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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