STABILITY STUDIES WITH SPECIAL REFERENCE TO UNANI MEDICINE

2. STABILITY STUDIES WITH SPECIAL
REFERENCE TO UNANI MEDICINE
Presented By
Md. Naquibuddin
(P.G Scholar)
Under the guidanceof,
Dr. Khaleequr Rahman
(Lecturer)
DEPARTMENT OF ILMUL SAIDLA
NATIONAL INSTITUTE OF UNANI MEDICINE, BANGALORE

3. Introduction
• Nothing in this universe is immortal, all things
that have form eventually decay.
• Medicinal products also degrade with time
thus significance and indispensability of
stability testing in development of dosage
forms/formulation is well recognized.
• Stability testing is necessary to ensure that the
product is of acceptable quality throughout its
entire storage period.

4. • The purpose of stability testing is to provide
evidence on how the quality of a drug substance
varies with time under the influence of various
environmental factors.
• Recent efforts by the International Conference on
Harmonization with regard to stability have
brought an increased regulatory scrutiny at very
low level.
• Ministry of Health and Family Welfare, Dept. of
AYUSH also admitted that the potency of ASU
preparations looses/reduces after a certain
period of time. Hence display of expiry date on
container or package has been made mandatory.

6. • Unani literature describes shelf life as that period
within which the drug is able to keep its
temperament, constituents and structural
constitution in equilibrium, which may be judged
by means of observing its organoleptic
characteristics.
• Until these characteristics are intact the drug is
said to be stable, and in case of any deviation it is
assumed that the drug has lost its stability.
• The first person to mention about stability OF
DRUG was none other than Buqrat (460-377BC).
He stated that if gum is added to marham
(ointment) it remains stable for about twenty
years.

7. Unani literature displays stability of
different plant parts as:
• Flowers and leaves: They remain stable for 6
months and after one year are considered
useless, but in case of proper storage their
stability can be maintained for two years.
• Fruits: These remain stable only up to their
respective seasons and even less, bahi (Pyrus
communis), unnab (Zizyphus sativus) and other
watery fruits do remain stable for only one
month, but those with less oil content can be
used for two to three years.

8. • Seeds: Depending upon the content of oil and
fats seeds remain stable for more or less
duration, those with less oil load like zeera
(Carum carvi), badiyan (Foeniculum vulgare)
retain their life for 2 to 3 years and those with
more oil and fat content like tukhme
khashkhash (Papaver somniferum) and
tukhme tarbooz (Citrullus vulgaris) remain
stable for not more than a year.
• Kernels: Like akhrot (Jugulans regia), badam
(Prunus amygdalus) and chilghoza (Pinus
gerardiana) remain stable for about a year.

9. • Branches, barks and roots: Their stability varies
from plant to plant and characters like their
hardness, softness, solid or spongy attributes
which are leading factors responsible for duration
of their stability. Roots like that of adrak (Zingiber
officinale), chobchini (Smilax china), narkachur
(Zingiber zerumbet) and sheqaqul misri
(Pastinaca secacul) remain potent for a year while
those of qust (Saussurea lappa) and waj turki
(Acorus calamus) remain stable for 10 years. As
far as barks like darchini (Cinnamomum cassia)
and taj (Cinnamomum tamala) are concerned,
their shelf life has been noted down as 2 years
which is the average shelf life of barks. But there
may be variation depending upon amount of
moisture content.

10. • Gums: Like gonde kateera (Cochlosperum religiosum),
luk (Coccus lacca), and dammul akhwain (Dracaena
cinnabari) have shelf life up to 3 years which is usual
age of gums.
• Extracts: Their age is up to 2 years like that of rasaut
(Berberis aristata), aqaqiya (Acacia arabica) etc.
• Oils: They being liable to decomposition and rancidity
have less shelf life. Oils with barid mizaj like roghane
kaddu, roghane kahu and roghane khashkhash are less
stable than those roghaniyat, which are having haar
mizaj like roghane zaitoon, roghane kunjad, roghane
kataan and roghane balsan which remain stable for
about 2 years. Among haar roghaniyat, roghane balsan
stands at top in terms of retaining shelf life and as for
as roghane zaitoon is concerned its age is said to
increase with time and can remain potent for 4 years.

11. Drugs and Cosmetics (Amendment)
Rules, 2005
• "161B: - The date of expiry of Ayurveda,
Siddha and Unani (ASU) medicines shall be
conspicuously displayed on the label of
container or package of an Ayurvedic, Siddhas
and Unani drugs, after which they shall not be
in circulation. Shelf-life for Ayurveda, Siddha &
Unani (ASU) medicines shall be as follows:

12. Shelf life or expiry date for Unani
System of Medicines
S.No.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Name of the Group of Medicine
Habb (Pills)
Qurs (Tablets)
Majoon / Dawa
Khamira
Itrifal
Tiryaq
Laooq
Laboob
Halwa
Mufarreh / Yaqooti
Burood / Surma / Kohal
Kushta
Raughaniyat
Marham / Zimad / Qairooti
Ayarij / Sufoof
Safoof (Namak wala / containing salt)
Shelf life / Expiry date
2 Years
2 Years
2 Years
2 Years
3 Years
2 Years
1 Year
1 Year
1 Year
2 Years
3 Years
5 Kushta
2 Years
2 Years
1 Years
6 Months

13. S.No.
17.
18.
19.
20.
21.
22.
23
24.
Name of the Group of Medicine
Sharbat / Sikanjabeen
Jawarish
Capsule
Arq
Qutoor
Nabeez
Murabba
Tila
Shelf life / Expiry date
2 Years
2 Years
2 Years
1 Year
1 Year
5 Years
1 Year
2 Years

14. • Note: The principal rules were published in
the Gazette of India, vide, Notification
number F.29-10/45-H dated 21.12.1945 and
last amendment vide number G.S.R. 664,
dated 14.11.2005.

15. Controversy in Shelf life mention in
Classical literature and D & C rule.
• Shelf life mention in classical literature were evaluated
only on subjective parameter or parameters available
in those time, which may not qualify present scientific
methods.
• Shelf life mentioned in D & C rule are abstract of
various textual references.
• Shelf life mentioned in D & C rule are based on dosage
form.
Where as it is the responsibility of manufacturer to asses
shelf life of their products. Shelf life of a drug product
may vary from manufacturer to manufacturer or
industry t industry.

17. Stability
• The capacity or the capability of a particular
formulation in a specific container to remain
with in particular chemical, microbiological,
therapeutically, and toxicological specifications.
Or
• Extent to which a product retains with in
specified limits and throughout its period of
storage and use ( i.e. shelf life). (USP)

18. • Stability is officially defined as the time during
which the drug product retains the same
properties and characteristics that it possessed at
the time of manufacture.
• Drug stability refers to the capacity of a drug
substance or product to remain within established
specifications of identity, strength, quality, and
purity in a specified period of time.

19. Stability studies are incorporated at all stages of drug product life cycle from
early stages of product development to late stage follow-up stabilities. In
particular the life cycle can be segregated into 6 different stages.
• Stage 1- Early stage stress and accelerated testing
with drug substances.
• Stage 2- Stability on pre-formulation batches. (Pilot
Batch)
• Stage 3- Stress testing on scale-up batches. (Regular
production batch)
• Stage 4- Accelerated and long term testing for
registration purposes.
• STAGE 5- On-going stability testing.
• STAGE 6- Follow-up Stabilities.

20. Regulations and Guidances
• The ICH (International Conference on
Harmonization) Guidelines Q1A(R2) “Stability
testing of new drug substances and products” is
the “gold standard” for conducting stability
studies. This is valid for “new drug substances or
drug products” that are sufficient for a registration
application.

21. ICH GUIDELINES FOR STABILITY
STUDIES
• Q1A- Stability testing of new Drug
Substances and Products.
• Q1B- Stability Testing : Photo stability
Testing of New Drug Substances and
products.
• Q1C- Stability Testing for new Dosage
forms.
• Q1D- Bracketing and Matrixing Designs for
Stability Testing of New Drug Substances
and products.
• Q1E- Evaluation of stability data.
• Q1F- Stability data package for registration

22. Why Stability studies are necessary ?
• Chemical degradation of the product leads to
lowering of the concentration of the drug in
the dosage form.
• Toxic products may be formed, due to
chemical degradation of the active ingredient.

23. Advantages of Stability studies
• Assurance to the patient
• Economic considerations
• Legal requirement.

24. OBJECTIVE OF STABILITY STUDY
• To determine maximum expiration date/ shelf
life.
• To gather information during pre-formulation
stage to produce a stable product.
• To provide better storage condition.
• To determine the packaging components.
• To establish retest period of pharmaceuticals.
• To establish transport condition.

25. Factors affecting Drug Stability
• Storage condition.
• Interaction between the API and excipient.
• Formulation Development.
• Selection of dosage form.
• Manufacturing process of drug product.
• Selection of container closure packaging
system.

26. • Effect of storage (temperature, humidity and
light).
• Selection of marketing image.
• Handling of the finished products.

27. Types
• Three types of Stability Studies
• Accelerated
Studies designed to know the short term Excursions of
temperature on the drug Substances.
• Intermediate
Studies conducted, incase of failure in accelerated
studies and the conditions of temperature and humidity
are in between long term and accelerated.
• Long term
Studies designed to check the stability of the drug
substnace.

28. Stability Protocol
Study Storage Condition
Minimum time
period covered by
data at submission
Long term
(Ambient)
25o C ± 2o C
60%RH ± 5%
12 Months
Intermediate
(Controlled)
30o C ± 2o C
60%RH ± 5%
6 Months
Accelerated 40o C ± 2o C
75%RH ± 5%
6 Months

30. LONG TERM STUDY
• Frequency of testing in case of long-term
study should normally be every three months
over the first year, every six months over the
second year and annually thereafter.

31. ACCELERATED STUDY
• In case of accelerated study a minimum of
three time points including the initial and final
time point is necessary e.g 0, 3 and 6 months

32. INTERMEDIATE STUDY
• In case of intermediate study four time points
are proposed.

33. TYPES OF STABILITY THAT MUST BE
CONSIDERED FOR ANY DRUG
• Physical Stability:
– It includes appearance, palatability ,uniformity
,dissolution and suspendability etc.
• Chemical Stability
– Each active ingredient retains its chemical integrity
and labeled potency within the specified limit.
• Microbiological Stability
– Retained according to specified requirement.
• Therapeutical stability
– Therapeutic activity remains unchanged.
• Toxocologic Stability
– No significant increase in toxicity occurs.

34. TYPES OF STABILITY THAT MUST BE
CONSIDERED FOR UNANI DRUGS
• Alternative medicine drugs are based on multi
component, hence only chemical stability
evaluation even using marker compound is
not sufficient.
• Therefore, apart from physical and microbial
characters, therapeutical stability to confirm
whether therapeutic activity remains
unchanged, is the most important stability
parameter.

35. Limits for degradation
• The question of how much degradation is
acceptable has been the topic of many
discussions amongst pharmaceutical scientists.
Degradation of drug substances between 5% and
20% has been accepted by pharmaceutical
scientist.
• Most of the pharmaceutical scientists think 10%
degradation is acceptable for pharmaceutical
molecules and stability limits of 90% of label
claim is common.

36. The ICH guideline fixed only 5% variation limit,
that is most stringent stability guideline.
• No such limits for physiochemical changes,
loss of activity or degradation during shelf life
have been established for some individual
types or groups of biological products.
• Till date no reliable stability data were
generated for alternative medicine drugs
hence no such limit are fixed for the same.
• However limitations mentioned in stability
guidelines for modern medicine may be used.

37. INTERPRETATION
• Joel Devis rule: If drug is stable for 3 month at
40oC and 75% RH its stability period is equivalent
to 24 month at 25 C.
• As per the shelf life recommendation for
supplement if product is stored 10oC above the
room temperature for a specific period its shelf
life will be estimated as 2x storage time duration.
• Grimm’s statement:
= 3.3x period of accelerated stability condition.