STABILITY OF

DRUGS
Dra. Kartiningsih, M. Si., Apt
Lusiana Ariani, M.Farm., Apt
References
1. Cartensen, J.T. Drug Stability Principle and Practise, Marcel
Dekker Inc., 1990
2. Connors,K.A., Gordon L.A., Valentino J.S., Chemical Stability of
Pharmaceutical, 2nd ed. Wiley Interscience, 1986
3. Yoshioka, Sumi and Stella, Valentiono J. Stability of drugs and
dosage forms. New York: Kluwer Academics Publisher. 2002.
4. WHO, Accelerated Stability Studies of Widely Used
Pharmaceutical Substance Under Simulated Tropical
Conditions, Interpham Press Inc.
5. Cara Pembuatan Obat yang Baik, Badan Pengawasan Obat
dan Makanan Indonesia
STABILITY OF DRUGS
• Stability: is the capacity of a drug product to remain within
specifications established to ensure its identity, strength
quality and purity.

• Instability may cause

- Undesired change in performance, i.e.
dissolution/bioavailability
- Substantial changes in physical appearance of the dosage
form
- Causing product failures
• A drug is produced in large quantities and takes a long time to
reach the patients. If the drug is not stable, the dosage will be
reduced and / or can produce toxic and harmful products to
patients.
Objectives of Stability Test

• To know how the quality of product changed

caused by environment
• To determine shelf life and expired date of the
dosage forms.
• To give recommendation for production,
distribution and storage of the product.
 Function of Stability Data:
• Raw material stability data gives
information about:
- A kind of dosage form
- Formulation of the dosage form
- Production methods
- Storage of the material
- Packaging material for product
- Expired date from raw material
and product
Function of Stability Data:
• Stability Data of Dosage Form gives information
about:
- Storage condition of product
- interval test of active pharmaceutical ingredients
from dosage form
- Expired date of the product
Types of stability studies:

۞ Physical

۞ Chemical

۞ Microbiological

۞ Pharmacological

۞ Toxicological
Physical stability
• Physical stability implies that:
- The formulation is totally unchanged throughout
its shelf life and has not suffered any changes by
way of appearance, organoleptic properties,
hardness, brittleness, particle size etc.

- It is significant as it affects:
pharmaceutical elegance
drug content uniformity
drug release rate.
Physical stability (Cont.)

Formulation Likely physical Effects

instability problems

Oral solutions 1- Loss of flavour Change in

2- Change in taste smell or
3- Presence of off flavours feel or
due to interaction with taste
plastic bottle
4- Loss of dye
5- Precipitation
6- discoloration
Physical stability (Cont.)
Formulation Likely physical Effects
instability problems
Parenteral 1. Discoloration due to photo Change in
chemical reaction or appearance
solutions oxidation and in bio-
2. Presence of precipitate due to availability
interaction with container or
stopper
3. Clouds due to:
(i) Chemical changes
(ii) The original preparation of a
supersaturated solution
Physical stability (Cont.)

Formulation Likely physical Effects

instability problems

Suspensions 1- settling 1-Loss of drug

2- caking content
3- crystal growth uniformity in
different doses
from the bottle

2- loss of
elegance.
Physical stability (Cont.)

Formulation Likely physical Effects

instability problems
Emulsions 1- Creaming 1- Loss of
2- coalescence drug content
uniformity in
different doses
from the bottle

2- loss of
elegance
Physical stability (Cont.)

Coalescence
 Physical stability (Cont.)
Formulation Likely physical Effects
instability problems
Semisolids 1. Changes in: 1-Loss of drug
(Ointments a) Particle size content
and b) Consistency uniformity
suppositories)

2. Caking or 2- loss of
coalescence elegance

3. Bleeding 3-change in
drug release
rate.
 Physical stability (Cont.)

Formulation Likely physical Effects

instability problems
Tablets Change in: Change in
a) Disintegration time drug release
b) Dissolution profile
c) Hardness
d) Appearance (soft and
ugly or become
very hard)
 Physical stability (Cont.)

Formulation Likely physical Effects

instability problems
Capsules Change in: Change in
a) Appearance drug release
b) Dissolution
c) Strength
Chemical stability:

• Chemical stability implies:

The lack of any decomposition in the chemical
that is incorporated in the formulation as the drug,
preservatives or any other excipients.

This decomposition may influence the physical

and chemical stability of the drug
Chemical Degradation

• Chemical degradation caused by:

- change in potential
- decreased of active compound
- decreased of excipient, ex: antioxidant and preservative
- the formation of toxic decomposition

Chemical degradation could explain by chemical kinetics

Chemical kinetics

 CH3COOH + 2 C2H5OH 2CH3CO2C2H5 + H2O

Slow reaction

HCl + NaOH NaCl + H2O

Fast reaction

So, the chemical kinetic based on the reaction speed, which is the
principle of chemical kinetics.
Microbiological Stability
❑ Microbiological stability is a condition where the preparation
remains free from microorganisms to a certain time limit.
❑ There are various types of active drug substances, additives and
various dosage forms and methods of administration of drugs.
❑ Each substance, method of administration and dosage form has
its own physical-chemical characteristics and is generally
susceptible to microorganism contamination that can affect the
quality of the preparation because it has the potential to cause
disease, unexpected effects on therapy or use of drugs and
cosmetics.
Physical-Chemical Properties Factors Active substances and
additional substances
Chemical physical properties of active substances and additives
can affect the stability of the microbiology of the preparation.
Substances that are hygroscopic or hydrophilic are susceptible to
microorganism contamination. This is related to the presence of
water which is a growth medium for microorganisms.

Contamination Factors from Raw Materials and Processes

Natural raw materials in water that are free of powder or granules
can be a place for microorganisms, viruses or microbial toxins to
grow. Analysis of these ingredients can indicate the presence of
bacteria, Clostridium spores, Staphylococci, mold and especially
fungal / fungal toxins.
The possibility of their existence may have existed since the
production preparation stage. Natural ingredients extracted,
produced or supplied in liquid dough are also susceptible to
microorganism contamination.
Pharmacology Stability
The activity of bioactive compounds is caused by the interaction
between drug molecules and the molecular parts of biological objects
which are specific reseptor.

To be able to interact with specific receptors and generate specific

activities, bioactive compounds must have a specific steric structure
and load distribution. The basis of bioogical activity is complex chemical
processes from the moment the drug is given until a biological response
occurs.
Toxicological Stability
Toxicological stability is a measure that shows the resistance of a
substance to chemical, physical, microbiological and
pharmacological influences that do not cause a significant increase in
toxicity.

EFFECT OF TOXICITY

• Acute toxic effects, have a direct correlation with absorption of toxic

substances.
• Chronic toxic effects, small amounts of toxic substances absorbed over a
long period of time, accumulate, reach toxic concentrations eventually
poisoning.