The document discusses self life and stability studies of formulations in Indian Systems of Medicine (ISM). It provides background on the three main systems of ISM - Ayurveda, Siddha, and Unani. It then discusses the importance of stability testing and shelf life determination to ensure safety and efficacy of ISM products over time. Key concepts from classical ISM texts on shelf life are presented. Guidelines for conducting stability studies outlined in the Ayurvedic Pharmacopoeia of India are summarized, including storage conditions, testing methods, evaluation criteria and protocols.

1. Self Life & Stability Studies
of ISM Formulations
Presented by : Chhavi Singh
M. Pharm 1 year 2 Sem
Enroll. No. 155/MPG/SPS/2020

2. The Indian Systems of Medicine (ISM)
• The Indian Systems of Medicine (ISM) consist of Ayurveda, Siddha and Unani (ASU).
• These traditional or alternative medicine is widely used in the prevention, diagnosis and
treatment of an extensive range of ailments.
• The medicinal products of ASU system of medicine include single herb or polyherbal
formulations with or without mineral drugs and/or drug of animal origin.
• Some of these systems are indigenous and others have over the years become a part of
Indian tradition.
• Ayurveda is the sacred system of health care, originated in India whereas Unani
medicine originated in Greece and was introduced to India by the Arabs.
• Siddha system of medicine is practiced in Tamil speaking parts of India and abroad.

3. • Stability is an important parameter for safety and efficacy of the product.
• There is an increasing concern for shelf life and stability in Ayurveda, Siddha and Unani system of medicine
developed in Asia over the centuries.
• Concept behind expiry means that after a certain period, the substance that is used as medicine
undergoes changes, which make it ineffective. That period is known as expiry date or shelf life in modern
system of medicine.
• This concept was described in 14th century by Acharya Sharangdhar as Saviryata Awadhi in his textbook
Sharangdhar Samhita.
• The API (The Ayurvedic Pharmacopoeia of India) Part I, Vol. VIII prescribe guidelines for stability testing
and shelf-life determination for new and existing Ayurvedic drugs including Siddha and Unani medicine.
• A product can be considered to-be stable if “no significant change” occurs during at any time of testing.
• During transfer of product from manufacturer to user, the variations in external factors may create
changes in stability. In order to obtain full therapeutic efficacy, it is mandatory that the product should be
stable at user end.
Concept of Stability

4. • STABILITY : Capability of a specific formulation in a
particular container/closure system to remain within its
physical, chemical, microbiological, toxicological,
therapeutic specifications at a defined storage condition.
• Stability is expressed in terms of shelf life.
• The shelf life : The shelf life of a product can be defined as
the time duration up to which it is expected to retain 90%
of its active ingredients (label claim) when stored in
recommended condition.
• Expiration date : Date placed on the container label of a
drug product designating the time prior to which the
product is expected to remain within the approved shelf-
life specification if stored under defined conditions and
after which it must not be used.
• The purpose of
stability testing is to
provide evidence of
how the quality of a
pharmaceutical
product changes with
time due to impact of a
variety of
environmental factors,
namely, temperature,
humidity, and light and
product-related
factors, namely,
container closure
system and packaging
materials.

5. The concept of shelf life can be traced from classical texts
AYURVEDIC DOSAGE FORM SHELF LIFE
(SAVIRYTA AVADHI) AS PER CLASSICS

6. The concept of shelf life can be
traced from Unani classical texts
• Similarly, the texts of Unani medicine provide the concept of shelf life.
• As per Jalinoos’ book Kitabul Murakkabath, the potency of Safoof (powder) is not more
than 2 months and shelf life of Habub and Aqras (pills and tablets) is more than that of
Safoof whereas shelf life of Sharbat (syrup) is about one year10 .
• Arab physician Ali Ibne-Abbas Majoosi in his compilation Kitab-Al-Mulki, mentions shelf
life of Aqraas Ashqueel, Aqraas Afaai, Tiryaaq Arba and Tiryaaq Shalisa from two months
to two years and shelf life of Majoon Kibrit from 6 months to three years.
Cont.

7. Shelf Life of Ayurvedic Medicine as per D and C
Amendment Rules, 1945

8. Types of Stability Testing Methods
Five types of stability testing methods :
1. Accelerated testing - Product is subjected to a several high temperatures, humidity, light intensity, etc., that accelerates
degradation and the amount of heat required to degrade the product is determined so as to predict the shelf life. Usually
used for products with longer shelf life.
• Based upon Arrhenius equation that describes the relationship between storage temperatures and deterioration rate.
2. Real time (long-term) testing - Performed for longer duration to allow significant degradation of the product under
specified storage conditions.
3. Intermediate testing - Mainly conducted when the accelerated studies for general case failed to meet the acceptance
criteria and are designed to moderately increase the rate of degradation for a drug intended to be stored long-term at
25°C.
4. Stress testing - Includes the effect of temperature (above that used in accelerated study), humidity (e.g., ≥75% RH),
oxidation, photolysis and hydrolysis.
5. Forced degradation testing- Performed with objective to provide intrinsic stability assessment of the drug, to elucidate
the possible degradation pathways by identifying the likely degradation products and to have an idea of the stability of
the analytical process applied for the drug.

9. Climatic Zones for
Stability Testing
For stability testing purpose, the whole world has been divided
into four zones depending upon the environmental conditions and
are derived on the basis of mean annual temperature and relative
humidity data in these regions.
ICH climatic zones and long-term stability conditions

10. Protocol for Stability Testing
The protocol is a document describing the basic components of a well-controlled stability study which depends on
the type of drug substance, whether the drug is new or is already in the market and in which climatic zone, the
product is proposed to be marketed.
1. Selection of batches and samples - A random sample from pilot or production batches that may involve a
single batch or 2-3 batches.
2. Test attributes - Tests that monitor the quality, potency, purity, and identity that are expected to vary upon
storage are chosen as stability tests.
3. Analytical procedures - Procedures given in the official compendia should be followed and if alternate
methods are to be used, they need to be duly validated.
4. Acceptance criteria - Should be fixed beforehand in the form of statistical limits for the results manifested in
computable terms and pass or fail for qualitative tests.

11. 5. Storage conditions - Based upon the marketing climatic zone of the drug.
6. Storage period - Generally extend from min. of 3 or 6 months in accelerated and stress testing and up to 12, 18,
or 60 months in ongoing or follow-up stability testing.
7. Testing frequency - Should be sufficient to establish the stability profile of the drug.
8. Sampling plan - Involves devising for the number of samples to be placed in the stability chambers and taking
out of the charged batch so as to cover the entire study.
9. Container closure system - The testing in actual containers as well as closures scheduled for marketing, are to be
tested separately with proper orientation of storage of containers.
10. Evaluation - The data on quantitative attribute is analyzed to determine the time duration at which 95% one-
sided confidence limit for the mean curve intersects the acceptance criterion.
11. Statements, labeling - A storage statement, retest period, and re-test date based on the stability evaluation of
the drug substance should be established for the labeling.

12. Stability testing storage conditions for
drugs as per ICH and the WHO
International Conference on Harmonization guidelines details
out the methods of quality assessment parameters as a means
of evaluating shelf life which should be applied to ASU drugs
also.

13. Test Schedule for Stability Testing of New Products

14. Stability Testing and Shelf-life Determination for New and Existing
Ayurvedic Drugs according to Ayurvedic Pharmacopoeia of India
Two approaches can be followed to monitor the stability of the product :
• The first approach is to store the samples of same batch material at standard
storage and accelerated storage conditions and test them periodically. Based on the
evaluation of the results, the expiry date or shelf life may be determined.
• The second approach is to select samples from batches manufactured over a
period of last five years spanning six months and evaluate them simultaneously.
Based on the result obtained the expiry date or shelf life may be determined. This
approach is applicable for existing products which do not have yet a declared shelf
life. This approach has been referred in scientific literature as the “cross sectional
approach”.

15. • Formal stability studies should be conducted on at
least three primary batches.
• The primary batches should be of the same
formulation as proposed for marketing.
• For new products, the batches should be
manufactured to a minimum of pilot scale.
• Pilot batches which are at least 1/10 of the
commercial batch size can be used.
• Stability to be performed on each individual strength
and container size of the product unless bracketing
and matrixing is applied.
• For cross sectional approach at least two batches per
year to be selected. E.g. if stability to be evaluated for
four years eight batches should be selected.
Selection of batches
Container and closure
system
The stability studies should
be conducted on the
dosage form packaged in
the container and closure
system proposed for
marketing.

16. • Specification is a list of tests, reference to analytical procedures and proposed acceptance criteria.
• Stability study should include testing of those attributes of the drug that are susceptible to change
during storage and are likely to influence quality, safety, and/or efficacy.
• The testing should cover as appropriate, the physical, chemical, biological, and microbiological
attributes.
• Validated stability-indicating analytical procedures should be applied.
• The physical parameters included in the specification need not be limited to color, odor,
appearance, shape and taste only.
• The chemical parameters should include color reaction, pH value, weight variation, disintegration,
bulk density, extractive values, estimation of active or marker or category compound by suitable
methods and chromatographic profiling.
• A suitable bioassay may be employed wherever possible.
• The limits of acceptance for the products should be those specified in pharmacopoeia.
Specification

17. Testing frequency
• For long term studies frequency of testing should be sufficient to establish the stability profile
of the drug. For drug with proposed shelf life of at least 12 months, the frequency of testing at
long term storage condition should normally be every 6 months over first year, and the second
year and annually thereafter through the proposed re-test period or shelf life.
• At the accelerated storage condition, a minimum of three time points including the initial and
final time points (e.g., 0, 3 and 6 months) from a 6 months study is recommended.
• Reduced designs i.e., matrixing or bracketing, where the testing frequency is reduced or
certain factor combinations are not tested at all, can be applied if justified.
Storage condition
The world can be divided in to four climatic
zones I - IV. This guideline address zone IV.

18. • The purpose of stability is to establish, based on testing a minimum of at least three batches of the drug, a retest period
applicable to all future batches for the drug substance, or a shelf life and label storage instructions applicable for all
future batches of the drug product manufactured and packed under similar circumstances.
• An Ayurvedic drug can be considered to be stable if “no significant change” occurs during at any time of testing at
accelerated storage condition or at real time storage condition.
• “Significant change” for a drug is defined as :
• A + or – 20% change from the initial assay value (If the drug is analyzed for its marker).
• A + or – 15% change from the initial assay value (If the drug is analyzed for its active compound).
• Appearance of new spots in Identification by TLC (when compared with the sample stored in less than 10 Degree) or
completely disappearance of existing spot.
• The physico-chemical parameters (moisture, ash, particle size) shall not vary beyond 25% of the initial value.
• Failure to meet the acceptance criteria as per individual monographs or specification.
• Failure to meet acceptance criteria for appearance (Physical attributes, and functionality tests e.g., color, phase
separation, caking, hardness).
Evaluation

19. References
• https://www.researchgate.net/publication/256294821_Shelf_life_of_Ayurvedic_dosage_forms_-
_Traditional_view_current_status_and_prospective_need
• http://www.iamj.in/posts/2019/images/upload/79_86.pdf
• http://www.iamj.in/prposts/2019/images/upload/1548_1556.pdf
• http://nopr.niscair.res.in/bitstream/123456789/12821/4/IJTK%2010%284%29%20672-677.pdf
• https://www.researchgate.net/publication/345156964_Concept_of_Stability_Study_of_Churna_Kalpana
• https://www.researchgate.net/publication/342149464_Shelf_Life_Evaluation_of_Shirishavaleha_and_its_
Granules_A_Preliminary_Study
• https://www.slideshare.net/HariaumshreeNair/saviryata-avadhi-shelf-life-in-ayurveda-and-modern-point-
of-view
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728871/
• https://www.ayush.gov.in/docs/guideline-drug-development.pdf
• https://main.ayush.gov.in/sites/default/files/Ayurvedic%20Pharmacopoeia%20of%20India%20part%201%2
0volume%20IX.pdf
• https://niti.gov.in/planningcommission.gov.in/docs/plans/annualplan/ap2021pdf/ap2021ch5-4-2.pdf

20. Thank You!!