2) LOSS OF H20:• Evaporation of water from liquid preparations
will cause concentration of the drug to change
with the possibility of crystilization occurring if
the solubility of the drug in the solvent is
exceeded. Water loss from oil- in – water
creams may result in a decrease in volume and
a surface rubbery feel. Further evaporation of
the water will cause the emulsion to crack.
• Some drugs are efflorescent, which mean they
will lose water to the atmosphere resulting in
a concentration of the drug and overall weight
loss.
• Water loss to the atmosphere can be
prevented by storing the pharmaceutical
product in a well closed container.
EXAMPLES
• Saturated solution: by loss of water they become
supersaturated and precipitate as crystals are formed .
• Emulsions: Loss of water lead to separation of the two
phases and change to other type
• Creams: especially oil/water, they become dry by loss
of water
3) ABSORPTION OF H20(MOISTURE)HYGROSCOPITY
Hygroscopic drugs absorb the water from external
atmosphere causing the physical degradation.
For example, some drugs are delisquent (calcium chloride
and potassium citrate), whereas others are hygroscopic
(glycerol and dry plant extracts). Effervescent powders and
tablets will deteriorate if stored in a moist atmosphere..
EXAMPLE• Powders: Liquification and degradation may occur as
a result of absorption of water
Suppositories which base made from hydrophilic
substances as Glycerin, Gelatin, polyethylene glycol.
The consistency of these forms becomes jelly-like
appearance.
Products should be placed in well-closed container
and in dry place.
4) POLYMORPHISM• Polymorphs are different crystal forms of the same
compound .Polymorphs differs from one another in the
crystal energies, the more energetic ones converting to
the least energetic or most stable one. Different
polymorphs of the same drug may exhibit different
solubility and melting points.
• In polymorphic changes crystal forms are changed.
A stable crystal form loosens.
This may cause alteration in solubility and possibly
crystalline growth in aqueous suspensions.
• Ex Chloremphenicol Palmitate
• Cocoa Butter
5) CRYSTAL GROWTH
• Drugs when loose water,become saturated
and crystal growth occurs.Molecules in the
crystal are not static, they can grow in size and
move when there is a medium to travel.
• Crystallization is enhanced in porous tablets.
EXAMPLE
• Carbamazepine tablets containing stearic
acid form column shaped crystals on
tablet surface during storage at high
temperature.
6) COLOUR CHANGES
Colour changes are of two types.
Loss of colour
Development of colour
1) Loss of colour is due to
· PH change
2) Development of colour is due to
· Exposure to light
• EXAMPLE:
• Phenolphthalein color changes as the Ph changes.It is
colorless in acidic solution and pink in basic.
• PREVENTION:
PH should be adjusted
Exposure to light should be avoided
An attempt has been made to prevent the fading by
incorporating UV light absorbing material.
Physical stability (Cont.)
Formulation
Likely physical instability problems
Effects
Oral solutions
1- Loss of flavour 2- Change in taste 3- Presence of off flavours due to interaction with plastic bottle 4- Loss of dye 5- Precipitation 6- discoloration
Change in smell or feel or taste
Physical stability (Cont.)
Formulation
Likely physical instability problems
Effects
Suspensions 1- settling2- caking3- crystal growth
1-Loss of drug content uniformity in different doses from the bottle
2- loss of elegance.
Physical stability (Cont.)
Formulation
Likely physical instability problems
Effects
Emulsions 1- Creaming
2- coalescence 1- Loss of drug content uniformity in different doses from the bottle
2- loss of elegance
Physical stability (Cont.)
Coalescence
Physical stability (Cont.)
Formulation
Likely physical instability problems
Effects
Tablets Change in:a) Disintegration
timeb) Dissolution profilec) Hardness d) Appearance (soft
and ugly or become very hard)
Change in drug release
Physical stability (Cont.)
Formulation
Likely physical instability problems
Effects
Capsules Change in:a) Appearanceb) Dissolution c) Strength
Change in drug release
Physical stability (Cont.)Formulatio
nLikely physical
instability problems
Effects
Semisolids (Ointments and suppositories)
1. Changes in:a) Particle sizeb) Consistency
2. Caking or coalescence
3. Bleeding
1-Loss of drug content uniformity
2- loss of elegance 3-change in drug release rate.
CHEMICAL DEGRADATION
It is the separation of chemical
compound into elements or simpler
compounds. Change in the chemical
nature of the drug is called as chemical
degradation.
TYPES OF CHEMICAL DEGRADATION
• Types of chemical degradation are
1. Hydrolysis
2. Oxidation
3. Decarboxylation
4. Isomerization
5. Polymerization
HYDROLYSIS• Splitting by water.
• Drugs with functional groups such as esters, amides,
lactones or lactams may be susceptible to hydrolytic
degradation.
• It is probably the most commonly encountered mode
of drug degradation because of the prevalence of
such groups in medicinal agents and the ubiquitous
nature of water.
• Example ASPIRIN:
Aspirin degrade into salicylic acid and
acetic acid giving vinegar like odour.
OXIDATION
• Removal of an electropositive atom, radical or electron,
or the addition of an electronegative atom or radical.
• Types:
Oxidation has two types
· Auto-oxidation
· Photo-oxidation
AUTO OXIDATION
Oxidation in which the oxygen present in the air is
involved.
This process proceeds slowly under the influence
of atmospheric oxygen
e.g. Oil, fats & unsaturated compound can
undergo auto- oxidation
PHOTO OXIDATION
Oxidation in which removal of the electron
is involved with out presence of O2.
This type is less frequently encountered
e.g. It occurs in adrenaline, riboflavin &
ascorbic acid etc.
DECARBOXYLATION
Elimination of CO2 from a compound.Drug
substances having a carboxylic acid group are
sometimes susceptible to decarboxylation,
• 4-Aminosalicylic acid is a good example.
ISOMERIZATION
It is the process by which one molecule is
transformed into another molecule which has
exactly the same atoms, but the atoms are
rearranged 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
• Types of Isomerization:
1) Optical Isomerization
2) Geometrical Isomerization
OPTICAL ISOMERIZATION:
A change in the optical activity of a drug may result as a change in
its biological activity.
It is further divided into:
(i)RACEMIZATION
(ii) EPIMERIZATION
RACEMIZATION:
It involves the optically active form of a
drug into its enantiomorph.
E.X : By the action of heat (-) hyoscyamine
is readily converted to atropine which is
the racemic mixture of (+) & (-)
hyoscyamine.
• Epimerization:
It occur with the compound having more than
one asymetric carbon atom in the molecule.
E.X: Under prolonged storage solution
containing ergometrine is decomposed by
hydrolysis and isomerized to ergometrinine.
GEOMETRICAL ISOMERIZATION:
• Loss of activity due to the difference in potency
exhibited by CIS & TRANS isomers of some organic
compounds.
EX: Active form of VITAMIN A molecule has all trans
configuration.In aqueous solution as a component of
multivitamin preparation,in addition to oxidation
VITAMIN A PALMITATE isomerizes and form 6-mono
cis and 2,6 di-cis isomers,both have low potency.
POLYMERIZATION
• Combination of two or more identical molecules to
form a much larger and more complex molecule.
e.g. Degradation of antiseptic formulations and
aldehydes is due to polymerization. Formaldehyde
solution may result into formation of white deposit
when stand in cold.
PHOTO DEGRADATION Photodegradation is the process by which light-
sensitive drugs or excipient molecules are
chemically degraded by light, room light or
sunlight.
PHOTOLYSIS:
It is defined as decomposition of a drug by light.
Photodegradation of Primaquine & chloroquine give
different products by various pathways.
Sodium nitropruside stable for 1 year if protected
otherwise may degrade after 4 hours.
It can be prevented by :
Suitable packing in amber coloured bottles.
Cardboard outers
Aluminium foil over wraps.
Stabilization of drugs against hydrolysis, oxidation and photolysis:
TEMPERATURE: All the drug products are stored at suitable
temperatures to avoid thermal acceleration of decomposition.
LIGHT: Light sensitive materials are stored in ambered
colour bottles
Humidity Packing materials are chosen (usually glass and
plastic) to prevent exposure of drug products to high humid condition.
Oxygen Proper packing keeping the oxygen content of
the solution less and leaving very little head space in the bottle above the drug products are methods to fight against oxidation
MICROBIAL DEGRADATION
• Contamination of a product may sometimes
cause a lot of damage and sometimes may not
be anything at all. Thus it is dependent on the
type of microbe and its level of toxicity it may
produce.
If parenterals or opthalmic formulations are
contaminated, it may cause serious harm.
• Pyrogens which are the metabolic products of
bacterial growth are usually lipo
polysaccharides and they represent a
particularly hazardous product released by
gram negative bacteria. If administered
inadvertently to a patient they may cause
chills and fever.
PREVENTION OF MICROBIAL DEGRADATION
• suitably designing the containers
• usually using single dose containers
• sticking to proper storage conditions
• adding an antimicrobial substance as preservative.
METHOD FOR DETECTING CHEMICAL/ PHYSICAL DEGRADATION
• THERMAL ANALYSIS: Following methods can be used for
detection,
DIFFERENTIAL SCANNING CALORIMETRY (DSC) DIFFERENTIAL THERMAL ANALYSIS (DTA) DIFFERENTIAL THERMOGRAVIMETRY (DTG)
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