fundamentals of stability testing

Review paper Fundamentals of stability testing

JOHN S. CANNELL, Warner-Lambert (UK) Ltd., Eastleigh Operations Division, Eastleigh. Hampshire SO5 320, UK

Presented to The Svciet-v of Cosmetic Chemists’ Symposium on ‘Prodirct Stability’, S 4 November, IY84 it1 Coventry, U K

Key words: Stability, product-container compatibility. release specification, check specification. shelf-life, accelerated tests.

Synopsis The principles on which stability tests are based are reviewed. The need to differentiate between product stability and product-container compatibility is emphasized. Recognition of this distinction is fundamental to the efficient organisation and execution of stability tests.

Attention is also drawn to the desirability of having for every product a release specification with which it must comply when manufactured and a broader check specification with which it must comply throughout its shelf-life.

Test methods and the interpretation of the data accrued throughout a test are also discussed.

I t is concluded that stability tests should not be conducted in accordance with a stan- dardized routine pattern but that the objectives of each test should be detined and thc test designed to achieve those objectives in the most efficient way.

Ides regles fondamentales des essais de stabilite

RCsumP On passe en revue les regles fondamentales des essais de stabilite-en soulignant la neccssite de differencier la stabiliti intrinseque du produit de la compatibilite contenant- contenu. La reconnaissance dc cette distinction est fondamentale pour I’organisation et I’execution efficace des essais de stabilite.

II est souhaitable d’avoir pour chaque produit un cahier des charges tres strict. qui devra etre respecte au moment de la fabrication, et des sdcifications plus larges qui s’appli- queront pendant la durCe de vie du produit.

On discute la methodologie des essais et I’interpretation des resultats. Les essais de stabilite ne doivent pas Ctre effectues selon une procedure de routine mais

chaque essai doit Ctre conduit de fagon A atteindre les objectifs definis de la maniere la plus efficace.

INTRODUCTION

The gencral objective o f a stability test is to determine whether a given product in the container in which it is t o be marketed has an adequate shelf-life under the conditions of the market in which it is to be sold. The term ‘shelf-life’ merits closer consideration.

Definitions There is no definition of shelf-life in either the EEC Cosmetics Directives or the UK Cosmetic Products (Safety) Regulations 1984. T h e first Directive requires (Article 6) that cosmetic

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products should be labelled with ‘the expiry date of products with a stability of less than three years,’ but does not elaborate o n this.

The Cosmetic Products (Safety) Regulations 1984 require [Regulatione 8(l)(b)] that ‘I cosmetic product likely within 30 months from the date of manufacture thereof to cease to comply with the requirements of Regulation 5 above or to fulfill the purpose far which it was intended’ shall carry on the label the earliest date on which it is likely 80 to cease. Regulation 5 requires that ‘a cosmetic product shall not be liable to cause damage to human health when it is applied under normal conditions of use’. This refers to only one of the aspects of a cosmetic product that may set a limit to the shelf-life of a product and is in no sense B definition of shelf- life as such, but it is as near as the Regulations come to such a definition.

A practical definition of shelf-life may be: ‘That period of time during which a product re- mains in compliance with its specification when stored under the conditions of the market’. From this follows the question of specifications. Every product undergoes change as it ages and sooner or later becomes unsatisfactory, by which is meant in this context that it no longer con- forms to its specification. If a batch of a product is close to the spedfication limit in respect of any parameter at the time of manufacture then even slight change may mean that it no longer complies with its specification, so that its effective shelf-life is very short. For this reason it is desirable to have two specifications:

- the release specification with which a product must comply at the time of manufacture; - the check specifcation with which the product must comply throughout its shelf-life.

The use of release and check specifications is a normal practice in the pharmaceutical industry. To those in the cosmetic industry who have not already adopted the use of these two specifications the practice is to be commended.

The release specification has narrower limits than the check specification. The shelf-life is that period of time in which a product stored under market conditions changes from the limit of the release specification to the limit of the check specification in respect of any specified parameter. This is illustrated diagramatically in Figure 1. In the example shown the least stable parameter has a release specification of 2 5% of the nominal value and a check specification of +. 10% of the nominal value. The period which elapses until the product at the limit of the release specification at the time of manufacture changes until it has reached the limit of the check specification, is the minimum shelf-life; the product which is close to the nominal value or the time of manufacture will continue to comply with the check specification for longer than this.

It should be noted that it is not always the lower limits of the specification that are involved; ingredients that undergo decomposition do obviously fall but other parameters, such as total solids content, rise as the product ages if the container is permeable to water vapour.

Shelf-life relates to the stability not only of the product but also to the combination of product and its immediate container. That is, it embraces not only the chemical and physical stability of the product but also possible interactions between the product and the container which may have adverse effects on either product or container or both. The terms ‘product stability’ and ‘product-container compatibility’ may be defined as follows.

- Product stubifity is the stability of the product stored in an inert, impermeable container with which it does not interact and which fully protects it from the ambient atmosphere.

- Product-container compatibility includes all possible interactions between product and container such as absorption of constituents of the product by the container, leaching of constituents of the container by the product, corrosion or other adverse effects of the

Stability testing 293

I I I I I I I I I I I

R e l e a s e svec.

Shelf - l i f e I I

C h e c k spec.

L T i m e

Figure 1. Release and check specifications as determinants of shelf-life. The shelf-life is that period of time during which the value of the least stable parameter changes from the limiting value of the release specification to the limiting value of the check specification.

product on the container and the barrier properties of the container; that is, its effectiveness in protecting the product from the adverse effects of atmospheric oxygen and/or water vapour and in retaining water and other volatile constituents of the product.

Hence, while both product stability and product-container compatibility together constitute the total overall stability of the product to be marketed, they are also quite distinct and separate concepts. It is suggested that recognition of this distinction is fundamental to the efficient and cconornical design and execution of stability tests.

Objectives Also fundamental to the proper design of a test is clear definition of the objectives of the test. For example, a test may have one or more of the following objectives: - assessment of product stability; - assessment of product/container compatibility;

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- comparison of the stability of a product made to a modified formula or by a modified

- comparison of compatibility of a product with a new container with that with original

This list could be continued. Only if the objectives are clearly defined can the test be economi- cally designed.

method with that of the original product;

container.

Principles Test procedures are designed to provide the desired information in the shortest possible time. To achieve this, samples are kept under conditions designed to accelerate any changes occurring at ‘normal’ conditions.

Experience shows that the greater the degree of acceleration that a test attempts to achieve, ie, the further removed are the conditions of test from actual market conditions, the greater is the risk of occurrence of changes which never occur at market conditions, ie. the test no longer merely accelerates changes occurring under ‘normal’ conditions.

In order to bring about this desired acceleration, samples are subjected to the following.

Elevated temperatures A general approximation is that a 10°C rise in temperature doubles the rate of reaction, but in practice, the usefulness of this approximation is limited by the fact that at temperature far removed from ‘normal’, other changes often take place which never occur at normal temperatures. Nevertheless, storage of samples at very high temperatures can be useful. It can be a valuable indicator of stability, but not of instability.

Thus, a product that shows good chemical stability at 70-80”C is certain to be very stable (chemically, but not necessarily physically), at ‘normal’ temperatures. Suggested test storage temperatures are discussed later.

Elevated humidities Tests at elevated humidities are normally tests of the pack and not of the product. They serve either to show the effect, if any, of storage at elevated humidities on the container andor as a measure of the barrier properties of the container.

Products may be adversely affected by exposure to atmospheric humidity but if this happens in the product in its sales pack, it indicates that the pack provides inadequate protection from the atmosphere.

Tests at elevated humidities are even less certain only to accelerate changes at ‘normal’ storage conditions, than are tests at elevated temperatures. If the hazard is ingress of water vapour, elevated humidities do, within limits, accelerate; if the hazard is loss of water or other volatile constituents, elevated humidities may retard changes occurring at ‘normal’ conditions.

Cycling tests Tests in which the temperature and/or humidity are changed at regular intervals and which, therefore, subject the pack to varying stresses, are sometimes more severe tests than continuous storage at one condition. They can be of particular value in assessing internal lacquers in aluminium tubes.

Stubility testing 295

Freezeelthuw tests Such tests are applicable to:

- liquid products as a measure of liability to crystallize, deposit or cloud; - emulsions and creams as an indicator of emulsion stability.

Exposure to light The effects of exposure to light are difficult to accelerate in the laboratory. The source of illumination should ideally have the same spectral distribution as daylight; most artificial light sources d o not, although xenon discharge lamps do. In practice, it is useful to expose test samples to daylight (not direct sunlight) and also to expose continuously to a battery of fluorescent tubes.

Experience shows that it is often difficult to assess the extent of exposure t o light that samples receive in the market and hence to estimate the degree of exaggeration or acceleration that any one test gives. Thus the interpretation of test results can be difficult.

Mechanical tests Vibration tests, for example, may be needed in such situations as the following:

- to determine whether classification (demixing) of powders or granular products is liable to

- to establish that emulsions d o not break or foams collapse. occur;

Test conditions Standard conditions

4"Clambient humidity. This is mainly useful for control purposes since chemical (but not necessarily physical) changes are minimal.

2O"Celambient humidity. Since ambient temperature and humidity are subject to considerable variation, both seasonal and diurnal, it is greatly preferable to store samples at a controlled constant temperature (20°C) rather than 'room temperature'. If this is done samples stored at elevated temperatures represent a more constant degree of acceleration and render stability predictions based on them being more accurate. 37"Clambient humidity; 45YYambient humidity; 37"C/80% r.h.

Non-standard conditions 60, 70 or 80°C--storage under these conditions can in appropriate instances provide convincing evidence of stability (see above). Tests at very high temperatures need be, and should be, continued for only a short period, ic, days or a few weeks rather than months.

Other specific temperatures and humidities Storage of samples a t the 'standard conditions' normally gives evidence on which a prediction can be made with reasonable accuracy of the stabilitylcompatibility and shelf-life of the product in domestic market conditions. Where a product is to be marketed in export markets which have high temperatures and/or high humidities, or both, prediction of shelf-life is more difficult.

The effects of high temperature and high humidity are often inter-related and while it is possible to accelerate temperature effects by storage at still higher temperatures it is not possible to d o this with humidities that are already high. For this reason it is always advisable in

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such cases t o store samples under actual market conditions. Information on climatic conditions in different parts of the world is available in published data. It is recommended that samples be stored at mean maximum temperature and mean maximum humidity appropriate t o the market concerned. Thus, when it is intended t o export a product t o a number of different countries it may, and often will be, necessary t o carry out separate tests a t several different conditions of temperature and humidity. Climatic conditions in all the intended markets should be considered.

It will normally be possible to span all of those market conditions by the proper selection of a small number of test conditions. A product may well have a different shelf-life in different markets; alternatively, a product may be released for marketing in certain markets but not in others.

While the climatic conditions in any given market can readily be found from published data, the temperature and humidity conditions t o which a product may be subjected during shipment to that market are largely unknown; they may be very severe and potentially damaging. The temperatures in the holds of ships in the tropics can be very high and goods standing at the dockside in tropical ports may be subjected t o very high temperatures. Hence, their journey to the market may be more damaging than actual conditions in that market. It is worthwhile to attempt t o form some estimate of the hazard by means of transport tests in which products are shipped by the route in question and returned for examination. If storage is at the mean maximum temperature and humidity, this will give some exaggeration of actual market conditions, the extent of which will depend on diurnal and seasonal variations occurring in the market in question.

Cycling tests Tests under conditions which are periodically changed can, by imposing changing stresses on a pack, reveal inadequacies more quickly than can storage at a constant temperature. For example, it may be in some cases a more rigorous test to cycle 24 hourly at 45°C and room temperature than to store continuously at 45°C.

Similarly, in tests of water-vapour barrier properties of packs, changing conditions of temperature and humidity sometimes reveal inadequacies that continuous storage a t one equili- brium condition does not. The actual conditions between which packs are cycled will depend on the conditions likely to be encountered in the market. Suggested conditions for such tests are: are:

- 37"C/80% r.h. - R.T./ambient humidity; - mean maximum temperaturehean maximum humidity - R.T./ambient humidity in each

case alternating 24 hourly.

Freezelthaw tests Freeze/thaw (minus 30"CIR.T.) tests should be carried out on all solutions, emulsions, creams and all other liquid or semi-solid products. A suggested minimum number of cycles is six. These tests provide evidence of emulsion stability, tendency to crystallization, deposition o r clouding, and, if these happen, whether they are spontaneously reversible. Changes that d o not revert, eg, emulsion separation, d o not necessarily eliminate a product. Control products should always be used.


Exposure to light Light can bring about changes in products, and products that are likely to be exposed to light in the market should always be tested by exposure to light. Recommended test conditions are:

- north-facing daylight. Exposure to direct sunlight is generally to be avoided since products are seldom exposed to it, and because it can quickly produce effects that are never seen in practice;

- continuous exposure in a light testing cabinet. Such a cabinet may contain a battery of fluorescent tubes, and samples should be held about one foot away from it. One tube suitable for this purpose is Polarite-daylight type, 40w (Thorn-EMI). The tubes are 132 cm in length and a battery of 12 such tubes provides suitable illumination.

Mechanical tests Vibration tests on a suitable vibrator for a period of some hours should be carried out in appropriate instances. It is preferable to treat different samples with different frequencies and amplitudes of vibration. Emulsions may be centrifuged as a means of assessing stability.

Test samples It is suggested that stability testing should be a continuing process involving samples from each stage of the development of a product. It is seldom worthwhile or even practicable to submit to a formal test programme small quantities of products produced by formulation chemists in de- veloping a new formula. However, it can often be very useful for the formulation chemist to carry out some ad hoc tests on certain aspects of the stability of hidher formulation. A few samples can, with advantage, be put on test to assess those aspects which the development chemist recognizes as being the most likely to give problems. Such tests are always considerably ahead in time of tests on pilot batches. They can give early warning of stability problems and enable the corrective action to be taken at an early stage and thus save time and development resource. It can be advantageous to put each formula on a stability test and to leave earlicr formulae on storage when later different formulae are developed; the earlier formula may eventually prove to be more stable than later formulae.

Pilot batches I t is suggested that samples from at least two pilot batches should be put on a full formal stability test. It is desirable, as far as is practicable, that the different pilot batches should be made with different lots of raw materials.

Production batches While it is essential to study the stability of pilot batches, it is also imperative that the stability of production scale batches also be studied. The different scales of manufacture can give products which behave differently on stability test. The first two production batches should be put on a full stability test programme at elevated temperatures and, if appropriate, a t elevated humidities. The samples at room temperature are kept on tcst for the projected shelf-life of the product.

When a product is in regular production, however, there may be, with the passage of time, unsuspected and undetected changes in raw materials, methods of product handling or some

298 J . S. Cannell

other change that can affect the stability of the product. For this reason it is desirable that there should be a continuing programme of tests of the stability of all products in regular production.

It is highly desirable that from every product in regular production samples be withdrawn periodically and put on long term stability test. In such tests samples should be stored only at room temperature (or in the case of samples for export markets at the conditions of the market). Examinations need to be carried out only at infrequent intervals.

Stability tests on pilot batches and on first production batches are carried out not only in the case of new products but also where there has been any change in the formulation of the product or in the source of the raw materials used or in the equipment used in manufacture or filling or in the method of manufacture or filling.

Tests must always be carried out in the pack in which the product is to be marketed. Such tests embrace both product stability and product-container compatibility. At the same time the stability of the product must also be studied by the storage of the product in inert tightly closed containers (see controls below).

In product-container compatibility tests the product to be tested is the pack in the immediate container in which it is to be marketed. All sizes of the pack to be marketed should be included in the test. Before starting a product-container compatibility test it is essential to ensure that a complete detailed specification for the primary container concerned has been received. When samples are removed for examination, the remaining product in an unopened container should be destroyed and a fresh unopened container used for each subsequent examination. In the case of bulk packages from which the product is likely to be removed in successive quantities over a period of time, separate tests should be carried out to assess the effect of storage in partly filled containers. These are additional to the above tests. When the product is packed in a container with a screw cap the cap should always be applied to a pre-determined and measured torque. The release torque should be measured at the beginning of the test, and whenever a container is opened throughout the whole period of the test.

Controls Wherever possible, a control product andor pack should always be included in every test. In stability tests, this may not always be possible; in many instances, however, a related or a com- petitive product of a similar type which is known to, or can be presumed to, exhibit satisfactory stability under market conditions, can often be included and can provide valuable help in the evaluation of the test data.

In tests of products in sales packs, there should always be included in the test control samples of the product packaged in inert impermeable containers. Without such controls it is not possible to know with certainty whether any changes observed in the product are the results of incompatibility with, or inadequacy of, the package, or are due to the inherent instability of products.

In tests on products made to a modified formula or by a modified process, or in tests on new packages, the original product or package should invariably be used as a control.

Examination schedules

Product - Many of the important properties of products, and particularly cosmetic products, are

assessed subjectively, eg, appearance, colour, odour, taste, texture, and cannot readily be ex-


pressed in numerical terms. Record keeping and the evaluation of results are facilitated if instead of a subjective description, any changes are recorded in terms of a scale such as the following:

barely discernible; slight; distinct; marked; very marked.

- All the parameters of product specifications should be measured, although not necessarily every one at every examination. But product specifications and test methods that are satisfactory for the routine quality control of production are not necessarily adequate for the investigation of stability; therefore, other parameters which are not a part of the specification should also be measured wherever this is appropriate.

- Where the product contains an active ingredient possible mechanisms of degradation of thc ingredient should be considered and investigated, eg, decomposition of the active ingredient or interaction of the active ingredient with other compounds present. Analytical methods used for the determination of ingredients should be stability indicating - ie, they must differentiate between the active ingredient and possible decomposition or degradation products. Tests to confirm that the analytical methods used in stability testing are in fact stability- indicating should be conducted.

- The most probable effect of exposure t o light is a change of colour, but this is not necessarily the only or even the most important effect. Some compounds are photo-labile; therefore, samples that have been cxposed to light should be examined in full and not only in terms of their colour.

- Emulsions should be examined after storage for droplet size of the disperse phase even if this is not included in the product specification.

- Challenge tests should always be carried out on stored samples before stability clearance is given in order to ensure that the product continues to have an effective preservative system. Some preservatives are inactivated by non-ionic surface-active agents, others tend to be absorbed by plastic containers and so removed from the product, while others may undergo dcgradation.

- Preservatives should also be assayed throughout the test. It is not always sufficient to rely on challenge tests only. The degradation products of some antimicrobials may themselves have considerable antimicrobial activity, eg, thiomersal.

The British Pharmacopoeia 1980 describes a test for “Effectiveness of Antimicrobial Preserva- tives in Pharmaceutical Products’ (Appendix XVI C , p. A192). This describes test procedures and specifies levels of antimicrobial efficacy for different types of pharmaceutical products. The product must also comply with this test at the end of its shelf-life. The same test procedure and standards of antimicrobial activity can usefully be applied to cosmetic products.

Pack Except for non-volatile, non-absorbent products, weight loss (or gain) measurements should always be made in order to confirm the adequacy of the pack to retain the product without loss by evaporation of volatile constituents or to protect it from atmospheric moisture, oxygen or carbon dioxide. The package itself should be carefully examined for change during storage, eg,

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stress-cracking of plastic tubes, blistering and/or detachment of internal lacquer on cans and tubes, blockage of spray valves, etc., and label adhesion. As mentioned above, some ingredients, including some preservatives, are absorbed by plastic from solution; evidence of such absorption should be sought. Changes in the container (as well as the product) of any sort in package should be looked for and reported.

It is not possible to prescribe a single examination schedule which is appropriate for all products and all situations. Examination schedules for each product andlor package should be determined in the light of what is appropriate in each instance.

Examinations are most frequent in the early part of the test and on the samples stored at elevated temperatures. Before starting a test it is necessary to draw up a projected examination schedule and to put on storage at each test condition more than sufficient samples to meet that schedule. The examination schedule drawn up at the beginning of the test may need to be modified in the light of findings in the earlier stages of the test. Thus. if changes appear at an early stage it may be necessary to carry out more frequent testing; alternatively, the reverse situation may apply. There must also be enough samples put on test to allow for duplicate examinations and for the proper investigation of special problems.

Duration of tests The duration of tests at any one condition depends on the condition and again must be subject to variation in the light of findings as the test progresses. The following are suggested durations at different conditions:

4"c lfor the projected shelf-life of the product; R.T. 37°C - 3-6 months maximum; 45°C - 1-3 months maximum; 37"C/80% r.h. - 1 month maximum; light tests - up to a maximum of 1 month.

Tropical market conditions. Since storage at mean maximum temperature and mean maximum humidity may give little acceleration over market conditions, these should be continued for thc projected shelf-life of the product.

Recording of results A stability test involves the accumulation of a substantial amount of data over a prolonged period of time and may require the production of reports at several stages of the test. This is a situation which lends itself well to the use of a micro-computer or word processor.

Interpretation The ease or otherwise with which test data are interpreted and related to behaviour in the market depends on the type of test. Tests which are essentially 'comparison' tests are relatively easy to assess. In such tests there is always a control product or pack, the behaviour of which under market conditions is known. In such instances, interpretation of test data becomes a matter of deciding whether the test product or pack is better than, equal to or inferior to the control. It is not usually necessary to attempt to reproduce the conditions of a particular market. The evaluation and assessment of test data on completely new products or packs and the problem of deciding whether they are sufficiently stable or whether they adequately protect


the product under market conditions is more difficult. The difficulty is the greater in relation to overseas markets having temperatures and humidities higher than those of the UK. The stability of the product and shelf-life of the product in its sales pack are considered separately below.

Product stability Product stability is, by definition, the inherent stability of the product independent of possible interactions with the immediate container or of questions of the adequacy or otherwise of the protection afforded by the sales packagc. Therefore, in assessing product stability, only data on samples stored in inert, highly protective packs, need, or should be, taken into account. Changes in samples stored at elevated temperatures represent acceleration of changes occurring at room temperature. The degree of acceleration can be assessed by comparing the extent of the changes occurring at 37°C and 45°C and at other elevated temperatures with those occurring in samples stored at room temperature (20°C).

Assessment of samples stored at elevated temperature may bc made very approximately on the assumption of a two-fold acceleration for each 10°C rise in temperature. Even at best this is a rather crude approximation. In appropriate instances the Arrhenius equation may be applied to the evaluation of assay data in stability tests and to the prediction of shelf-life.

Where k = specific reaction rate; A =frequency factor; Ea = energy of activation; K = gas constant; T = absolute temperature.

The usefulness of the Arrhenius .equation in establishing the shelf-life of cosmetic products is, however, limited by the fact that it is valid only for homogeneous liquid systems which excludes a high proportion of cosmetic products. Furthermore. many critical properties of cosmetics, including those which may limit shelf-life, are assessed subjectively (eg, odour, colour, texture, etc.) and are not capable of being treated mathematically.

An estimate of the degree of acceleration over market conditions can be made only if the mean temperature in the market is known. For UK domestic conditions this presents little problem since the 20°C (R.T.) condition is very close to normal temperatures in the UK market. Hence, storage at 45°C for 3 months may, but not necessarily always does, represent 12-18 months at room temperature.

In markets having higher temperatures than the UK, the 37°C and 45°C conditions are less far removed from market conditions. Hence, storage at 37°C or 45°C represents correspondingly less acceleration over conditions to which the product is likely to be exposed in the market. Therefore, before a conclusion is reached, tests must be continued for a sufficiently long time to demonstrate an adequate shelf-life in the market concerned.

Productlconrainer compatibility Tests on products packaged in market packages involve samples stored at elevated humidities as well as those stored at elevated temperatures. The effect of such storage may be on either the package or the product or both and these effects may be classified as follows.

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- Effects of storage environment on package eg, loosening of cap wads, failure of label adhesive and exfoliation of laminates.

- Effects of product from inadequate barrier properties of package. Such effects are shown by differences between the test samples and the control samples stored in impermeable containers eg, (a) adverse effects on moisture sensitive products resulting from the inward passage of water-vapour; or on certain products because of the inward diffusion of atmospheric oxygen; (b) adverse effects arising from the outward passage of volatile constituents of product, eg, water vapour, ie, evaporation of product; loss of perfume or flavour. Samples submitted to low pressures while being airfreighted have been known to suffer perfume loss.

- Effects of incompatibility between product and this primary container which may be on either product or package or both eg, corrosion of metal tubes; stress-cracking of plastic tubes; absorption of constituents of the product such as preservatives by the container; leaching of constituents of the container by the product.

The evaluation of test results and the establishment of a shelf-life under any given market conditions requires a knowledge of the extent of acceleration that the test conditions represent in relation to market conditions. Such considerations in relation to temperature alone have been considered in an earlier section. Tests at elevated temperatures and elevated humidities are more difficult to accelerate and interpret. Since normal ambient conditions in the UK have fairly high humidity, storage at R.T. (20°C) and 80% r. h. may represent little or no acceleration over normal domestic conditions.

At 37"C/80% r.h. the atmosphere contains very much more water vapour than does air at 20°c/80% r.h. In assessi.ig the water vapour bamer properties of a container at 37"c/80°/0 r.h. this may represent an acceleration of 8-10-fold over 2OoC/80% r.h. (Based on the vapour pressure of water at 37°C and 20°C respectively and assuming a doubling of the rate of diffusion of water vapour per 10°C rise in temperature).

In relation to climatic conditions in many other markets 37"U80% r.h. (which is the most severe high humidity test condition generally proposed on the basis of experience) represents less acceleration and may be continued for correspondingly longer.

In view of the difficulty of satisfactorily exaggerating conditions in high humidity markets, it is always desirable to put samples on test at actual conditions of the market or markets in which the product is to be sold, ie, storage at the mean maximum temperature and mean maximum humidity. Such tests should be continued for the projected shelf-life of the product.

All tests on products for overseas markets need to be interpreted with caution. However clearly the market conditions are known and however closely the test conditions reproduce them, the conditions to which the product may be subjected during shipment are always unknown and can sometimes be very severe even when the market conditions are not particularly severe. For example, the temperatures in the holds of ships passing through the tropics may be extremely high.

It is seldom possible to give a general overall clearance of a product for all export markets. Even if the stability of the product is such that it has adequate shelf-life in the most severe market, it is likely that its shelf-life will be longer in markets having a less severe climate than in areas with more severe climates. In almost all cases it is suggested that specific clearance and a specific shelf-life should be given for a given product to a specific market, or group of markets. It is very often assumed, particularly by non-technical persons, that a product is tested for


stability and that after a certain time a result is obtained proving stability of the product and/or pack. In fact, however, stability testing is a predictive procedure based on data obtained from products stored under conditions which are believed to be likely to accelerate changes occurring at market conditions. As with all predictive procedures, they are not absolute but have a certain probability of success. This probability is lowest when based on short tests under conditions of high acceleration. The probability increases as the test conditions approach market conditions and the duration of the test is longer. Nevertheless, all have a probability of success which is less than 100%. In this sense a stability test is never finished in less than the actual shelf-life of the product. The point at which so-called ‘stability clearance’ can be given will depend on the product and on the information that is available on related products and experience in the market with such products.

It is further suggested that in reporting the results of stability tests and the conclusions drawn from them, care should be taken to avoid any statement which would lead people to believe that the products have been proved to be ‘stable’. The period for which the product can be expected to be stable under given conditions must also be specified. An accelerated stability study indicates only a probable shelf-life under given conditions; the longer the duration of the test the greater the probability.

CONCLUSIONS This paper has attempted to review the more important aspects of the testing of product stability and product-container compatibility. It has considered the objectives of stability tests, their planning, execution and the interpretation of the results obtained. The point that emerges most strongly is that there are no standard procedures to which all samples can be routinely submitted; to approach the problem in that way is inappropriate and inefficient.

In every test it is necessary first to define the objectives of the test and hence the information required from it; then the test is designed to yield that information. Time spent in careful planning at the beginning of a test can make the test more efficient and economical and save much time in its execution. Even when this has been done and the test is in progress, there should be sufficient flexibility to modify the test plan (eg, by changing examination schedules) in the light of information that becomes available as the test progresses. Control products or packages should always be used where possible. In short, every test is unique and should be so treated.

fundamentals of stability testing

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