Note: Descriptions are shown in the official language in which they were submitted.
= CA 02362756 2001-08-10
The present invention relates to sheet-like administration
forms for application as cosmetic, pharmaceutical or food-
technological products.
Flat-shaped administration forms for use in the oral region
and on the mucous membranes of the mouth are well-known.
Thus, US 3 444 858 (Russell, 1969) already describes me-
dicament strips based on a gelatine-like material.
In EP 0 216 762 a water-soluble film of starch, gelatine,
glycerine or sorbite is disclosed which is coated employing
a roll-coating method. The document shortly mentions in
this context that such dosage forms can also be produced
for chemical reagents, flavours and the like.
A formulation that is in principal suitable for making
sheet-like systems is disclosed in EP 0 460 588. Here, the
composition of 20 to 60 percent by weight of film former, 2
to 40% gelatinizing agent, 0.1 t 35 percent by weight of
active substance (here: flavouring agent) and a maximum of
40 percent by weight of an inert filler is regarded as af-
fording particular advantages.
DE 36 30 603 sees particular advantages in designing the
flat-shaped dosage form on a carrier material (release
film) so as to peelable in doses.
US 4 128 445 and 4 197 289 (Sturzenegger, 1978) address
possible technical solutions in connection with the loading
with active substances.
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For drug-containing sheet-like systems a two-layer struc-
ture of a water-swellable layer and a water-insoluble bar-
rier film is also regarded as advantageous (US 5 047 244).
In the manufacture of such films, some hydrophile film
formers, especially pullulan and other glucans, but also
cellulose derivatives, exhibit insufficient wetting on com-
mon coating media. This may result in premature or diffi-
cult substrate detachment as well as a resultant uneven
film thickness. As a remedy, US 4 562 020 recommends the
use of a substrate circulating in the process as a loop,
said substrate being based on nonpolar heat-stable polymers
and, during the process, being continuously subjected to a
superficial corona treatment, thus being constantly pro-
vided with a new polar surface that has a sufficiently safe
wetting capability. The drying temperatures are between 40
and 110 C; temperatures mentioned in the Examples are 60
and 85 C.
The aroma films produced on the pure film substrates have
proved disadvantageous because of their being smooth on
both sides. Such products have only limited suitability for
the further processing and use in stacks formed by film
cutting. Such stacks of film pieces or punched film pieces,
as are frequently offered to the consumer in suitable dos-
age dispensers, tend to stick to each other, which makes it
much more difficult to safely remove the pieces. As such
film-shaped administration forms, due to their small weight
per unit area (typically approx. 10 to 80 g/m2) tend to be-
come statically charged, and since, at the same time, their
surfaces, to facilitate later removal, are designed so as
to be slidable on each other, this aspect is disturbing not
only in use but also in the process technology.
A third demand that should be met by the process is that
loss of flavour due to heat be prevented while affording
CA 02362756 2001-08-10
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maximum process rates. The prior art reveals no information
pointing towards a solution to this demand.
From these requirements, which have as yet remained un-
solved in the prior art, results the object of the present
invention of providing processes for making sheet-like ac-
tive substance carriers which enable a precise and repro-
ducible coating quality, prevent the mutual adhesion of the
finally produced pieces of film or sheet in the stack, and
can be obtained, while avoiding contamination and excessive
thermal load, at high production rates.
This object is achieved according to the present invention
in that immediately subsequent to the coating of the solu-
tion of hydrophile polymers with added active substances
and further auxiliary substances, a stream of moderately
warm air (30 - 50 C) is passed over the material, where-
after the temperature is raised slightly (35 - 80 C), fi-
nally followed by a reconditioning phase at 25 - 50 C. The
process rate is advantageously regulated such that a rela-
tive substrate humidity (equivalent humidity or equivalent
air humidity) of 50 - 75% relative humidity, preferably 60
- 68% relative humidity, is maintained in all cases.
By using rough-surface substrates, preferably thermoplasts
of polypropylene, polyethylene, polyethylene terephthalate,
polycarbonate, and laminates of these polymers, with poly-
ethylene-coated paper being particularly preferred, it is
effectively prevented that the later-produced single film
pieces stick to each other in a stack.
The process according to the invention is applicable to any
form of flat-shaped products - for example, for use as a
food stuff, medicament or a cosmetic - which can be pro-
duced in a coating process from a mass which has been flu-
idized by solvents, especially water, and contains solid,
CA 02362756 2001-08-10
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hydrophile base substances and optionally further compo-
nents.
These hydrophile base substances may be polymers such as
starch and its derivatives, agar-agar, gelatine, cellulose
and cellulose derivatives, alginic acid, galactogluco-
mannan, carrageen, other vegetable gums permitted for the
respective field of application, pullulan and other glu-
cans, dextrane, and polyvinylpyrrolidone, polyvinyl alcohol
or polyacrylic acid homopolymers and copolymers. The poly-
vinyl alcohol used is advantageously a partially hydrolised
form wherein between 1 and 20%, especially preferred: ap-
proximately 12%, of the hydroxyl groups are replaced by
acetyl groups.
The process according to the invention is effective in par-
ticular with problematic masses containing high portions of
pullulan, carrageen or cellulose esters.
Hydrophile additives of small molecular weight may also be
employed, as structure-forming agents; these mostly serve
to achieve application-specific objects. Possible additives
are, inter alia, sugar, sugar alcohols, sugar substitutes,
organic acids, polyethylene glycol.
Solid substances which due to their poor solubility do not
form a molecular-disperse mixture or solution in the base
material may also be contained. Suitable substances are,
for example, carbonates, phosphates, silicates, or sulfates
of the alkali earth metals, zinc oxide, titanium oxide or
other colour pigments, talcum, lactose, cyclodextrins or
starch and starch derivatives, as far as they form their
own, solid, disperse phase in the final product.
The above list is exemplary only and can be completed by
substances of the same function known to those skilled in
the art.
CA 02362756 2001-08-10
Active components may, for example, be medicinal or cos-
metic active agents, dietary additives to foods, colourants
or diagnostics. In particular, the process according to the
invention can be employed with flavouring agents which are
otherwise difficult to process because of their volatility.
The flavours which may be used with this invention are
mainly essential oils (volatile, water-insoluble distil-
lates of fragrant components of plants) and other volatile,
fragrant substances having a limited miscibility with wa-
ter. Examples therefor are phenyl ethanol as a component of
rose fragrance aromatics, menthol, eucalyptol (cineole),
camphene and pinene in peppermint-like fresh flavourings,
appetite inducing flavourings (spicing aromatics) such as,
for example, n-butylphthalide or cineole, but also flavours
having medicinal applications, such as eucalyptus oil,
thyme oil, methyl salicylate, terpentine oil and camomile
oil.
A very broad field is taken up by essences and aromatics
which are being used as additives in foods, and in prefab-
ricated food additives. Examples for these are the so-
called fruit ethers, but also other aromatics such as ethyl
vanillin, 6-methylcoumarin, citronellol or n-butyl acetate.
Additives of surface-active substances can improve the uni-
formity of the distribution of the droplets of aromatics.
In special cases it may prove to be of advantage to apply
one or more further layers of equal or different composi-
tion, in order to obtain special surface or tensile proper-
ties, for example.
The mass is prepared, for example, by strewing-in, knead-
ing-in or slowly digesting the solid components in the sol-
vent (typically water, but also, e.g., ethanol, acetone and
other compatible, physiologically acceptable solvents and
mixtures thereof are employed). To this phase is added,
CA 02362756 2001-08-10
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while stirring slowly, the pre-weighed amount of flavouring
agent and other liquid, lipophile additives, as far as pro-
vided by the recipe.
In the interest of the object of the invention, it has
turned out to be of great advantage with respect to a uni-
form constitution to homogenize the mass, prior to coating,
on a high-speed homogenizer.
In the process according to the invention, the mass is
coated on a substrate using a spread-coating, knife-coating
or extrusion method, and is dried in a drying canal con-
sisting of at least three independently temperature-
controlled zones.
The substrate may in principle consist of substrates known
to those skilled in the art and widely used, such as, for
instance, polyethylene terephthalate, polyethylene, poly-
propylene, polycarbonate, polyurethane. Also used are lami-
nates of these substances with other polymers, paper, fi-
breglass, and other structure-forming materials for in-
creasing tensile strength. To regulate surface adhesion it
may be useful to take measures such as siliconization,
fluorination, acid treatment or corona treatment, but these
require clarification of their physiological tolerance for
the relevant purpose of application in each individual
case.
Special advantages are achieved according to the invention
if the surface facing towards the coating mass does not
have a smooth contour, but a contoured, dulled, and in any
case rough-surface contour. The peak-to-valley height can
be in the range of 0.1 Un to about 10 pm, preferably be-
tween 0.5 and 3pn. of advantage are rounded protrusions in
the microstructure, which further reduce sliding friction.
The object of the present invention is regularly achieved
where the drying takes place at a process temperature which
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rises initially and is then, in the last zone at the lat-
est, reduced by 10 C.
Advantageously, the process rate is to be adjusted such
that a product having an equivalent humidity of 50 - 75%
relative humidity, preferably 60 - 68% relative humidity,
is obtained.
Under these process conditions the products obtained proved
surface-stable, flexible and break-resistant as well as
largely tear-resistant. The resultant surfaces exhibit vir-
tually no "cold flow" and are thus basically dimensionally
stable. The film can be removed from the support without
perceptible elongation occurring, and can be further proc-
essed separately.
The equivalent air humidity is determined as follows: A
freshly prepared product strip of about 0.1 m2 in area is
immediately and quickly folded, using rubber gloves, and
placed in a wide-neck glass vessel, the cover of which is
provided with a through-bore such that the rneasuring head
of a hygrometer is introduced therein. After about a min-
ute, depending on the construction of the device, the meas-
ured value can be read.
The further processing takes place, after longitudinal sec-
tion, in punching devices or simply by transverse section.
The sheet-like products produced preferably have a thick-
ness of between 20 and 300 pm; their size may advanta-
geously range from 0.5 to 12 cm2. Subsequent packaging may
take place singly or in a stack, for example in sealed
pouches or dosage dispensers.
