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Vitamin A
44.0
Vitamin C
23.0
Vitamin B12
7.7
Folic acid
10.5
Source: Berry Ottaway & Associates Ltd., UK, private communication, 1991
Temperature
Moisture
Oxygen
Light
The first four of the above list apply to almost every product containing organic (in the chemical
sense) active ingredients. Products containing only inorganic mineral salts (such as calcium
chloride) tend to be stable.
When formulating a supplement product it is recommended that a critical evaluation of the
proposed formulation is carried out in order to minimise the degradative effects of the factors
listed above, both singly and in combination.
It is also important that the form and composition of the packaging is selected to provide a good
barrier to moisture, oxygen and light. The importance of the various factors affecting shelf-life is
discussed below:
2.1.Chemical Stability:
Different ingredients and supplements have differing degrees of inherent chemical
stability, depending on their chemical composition. Some kinds of molecules are
very stable; they do not easily react with other molecules and will remain unchanged
over long periods of time. For example, minerals such as silica or magnesium
phosphate are quite stable, especially if kept away from moisture, and can remain
unchanged over decades or longer. These types of molecules are often described as
inert.
On the other hand, some kinds of molecules are less stable and react relatively
quickly with other molecules to form degradation products. For example, unsaturated
fatty acids such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)
may oxidise over the course of a few months (or even less) when exposed to oxygen,
especially if heat and/or light is present. These types of molecules may be described
as labile or reactive.
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It is also possible to make some generalisations about ways to maintain a supplements required
shelf-life. These include:
Use of lower storage temperatures such as refrigeration (for example, at 03C), particularly for liquid products.
Reducing the number of doses per container, so as to reduce the in-use period. It
should be noted that it will often be necessary to reduce not only the number of
doses per container but also the overall container size, in order to achieve the
intended effect of improving the supplements stability.
It is recommended that consideration is given to the suitability of the packaging before a product
stability study is undertaken.
The accuracy of both real-time and accelerated shelf-life studies depends on the selection of
representative product ingredients or constituents, or specific product attributes, that can be
examined qualitatively or tested quantitatively in relation to the product matrix.
Well-characterised quantitative test methods are available from the literature and various
compendia for all the vitamins and many other supplement ingredients (see Appendix II). For
botanical products that do not declare specific levels of naturally-occurring constituents, a
qualitative review of organoleptic attributes of taste, odour and colour may be appropriate to
review product stability. In the case when a botanical constituent is declared on the label, a
significant amount of analytical work may be needed on the product before a stability study can
commence, unless a scientifically valid method is available for quantifying the level of the
constituent.
For products containing two or more ingredients, different ingredients may degrade at different
rates, so reliance cannot necessarily be placed on one single ingredient or constituent; instead
multiple assays may be needed.
As already indicated, it is recommended that accelerated stability studies alone do not serve as
the sole basis for estimating a products shelf-life. For products containing multiple ingredients, a
single accelerated study provides an approximation of the shelf-life and it should be supported by
real-time studies. Other data can consist of real-time experience on similar products or other
information on the stability of the ingredients and constituents.
The shelf-life specifications should be documented for each ingredient or supplement. This
should include a list of the tests to be performed, test methods to be used and acceptance criteria
required for that ingredient or supplement. The group of tests and the criteria for each test result
that are used for the shelf-life specification may be different to the tests and criteria for each test
result used for initial release of the product at the time of manufacture. This is particularly the
case if known changes are expected to occur during storage.
There are a variety of types of tests and examinations which may be relevant to establish shelflife of the finished product:
4.1 Organoleptic Testing:
Organoleptic stability tests compare the general appearance, colour, odour, taste
and/or texture of aged product to those of freshly-made product. These tests are
useful to evaluate whether the stored product will continue to be acceptable for use in
production and/or to the consumer. With well trained and experienced evaluators,
organoleptic stability testing is often able to discern more subtle changes than many
quantitative chemical tests. Organoleptic stability testing has the advantage of
examining the product in its entirety, which especially for chemically complex
materials such as botanicals may provide a more reliable evaluation of product
quality and stability than quantification of merely one or a few marker compounds
can reveal.
4.2 Physical Attributes: Many physical characteristics play an important role in product
quality and may be appropriate to monitor for changes during product storage.
a. Significant changes during storage, in moisture content, loss on drying,
water activity, and/or average dosage weight may affect the stability of the
product. Where such changes are observed, further testing of chemical or
microbiological attributes may be appropriate.
b. Disintegration and/or dissolution of tablets and capsules may change over
time and may be appropriate to monitor during a shelf-life study.
c. Tablets and capsules may be monitored for changes in friability, hardness
and/or seal integrity, as applicable to the product.
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Quantitative chemical tests may also be important for other ingredients such as
microbial preservatives, antioxidants or known degradation products. In addition, the
content of known components in the formula may be monitored as a guide to the
products stability, even when no quantitative label claims for those components are
made on the product label.
4.5 Chemical Fingerprints:
So called fingerprints such as those produced from thin layer or high performance
thin layer chromatography (TLC or HPTLC), high pressure liquid chromatography
(HPLC), Fourier-Transform infrared spectroscopy (FTIR), or other spectroscopic
analysis of complex materials, can give a useful representation of a products
chemical composition, particularly for products containing botanical ingredients, and
may be indicative of product stability.
Criteria may be established to determine how much change in a fingerprint is
acceptable, such as the number of bands which may appear or disappear in a
chromatographic fingerprint, or the amount of change allowed in the size or intensity
of a peak. Fingerprints provide a broad view of a chemically complex material and
may thereby yield more reliable and sensitive stability data than quantitative testing
of one or a few marker compounds. To facilitate comparison of chromatograms,
software such as Computer Aided Similarity Evaluation (CASE) has been developed.
4.6 Bioassays:
Occasionally, where appropriate, the biological activity of an ingredient or
supplement may be evaluated. This type of test is typically conducted in vitro, i.e. in
a culture of tissue, cells, or microorganisms, although it may also be conducted in
vivo, i.e. in a living organism. Bioassays can be used to examine the effect of
ingredients or supplements on macrophage activation, cytokine production, receptor
binding, etc. Bioassays can be especially useful where it is known that a chemically
complex ingredient or supplement produces a certain biological effect, but it is not
known precisely which component(s) of the material are responsible for the effect.
4.7 Impurity Tests:
In general, it is not necessary for a shelf-life specification to include tests for
impurities such as heavy metals or pesticides, since these should not change so long
as the product is stored properly.
However, there are some impurities whose content may change during storage and
which may therefore be appropriate to be include in the shelf-life study. For example,
mycotoxin levels may increase during storage if elevated fungal counts are observed.
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4) Packaging:
The material used for shelf-life testing or studies should be packaged in the same
manner as is intended for the commercial storage and distribution of the ingredient or
product (including the primary container closure system, the amount of fill and
headspace inside the container, the label, and any secondary packaging). If this is not
possible, the samples should be packaged using at least the same materials of
construction as the commercial material is packaged in (for example, brown glass,
high-density polyethylene etc.), and should be proportionately similar in terms of fill
level and headspace or appropriately bracketed as described in section 8 below.
5) Sampling:
The size and nature of samples to be taken from each batch should be carefully
considered. Where study samples are all taken at the beginning of the study, the
quantity must be sufficient to allow completion of all required testing over the course
of as many time points as will be tested. On the other hand, where study samples are
taken from existing inventory at various time points, the quantity collected need be
sufficient only for testing at the given time.
In general, stability samples should be taken using proper sampling procedures to
ensure the material collected is properly representative of the whole batch at the time
of manufacture or receipt. However, in cases where samples from existing
commercial stock are taken for shelf-life testing, it may be appropriate to select
samples from worst case conditions such as the warmest location in the warehouse.
The provenance of each sample used in the shelf-life study should be carefully
documented in case questions arise. This may include data such as the date of the
sampling, the person who took the sample, the sampling SOP(s) used, the total size
and number of containers in the batch at the time of sampling, the warehouse or other
storage location(s) sampled (where applicable), the number and identity of batch
containers from which sample portions were taken, the total size and number of
containers in the sample, and whether the final sample represents a composite or
single sample. Supplement manufacturers may find it useful to assign a unique
identification number to each unique sample taken.
6) Sample Storage Conditions:
Where shelf-life samples are taken at one point in time and then stored for an
extended period prior to analysis, careful consideration should be given to the
conditions under which the samples will be stored. The chosen storage conditions
should, at a minimum, be monitored and documented throughout the storage period;
many companies go further and actively control the storage conditions, for example
by use of environmental chambers which keep the storage environment within strict
ranges of temperature and humidity.
For real-time testing, the samples should be stored under conditions as similar as
possible to those experienced by the product in commercial storage. Most commonly,
this means storage at room temperature, i.e. around 25C, and humidity between 3070% RH. However, it may be appropriate to conduct long-term testing at 30C 2C
/ 65% RH 5% RH. This may be warranted where there are large climatic variations
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Different container sizes and/or fills in the same container closure system.
Matrixing should generally not be performed across different test attributes or across
different storage conditions.
The matrixing design should be as balanced as possible so that each combination of
factors is tested equally over the duration of the study. All selected factor
combinations are usually tested at the initial and final time points, while only a
subset of the combinations is tested at each intermediate time point.
Due to the reduced amount of data collected, a matrixing shelf-life study has less
precision and yields a shorter shelf-life than the corresponding full study.
Furthermore, use of a matrixing design should be limited to where experience or
other information indicates that the shelf-life of the product is predictable. If there is
uncertainty or variability, a full study is generally preferable.
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Annex I
Glossary of Terms
Batch
See Lot.
Finished product
Labile constituent
Light transmittance
The ratio of the intensity of the light that has passed through a
substance to the intensity of the light when it entered the
substance.
Lot
Manufacture
Manufacturer
Overage
Packaging
Packaging material
Permeation rate
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Stability
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Appendix II
Resources
Chemical deterioration and physical instability of food and beverages. Ed. Leif Skibsted, Jens
Risbo and Mogens Andersen. Woodhead Publishing, UK. 2010. ISBN 1 84569 495 3, ISBN-13:
978 1 84569 495 1
Food and beverage stability and shelf life Ed. David Kilcast. Woodhead Publishing, UK. 2011.
ISBN 1 84569 701 4, ISBN-13: 978 1 84569 701 3
Fundamentals in food chemistry. Ed. Bimlesh Mann. Woodhead Publishing India. 2012. ISBN10: 0857091069, ISBN-13: 978 085709 106 2
Global Guide to Good Manufacturing Practice for Supplements. International Alliance of
Dietary / Food Supplement Associations, Belgium. 2011. www.iadsa.org
Oxidation in foods and beverages and antioxidant applications Volume 1: Understanding
mechanisms of oxidation and antioxidant activity. Ed. E Decker. 2010. ISBN: 978 1 84569 648
1
Oxidation in foods and beverages and antioxidant applications Volume2: Management in
different industry sectors. Ed. E Decker. 2010. ISBN: 978 1 84569 983 3
Shelf Life Dating of Botanical Supplement Ingredients and Products.
Staci, Managing Editor. The American Herbal Products Association, USA. 2011. www.ahpa.org
Stability testing guideline for dietary supplements. NSF International, USA. 2011. www.nsf.org
The stability of vitamins in fortified foods and supplements. Berry Ottaway P. In Food
Fortification and Supplementation Ed. Peter Berry Ottaway. CRC Press Ltd., USA. 2008. ISBN
978 1 42007 201 3
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