Prepared

1. Welcome to Our Presentation
Topics: Drug Stability
Group Number: 11
Course Title: Pharmaceutical Chemistry & Pharmaceutics
Course Code: ACCE 4131
Department of Applied Chemistry & Chemical Engineering,
Rajshahi University

2. What is Drug Stability?
Drug stability means the ability of the
pharmaceutical dosage form to maintain the
physical, chemical, therapeutic and microbial
properties during the time of storage and
usage by the patient.
It is measured by the rate of changes that take
place in the pharmaceutical dosage forms.

3. Objectives of Drug Stability
1. To provide knowledge of the physical-chemical
principles and terminology used in discussing
stability problems.
2. To create awareness of the general problems of
drug stability so that expiration dates and other
special storage requirements will have more
meaning.
3. To show how drug stability may be predicted.
4. To assist in prediction of incompatibility.
5. To show how stability of drugs in view may
influence their therapeutic effect.

4. Factors Influencing Drug Stability
Following factors are influencing drug stability:
1. Temperature,
2. pH,
3. Moisture,
4. Light,
5. Pharmaceutical dosage forms,
6. Concentration,
7. Drug incompatibility,
8. Oxygen

5. Influence of Temperature

6. Influence of pH
Acidic and alkaline pH influence the rate of decomposition of
most drugs. Many drugs are stable between pH 4 and 8. Weekly
acidic and basic drugs show good solubility when they are
ionized and they also decompose faster when they are ionized.
So if the pH of a drug solution has to be adjusted to improve
solubility and the resultant pH leads to instability then a way out
of this tricky problem is to introduce a water miscible solvent
into the product. It will increase stability by:
- suppressing ionization
- reducing the extreme pH required to achieve solubility
- enhancing solubility and
- reducing the water activity by reducing the polarity of the
solvent. For example, 20% propylene glycol is placed in
chlordiazepoxide injection for this purpose.

7. Influence of pH cont……..
• Reactions catalyzed by pH are monitored by measuring
degradation rates against pH,keeping temperature, ionic
strength and solvent concentration constant. Some buffers
suchas acetate, citrate, lactate, phosphate and ascorbate
buffers are utilized to prevent drastic change in pH.
• Sometimes pH can have a very serious effect on
decomposition. As little as 1 pH unit change in pH can
cause a change of ten fold in rate constant. So when we are
formulating a drug into a solution we should carefully
prepare a pH – decomposition profile and then formulate
the solution at a pH which is acceptable physiologically and
stability-wise also.

8. Effects of other factors
Effect of Moisture:
a.Water catalyses chemical reactions as oxidation, hydrolysis and
reduction reaction
b. Water promotes microbial growth.
Effect of Light: Light affects drug stability through its energy or
thermal effect which lead to oxidation.
Effect of Pharmaceutical dosage forms: Solid dosage forms are
more stable than liquid dosage forms for presence of water.
Effect of Concentration: rate of drug degradation is constant for
the solutions of the same drug with different concentration. So,
ratio of degraded part to total amount of drug in diluted
solution is bigger than of concentrated solution.

9. Effects of other factors
Drug incompatibility: reactions between components
of pharmaceutical dosage forms it self or between
these components and cover of the container .
Oxygen: exposure of drug formulations to oxygen
affects their stability

10. Classification of Drug Stability
Drug stability can be classified into following
types:
1. Physical Stability,
2. Chemical Stability, &
3. Microbiological Stability.

11. Physical Stability of Drugs
Physical instabilities possibilities are:
1.Crystal formation in pharmaceutical preparations:
Causes:
a. Polymorphism phenomena: i.e. Chloramphenicol
(change of amorphous to crystalline form.)
b. Saturated solution: by different temperature
precipitation of solute may occur.
c. In suspension: when very fine powder is used a part of
suspending agent will dissolve then precipitate as crystal.

12. Physical Stability of Drugs cont….
2. Loss of volatile substances from pharmaceutical dosage forms:
Examples: aromatics water,elixirs,spirits etc.
3. Loss of water:This can be seen in the following dosage forms:
a. Saturated solution: by loss of water they become supersaturated and
precipitate as crystals is formed.
b. Emulsions: Loss of water lead to separation of the two phases and
change to other type.
c. Creams: especially oil/water, they become dry by loss of water
d. Ointments: especially aqueous base ointments.
Humectants is added to the previous dosage forms which
defined as hydrophilic substances added to aqueous phase to
absorb water from atmosphere and prevent its loss from the
dosage forms.Examples: Glycerin

13. Physical Stability of Drugs cont….
4. Absorption of water:This phenomena can be seen in the
following pharmaceutical forms:
a. Powders: Liquification and degradation may occur as a
result of absorption of water.
b. Suppositories which base made from hydrophilic
substances as Glycerin, Gelatin, polyethylene glycol.
The consistency of these forms becomes jelly-like appearance
5.Change in crystalline form:
Example: Cocoa butter which is capable of existing in four
polymorphic forms.

14. Chemical Stability
Each active ingredient retains its chemical
integrity and labeled potency within the
specified limits.
Chemical instabilities possibilities are:
1. Hydrolysis
2. Oxidation
3. Isomerization
4. Photochemical decomposition
5. Polymerization

15. Hydrolysis
Drugs susceptible to hydrolytic degradation
How can we tell whether a drug is likely to be susceptible
to this type of degradation?
If the drug is a derivative of carboxylic acid or contains
functional groups based on this moiety, for example an
ester, amide, lactone, lactam, imide or carbamate, then we
are dealing with a drug which is liable to undergo
hydrolytic degradation.
Hydrolysis is frequently catalysed by hydrogen ions
(specific acid-catalysis) or hydroxyl ions (specific base-
catalysis) and also by other acidic or basic species that are
commonly encountered as components of buffers.

16. Oxidation
Oxidation involves the removal of an electropositive
atom, radical or electron, or the addition of an
electronegative atom or radical.
Oxidative degradation can occur by autoxidation, in
which reaction is uncatalysed and proceeds quite
slowly under the influence of molecular oxygen, or
may involve chain processes consisting of three
concurrent reactions – initiation, propagation and
termination.

17. Isomerization
Isomerisation is the process of conversion of a drug
into its optical or geometric isomers, which are often
of lower therapeutic activity. Since the various
isomers of a drug are frequently of different activity,
such a conversion may be regarded as a form of
degradation, often resulting in a serious loss of
therapeutic activity.
For Example:
In acidic conditions the tetracyclines undergo
epimerisation at carbon atom 4 to form an
equilibrium mixture of tetracycline and the epimer,
4-epi-tetracycline. The 4-epi-tetracycline is toxic and
its content in medicines is restricted to not more

18. Photochemical decomposition
Many pharmaceutical compounds, including the
phenothiazine tranquillizers, hydrocortisone,
prednisolone, riboflavin, ascorbic acid and folic acid,
degrade when exposed to light. As a result there will be
a loss of potency of the drug, often accompanied by
changes in the appearance of the product, such as
discoloration or formation of a precipitate.
Photodecomposition might occur not only during
storage but also during use of the product. For
example, sunlight is able to penetrate the skin to a
sufficient depth to cause photodegradation of drugs
circulating in the surface capillaries or in the eyes of
patients receiving the drug.

19. Polymerisation
Polymerisation is the process by which two or more
identical drug molecules combine together to form a
complex molecule.
It has been demonstrated that a polymerization process
occurs during the storage of concentrated aqueous
solutions of aminopenicillins, such as ampicillin sodium.
The hydrate of formaldehyde, HOCH2OH, may under
certain conditions polymerise in aqueous solution to
form paraformaldehyde, HOCH2(OCH2)nOCH2OH, which
appears as a white deposit in the solution. The
polymerization may be prevented by adding to the
10 –15% of methanol.

20. Microbiological stability
1. Contamination from microorganisms is a
big problem for all formulations
containing moisture but it can be a
bother in solid dosage forms also if some
natural polymers are used because many
natural polymers are fertile sources of
microorganisms.
2. In the type of hygienic manufacture
carried out today where “Quality
Assurance” is a prerequisite as per the
GMP procedures, there are definite
procedures to prevent microbial
contamination in all formulations.

21. Source of microbial contamination
Source Name Microbial life
Water Low demand gram-negative groups:
Pseudomonas,
Xanthamonas, Flavobacterium, Achromobacter
Air Mould spores: Penicillium, Mucor, Aspergillus
Bacterial spores: Bacillus spp. Yeasts
Earths Anaerobic spore formers: Clostridium spp
Pigments Salmonella
Raw materials Micrococci
Starches Coliforms
Gums Actinomyces
Animal products Salmonella, Coliforms
Personnel Coliforms, Staphylococci, Sterptococci,
Coryembacteria

22. Adverse Effect of Instability of
Drug

23. Steps to increase drugs
stability
By keeping all the factors
influencing stability at optimum
level drug stability can be increased

24. THANK YOU