Medicinal and Aromatic Plants—Industrial Profiles

Partitioning Effect in Formulated Products

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Partitioning Effect in Formulated Products
It is well accepted that the anti-microbial activity resides in the aqueous phase of a preserved
two phase system and is therefore dependant on the equilibrium concentration of the
preservative in this phase. It is expected that tea tree oil will partition between the oil and
water phases present in a two component system in accordance with the partition coefficient
and the relative ratio of oil and water in the system. To estimate the likely concentration in
the aqueous phase of a simple two component system, the partitioning behaviour of tea tree
oil between water and Crodamol GTCC (Caprylic/ Capric triglycerides, a typical oily
component of cream formulations) was investigated. The effect of surfactant concentration
was also noted.
Initial aqueous solutions were prepared using polyoxyl 35 castor oil. The ratio of surfactant
to tea tree oil varied between 1:1 and 1:3 on a weight basis and no surfactant as a control.
The solubilised mixtures were mixed with an equal volume of Crodamol GTCC and the
final concentration of tea tree oil in the mixture was 0.5%. The mixtures were mixed on a
vortex mixture and allowed to equilibrate over 3 days with occasional shaking. The
distribution of tea tree oil in the aqueous phase was determined by GC assay of terpinen-4-
ol in the aqueous phase after centrifugation. The results were as follows:
Tea tree oil concentration
With surfactant
Without surfactant
With no surfactant present nearly all the tea tree oil had migrated into the oil phase. In the
presence of the surfactant the concentration of the tea tree oil in the aqueous phase remains
at about 0.4%. The partitioning appeared to be independent of the concentration of the
surfactant in the range studied. This has important implications for formulated products. It
is thus essential that appropriate microbial evaluation be undertaken for all tea tree oil
products. It is recommended that specific organisms be used depending on the use of the
product e.g. Propionibacterium acnes and Candida albicans for acne and antifungal products
Perhaps as important as microbial evaluation is the need for stability testing on the final
formulation in the proposed pack for marketing. Glass, whenever possible is the most
appropriate for tea tree oil products. In low-density polyethylene (LDPE) a loss of terpinen-
4-ol occurs at room temperature after 3 months. At 45°C after 3 months, the terpinen-4-ol is
barely detected. Even with low concentrations of tea tree oil the oil migrates through LDPE
walls and the solvent attacks the external features on the container such as the label print.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

High-density polyethylene has been reported to be satisfactory for products containing
around 20–25% tea tree oil. The maximum concentration acceptable will be a function of
the nature of the product and the wall thickness of the plastic. Deformation has also been
reported due to reactions between tea tree oil and plasticising resins. If plastic caps are
employed it is important to use impenetrable liners.
The Pure Oil
Tea tree oil is reasonably stable at room temperature when stored in brown glass or stainless
steel. It is however sensitive to heat, light and air. On storage there is a drop in terpinen-4-
α-terpinene and γ-terpinene and an increase in p-cymene. High levels of this compound
can indicate poor storage, old oil or bad extraction techniques. The use of antioxidants in
long term storage should be considered.
Formulated Products
The importance of adequate stability testing on the final product in the proposed marketing
container cannot be overstated. Batches should be stored at 4°C, 30°C, 40°C and possibly
cycling temperature conditions and monitored at regular intervals for appropriate physical
characteristics. Chemically, it is suggested that terpinen-4-ol, cineole and oxidation products
are monitored and preservative efficacy testing is performed at the beginning and end of the
stability study.
Reasons for products failing stability testing are many and varied. Most product failures
in the past have been associated with the use of packaging incompatible with the product
components and poor stability testing prior to product launch. This has resulted in several
unsatisfactory products from a physical viewpoint. Problems which have occurred
include panelling of bottles and migration of tea tree oil through pack walls resulting in
deformation of external decorations such as label print. Regulatory authorities have
given little attention to chemical or microbial activity of formulated products as most
of the product claims which have appeared are limited to simple antibacterial claims
rather than treatment for specific conditions such as candidiasis or acne. However, as
clinical testing on formulated products increases there will be increasing attention to
the role of formulation in the effectiveness of tea tree oil for specific conditions. The
main points to consider in product failure from a performance point of view are: (1)
inadequate packaging, (2) inactivation of tea tree oil by solubilisers, surfactants and
other excipients, (3) the grade of tea tree oil used and (4) the method of manufacture
including the order of addition of the components.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

The inherent anti-microbial properties of tea tree oil are advantageously offered in formulated
products. Because of the properties of the constituents of the oil, great care must be taken
with solubilisation, formulation, stability and packaging to ensure maximum utilisation of
the bioactivity of the oil.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

G.R.Davis Pty. Ltd. Warriewod, Australia
Tea tree oil is not a new crop in that it was first discovered by Arthur Penfold in the 1920s
(Penfold 1925) and commercial production started soon after.
The oil was sold as pure oil and also in products such as in disinfectants and tooth paste.
The oil and products were sold mainly, but not exclusively, on the Australian market.
In the 1950’s there was a swing away from natural products towards synthetic preparations,
and the demand for tea tree oil fell. The oil was still produced and used as before to a limited
extent, but was also used to enhance nutmeg oil and as a source of terpinen-4-ol.
The industry maintained a five to fifteen tonnes per annum production rate until the
1980’s by when there was a swing back to natural products. It was at this stage that the tea
tree oil industry started to develop into a substantial industry. It is because of the very small
production in the previous years, the rapid establishment of plantations and the marketing
of a wide range of new tea tree products in the early 1980’s, that the marketing of tea tree oil
can be regarded as marketing a new product.
There are normally three stages in the production and marketing of new agricultural products.
As soon as it becomes apparent that the product can be grown and marketed, there is a rush
to produce it (stage 1). This is often followed by over production, where the demand does
not increase as rapidly as production (stage 2). The third stage is that the less efficient and
the overcapitalised producers fail and production and demand eventually reach an
equilibrium. The price of the oil is then no longer set by supply and demand, but by the
lower level of cost of production, distribution etc. including profit margin.
At this stage (early 1997), the industry may be near the end of stage 1. Production has
increased greatly. Markets have also increased, but, considering the vast area planted, they
might not expand at the same rate as production. Therefore the market trend will be towards
lower prices, unless some large scale new uses for the oil are found. If the market does
develop at a rate sufficient to absorb the greatly increased production, prices will not fall.
The average price for tea tree oil on world markets and estimates of annual production over
the last 15 years is shown (
Figure 1
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

The industry was fortunate in that, in the early years of the new development, one
company took a very large proportion of the oil produced. This company has now reduced
its intake substantially. The steady growth of the market is encouraging, but the growth in
production is such that overproduction is likely. Even a small excess of oil on the market
will have a depressing effect on price.
In order to avoid a downward price trend it is necessary to attain a reasonable balance
between supply and demand. The desirable and positive way is to increase sales of the oil,
with concomitant change in plantation establishment.
In recent years tea tree oil sales have increased in sympathy with the increased popularity of
natural products. If synthetic products are developed which are very effective in the field
now serviced by tea tree oil, the trend might be away from tea tree oil, unless it can be
demonstrated that this oil is effective as well as natural. To do this, hard scientific evidence
is required. Fortunately, considerable R & D effort is at present being expended to demonstrate
the value of the oil.
The history of new products generally is such that unless, after the initial euphoria, they
are perceived to be more effective than competing products, they will fade from the market.
Tea tree oil has a number of natural advantages, only some of which are being used by
the industry. It has a wide range of uses, mostly antiseptic. It has been demonstrated that the
oil is effective in controlling a number of the common human pathogens. Consequently, in
Figure 1 Estimates of tea tree oil average price (in Australian Dollars) and production (in tonnes per
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

the early stages of its revival it was promoted as a “cure all”. While the oil has a good claim
to this description, the market is limited for such products. To cover the whole range of its
useful capacity, the oil must also be sold for specific purposes where scientific clinical
evidence of its efficacy can be given. The market today, except for a small section, is too
sophisticated to believe in the “cure all” product.
One of the strengths of tea tree oil is that it is not a narrow single purpose product.
Research is showing that different chemotypes of the oil are effective against different
pathogens. With considerable variation within the Melaleuca-terpinen-4-ol type oil there is
scope for producing oils suitable for a number of purposes, thus broadening the potential
market for this oil.
The industry in general has endeavoured to reduce the genetic potential for tea tree oil by
trying to restrict its production to one species, even though at least three species and possibly
more, have oil that is almost identical. Even within the one species most commonly grown,
limits on the composition of suitable oil, particularly the cineole content, have been advocated,
unfortunately successfully, without any scientific evidence to support the limits. This is
contrary to the general concept of maintenance of genetic diversity, and eventually must
have an impact on good market practice. At this stage of the industry’s development it
would be inadvisable to restrict genetic potential.
The advantages of working with a genetically variable natural product include the potential
for both intra and inter-specific breeding. If the market trend for tea tree oil is to be upwards,
a broadening of the range of products is required, and this may be achieved by the
development of some specific purpose products.
There are few, if any, major agricultural crops today that have not been substantially
modified and improved by selection or breeding. If tea tree oil is to fulfil its potential and so
increase its market, selection and breeding will occur. As researchers identify which
chemotype of the oil is most effective against a particular pathogen, market development of
the chemotype will occur. Chemical modification of the oil is one possible method, but in
this age of the veneration of nature, producing a natural oil which does the job is better for
marketing purposes. To rule out the opportunity of interspecific breeding by confining tea
tree oil to one species would be to limit the industry’s potential.
The market for tea tree oil at present has a healthy upward trend, but this will be harder to
maintain as the oil displaces other products now being sold. The manufacturers so affected
will offer improved products against which tea tree will have to compete. It is therefore
essential to keep a positive approach to marketing tea tree oil. Its virtues should be
emphasised, yet there is now in the industry an active campaign to rule out top quality oil if
it has more than a very small percentage of cineole.
Cineole probably enhances the activity of the oil against certain micro-organisms
(Southwell et al. 1993), possibly by increasing the oil’s capacity to penetrate tissue to reach
lesions on which it is acting. Contrary to previous reports, recent scientific evidence suggests
that cineole has no significant skin irritant properties. For example Southwell states:
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

In conjunction with the Skin and Cancer Foundation in Darlinghurst in Sydney, we began
investigations into the skin reactions of cineole and tea tree oil. Cineole, under the synonym
eucalyptol, had previously been tested on both human and animal subjects and found to
cause neither irritation nor sensitisation (Opdyke 1975). Our studies confirmed this finding
(Southwell 1996).
Also, further studies show:
There is no evidence to support the current industry misconception that tea tree oils with
ultra low levels of 1,8-cineole are superior to oils with higher levels of cineole. Standards
specifying a minimum level for terpinen-4-ol and a maximum level for cineole have been
interpreted wrongly to mean that terpinen-4-ol and cineole concentrations must be maximised
and minimised respectively. Cineole, in concentrations above 15%, is undesirable because
of the concomitant decrease in terpinen-4-ol, the active ingredient. However, recent
investigations have confirmed that cineole in concentrations up to 15% is not detrimental to
the oil, as it is neither a skin irritant nor an antagonist to the activity of the oil (Southwell et
al. 1996).
As well as the references listed, one has only to consider that there is more than 10 times as
much eucalyptus oil as tea tree oil sold in the world, most of which has at least 10 times as
much cineole, yet eucalyptus oil is not a skin irritant.
Preliminary work has indicated that some natural tea tree oils of higher cineole content,
but still within the ISO Standard, are more effective against certain pathogens. The possibility
that antifungal and anti-helminthic activity may be enhanced by cineole has been reported
by Southwell et al. (1996). If this proves correct, the proponents of very low cineole oils
will have painted themselves into a corner.
If the market trend for tea tree oil is to continue upwards, the industry must cease to
promote the fear campaign which specifies that one of the main compounds of the oil is
dangerous. Such a proposal could be taken up by non tea tree oil competitors to the great
disadvantage of the industry.
The major outlet for tea tree oil to date is the cosmetic field, as a general disinfectant, and as
pure oil for first aid use. Although further development of these markets will occur, expansion
is limited because of the difficulty of obtaining regulatory approval to make claims for the
efficacy of the oil. Success in this endeavour, which must eventually be achieved, will open
new markets for the oil. Registration in various FDA monographs, therapeutic goods registers
and pharmacopoeias must be obtained to allow markets to be fully developed. This long
and costly process is under way and its outcome will have a substantial effect on market
Nevertheless, to be able to sell oil and make claims in the “pharmaceutical” field will not
result in a great increase in markets, unless the oil can be shown to be not only efficacious
but at least as good, and preferably better than other products. While the oils’ “natural”
status is highly regarded in the cosmetic field, the main criterion in the medical field is that
the oil must be effective.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

In order to sell pure oil in most countries it is necessary that the oil is in accordance with an
authoritative standard. Physical constants for the oil were established in the British
Pharmaceutical Codex 1949. Because of the physical standard range, this BPC standard
confined tea tree oil to the low cineole form of Melaleuca of the terpinen-4-ol type. That is,
oil containing not more than about 15% cineole, and the market accepted oil sold on this
standard for many years. An Australian Standard was established in 1967 (K175). This
standard also established physical constants only, and these were close to the BPC standard.
The Australian Standard was revised in 1985 (AS 2782) and the physical constant range
altered slightly to accommodate oil from M. alternifolia outside the previous range. This
enabled the inclusion of natural high quality M. alternifolia oil which the previous standard
had ruled out. AS 2782 brought in chemical composition for the first time by stipulating a
maximum cineole and a minimum terpinen-4-ol content. The standard also increased its
definition to include oils from other species of Melaleuca, provided the oil conformed to
the rest of the standard. This was done because the chemical composition of the oil of some
of the species is almost indistinguishable from that of M. alternifolia. A further review of
the standard in 1995 stipulated limits to a number of compounds in the oil and this same
standard has been published by the International Standards Organisation as ISO 4730E
(International Standards Organisation 1996). It has also become the Australian Standard.
Tea tree oil is marketed in accordance with these standards. While the standards effectively
specify the oil, they are also sufficiently broad to allow development of special purpose
types of oil.
While initially the oil was used in the pure form or as a 50% or stronger solution, it
was soon recognised that oil in quite low concentration was a very effective antiseptic.
This gave rise to a wide range of products containing tea tree oil, and means that a lot
of tea tree oil is sold as a minor, though usually the active ingredient of the product.
Because of the effectiveness of the oil in low concentration there is good scope for
value adding, which is more profitable than selling the oil in the pure form (see
Chapters 11
Tea tree products available on the market include neat oil, 15% solutions, shampoos,
liquid and bar soaps, bath oil, handcreams, antiseptic creams, mouthwashes, toothpastes
acne products, tinea creams and powders, vaginitis creams and douches, burn creams and
various other health and veterinary care products.
Any oil which is in accordance with the standards should be sold as good quality Australian
tea tree oil. To specify grades within the standard is counter-productive as the instinctive
reaction of the buyer is that if there are grades within the standard, some oil within the
standard must be inferior.
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,
part of The Gordon and Breach Publishing Group.

When specific purpose oils are developed, they will need to be labelled as such, but in
the meantime the industry would be ill-advised to downgrade, even by inference, oil
which meets the standard. To keep the market on an upward trend, the industry as a whole
needs to promote Australian Tea Tree Oil; the essential oil of Melaleuca terpinen-4-ol
type. To infer that there are lower grades of this oil, an inevitable consequence of stating
that there are superior grades, is a bad marketing principle, particularly as there is no
credible evidence to show that any oil that conforms with the standard is superior to any
other oil that conforms.
To claim that only some ISO standard tea tree oil is pharmaceutical grade is a bad market
strategy. Buyers who do not need the oil to be pharmaceutical grade will demand a lower
price for non pharmaceutical grade, whereas all oil within the standard is pharmaceutical
grade and should be promoted as such.
The price of tea tree oil on world markets is one of the great challenges confronting the
industry. At present, the price is adequate to sustain current methods of production. However,
with production increasing rapidly, market expansion needs to keep pace with the rapid
increase in planting or prices will fall.
The more successful the industry is in promoting tea tree oil and its products, the more
countries will attempt to produce oil to share the market. Thus, even a substantial increase
in use of the oil world wide will not necessarily absorb the whole Australian production. In
fact, at this stage (early 1997) this is not just a theoretical possibility as production outside
Australia is established and growing. Australia, however, has advantages that should ensure
pre-eminence on the world market. No other country can claim “country of origin status”
and the fact that production methods are so well developed and researched means that
Australian-produced oil should remain superior. There is a tendency at present for some
sellers to try to increase their market share by denigrating the oil of other producers. It is
very unlikely that any substandard oil is offered abroad. If so, market forces will rapidly
eliminate this from the market.
If some countries develop large production capacities, the market trend, in terms of price
of oil, will almost certainly be downwards. However, a substantial price reduction would
result in an upward market trend in volume of oil sold, as one of the restrictions on market
expansion at present is the high price of this essential oil.
Some countries have maintained pre-eminence, or even exclusive production of an
essential oil, due to peculiar soil or climate conditions or closely guarded plant varieties
(e.g. French lavender oil). This is not the case with tea tree oil. Oil is already available from
other countries, and seed has been widely distributed. The strategy of establishing a higher
standard for a national oil that other countries cannot meet has already been frustrated, at
least for the immediate future. There is no sense in setting a higher, i.e. tighter or more
restrictive standard, if competing countries can meet it. This is simply counter productive. It
again emphasises the futility of offering grades of oil within the standard. If competitors
can meet the top grade, then all other grades will be accepted as inferior, and, it is bad
marketing if any ISO standard oil is offered as other than finest quality. In any case, it is
Copyright © 1999 OPA (Overseas Publishers Association) N.V. Published by license under the Harwood Academic Publishers imprint,

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