Note: Descriptions are shown in the official language in which they were submitted.
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DESCRIPTION
CLOSURE COATING
TECHNICAL FIELD
~ The present invention relates to the field of
coated elastomeric closures and methods of making the
came .
BACKGROUND ART
Elastomeric elements such as plugs, stoppers,
"o"-rings, gaskets and others are used to provide fluid-
tight seals. Elastomeric elements which can be used toprovide fluid-tight seals are referred to herein as
"closures."
One application for elastomeric closures is in
sealing pharmaceutical vials. An elastomeric closure
lS for a pharmaceutical vial typically is in the form of a
stopper which includes a relatively thick-walled rubber
ring with flat top and bottom surfaces encircling a
relatively thin septum formed integrally with the ring.
Such a stopper may also include a hollow, cylindrical
collar projecting ~rom the bottom surface of the ring
and surrounding the septum. In use, the stopper is
placed on the mouth of a pharmaceutical vial so that the
collar enters into the mouth of the vial and maintains
the septum in alignment with the mouth. The ring
overlies the rim of the vial surrounding the mouth. A
metallic element is clamped over the rubber ring and the
vial rim so that the metallic element holds the bottom
surface of the ring against the vial rim.
The bottom surface of the ring serves as a
sealing surface. This surface on the stopper conforms
to minor irregularities in the vial surface under the
pressure applied by the metallic crimp element.
Many other elastomeric closures are used in
the pharmaceutical industry and in other industries. In
each case, however, a sealing surface of the closure
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conforms to a mating surface of a container or other
object to make the fluid-tight seal.
Coatings have been applied on elastomeric
closures such as pharmaceutical vial stoppers to reduce
S the coefficient of friction of the stopper~. This
facilitates handling and feeding of the ~toppers in
automated equipment and facilitates engagement of the
stoppers with the ~ials. Coatings may also provide a
barrier against extraction of materials from the closure
by the product stored in the container. One type of
coating includes a liquid lubricant such as silicone
oil, glycerine or the like disposed on the surface of
the closure but not bonded to the closure itself. Such
coatings are unsatisfactory in many applications due to
cont~r;n~tion of the product in the vial by the coating
material, and by materials extracted from the stopper.
Also, liquid coatings can diffuse into the elastomer
itself, thereby re~oving the coating from the surface.
This may cause inconsistent results in processing.
Other at~empts have been made to provide
stoppers coated with polymeric materials such as
polytetrafluoroethylene, polyethylene, tetrafluoro-
ethylene, polypropylene and polyparaxylylene. These
materials generally reduce the coefficient of friction
of the stopper and generally reduce contamination of the
product in the vial. However, these coatings tend to
impair conformance of the closure to imperfections in
the vial, resulting in leakage problems. This effect is
described in the article "Quantative and M~h~n;~tic
Measurements of Parenteral Vial Container/Closure
Integrity - Leakage Quantitation, by Morton et al, J.
Parenteral Science and Technology, 43:88 - 97 (1989).
Thus, there is a need for a closure coating
which is chemically inert and which does not contaminate
the product; which provides a substantial reduction in
coefficient of friction; and which does not
substantially impair the ability of the elastomeric
_ _ _ _
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closure to seal. ]?referably, the coating should also
retard extraction of materials from the elastomer by the
product or at least should not itself contribute
extractables. All of these requirements, taken together,
S present a formidable engineering task.
Despite considerable effort expended by those
in the art, there has remained a significant, unmet need
for improved coated closures and for improved methods of
coating closures.
10 SUMMARY OF THE INVEINTION
The present invention addresses these needs.
One aspect of the present invention provides a
method of making coated elastomeric closures
characterized by the steps of providing uncoated
elastomeric closures and plasma polymerizing a lower
alkene to form a coating on the uncoated closures to
reduce the coefficient of friction of the closures. The
coef~icient of friction of closures is commonly
expressed in terms of the "slip angle", i.e., the angle
to the horizontal at which a plane or channel bearing
the closures must be positioned before the closures will
slide down of their own accord. Most preferably, the
plasma polymerizing step is conducted in a gradual
manner, so that the slip angle of the closures decreases
from the value for the uncoated closures to about 45
over a period of at least about 15 minutes. Typically,
the uncoated closures have a slip angle of at least
about 60. Although the rate of decrease of the slip
angle during the process will vary during the process,
the average rate of decrease over the entire process
desirably does not exceed 2 degrees per minute, and more
desirably is about 1.5 degrees per minute or less. The
lower alkene desirably is selected from the group
consisting of ethylene, propylene and combinations
thereof, most preferably propylene. The plasma
polymerization step may include the steps of providing a
gaseous mixture of the lower alkene with inert gas and
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forming a low temperature plasma of the gaseous mixture
in contact with the closures.
This aspect of the present invention includes
the realization that the rate and conditions of plasma
S polymerization have a substantial influence on the
properties of the coated closure. A coating applied
gradually, in a slow polymerization process requiring
considerable time to reach a given slip angle, normally
will have lower leakage than a closure coated to the
same slip angle but using a rapid polymerization
process. Although the present invention is not limited
by any theory of operation, it is believed that this
dif~erence is relal_ed to the extent of cross-linking
induced by rapid and slow processes. That is, it is
believed that slower processes tend to yield coatings
with less cross-linked polymeric structures whereas
rapid processes tend to yield more cross-linked
coatings. Regardless of the reason, however, the
closures produced by the slow process with a relatively
slow rate of polymerization and with slow rate of
decrease in the slip angle of the closures have better
leak resistance than equivalent closures produced with a
rapid polymerization process.
Typically, the gas mixture is converted to a
piasma by applying electrical energy, such as RF or
microwave energy so as to produce a glow discharge in
the plasma adjacent the closures. The closures may be
in a pile within a reaction vessel maintained under
~ubatmospheric pressure so that there are interstices
between the closures. The plasma may be formed within
these interstices. Typically, the glow discharge fills
about one-fourth to about three-fourth of the
interstices in the pile. The pile may be agitated
during the plasma-forming step, as by rotating the
reaction vessel around a horizontally-extensive
rotation axis so as to tumble the pile. In a
particularly preferred arrangement, the reaction vessel
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is also pivoted around a horizontally-extensive pivot
axis transverse to the rotation axis ~o as to further
- tumble the pile, and cause the closures to circulate in
directions parallel to the rotation axis. The gas
mixture flows through the reaction vessel generally
codirectionally with the rotation axis. Because the
closures circulate, no single closure remains in the gas
inlet region where the gas mixture is rich in alkenes,
or in the outlet region where the gas mixture is alkene-
depleted.
Further aspects of the present invention
provide coated elastomeric closures. Most desirably,
the coated closures are made in accordance with
processes as aforesaid. The coated closures desirably
lS include an elastomeric body, such as a body consisting
essentially of rubber and defining a sealing surface, at
least the sealing surface being covered by a plasma
polymerized lower alkene such as plasma polymerized
ethylene or plasma polymerized propylene. Most
preferably, closures according to this aspect of the
present invention have a slip angle of less than
about 30O and desirably about 28 or less.
BRIEF DE8CRIPTION OF T~E DRAWINGS
Figure 1 is a diagrammatic view of apparatus
in accordance with one embodiment of the invention.
Figure 2 is a sectional view of a closure
together with part of a test fixture.
Figure 3 is an elevational view of a test
figure.
~EST MODES OF CARRYING O~T THE lNv~lloN
Apparatus in accordance with one embodiment of
the present invention is illustrated in FIG. 1. The
apparatus includes a hollow, tubular cylindrical
reaction vessel 10 formed from glass, the reaction
vessel having a central axis 12. The inlet and outlet
ends 14 and 16 of the reaction vessel are closed by end
panels 18 and 20 respectively. The end panels are
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arranged so that the same can be readily detached from
the reaction vessel and reattached thereto to permit
access to the interlor of the reaction vessel. The end
panels of the reaction vessel are equipped with
conventional seals (not shown). Reaction vessel 10 is
mounted in circular journals 22. ~ournals 22 rest on
rollers 24, which in turn are supported for rotation on
a frame 26. Rollers 24 are connected to a rotation
drive motor 28 so that motor 28 can drive the rollers
lo and rotate vessel lo around the central axis 12.
Frame 26 in turn is pivotally mounted to a subframe 27
by a pivoted joint, schematically indicated at 30. A
reciprocating linear actuator 32 is connected between
the subframe 27 and a point on frame 26 remote from the
1S pivot joint 30 so that the reciprocating actuator will
cause the frame 26 to rock, relative to subframe 27,
around a pivot axis passing through pivot joint 30. The
pivot axis is transverse to the axis 12 of the reaction
vessel; as seen in Fig. 1, the pivot axis extends into
and out of the plane of the drawing through pivot
joint 30.
Gas supply apparatus 36 includes a plurality
of gas sources 38 each connected by a valve 40 to a
manifold 42. The gas sources themselves may include
conventional elements such as storage tanks containing
the desired gases, pressùre regulators, flow meters,
safety valves, purge valves and the like. As further
discussed below, some or all of the gas sources may be
actuated together so as to supply a gas mixture
containing the required reactants. Manifold 42 is
connected through a flexible bellows 44 and a rotary
joint 46 to an inl~et port 48 in end panel 20, at the
inlet end of vessel 10. An outlet port 51 in end
panel 18 at the outlet end 14 of the vessel is connected
through a similar rotary joint 48 and flexible
bellows 50 to an e.xhaust system 52 which includes a
vacuum pump and conventional auxillary equipment. The
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gas supply systems and exhaust systems also include
conventional control elements such as pressure,
temperature and flow rate sensors, programmable
controllers and the like. These elements are also
S linked to conventi~nal control elements (not shown)
arranged to control the operation of motor 28 and linear
actuator 32. A blower 54 is connected to a cooling air
manifold 56 disposed adjacent the exterior of vessel 10.
The cooling air manifold may, for example, be mounted on
frame 26.
A helical metallic coil electrode 58 encircles
vessel 10, the coil being spaced slightly outside of the
exterior of the vessel. The coil is fixed to frame 26,
and does not rotate with the vessel. The ends 60 of
lS the coil are electrically connected to ground potential,
whereas a center tap 62 at the middle of the coil is
electrically connected to the output of an impedance
matching network 64. The input of network 64 is
connected to a conventional radio frequency
generator 66. The impedance matching network may be of
conventional construction and may include elements such
as variable capacitors and/or inductors. As is
conventional in the RF plasma art, the impedance
matching network is adjusted for efficient power
transfer between the RF generator and the coil, and
between the coil and the plasma as discussed below.
The RF generator 66 can be arranged to operate
at any suitable frequency, typically between about 100
KHz and about 300 MHz. However, the generator
preferably is set to operate at a so-called "ISM" or
industrial-scientific-medical frequency as required by
radio communications authorities. 13.56 MHz is a
particularly preferred ISM fre~uency. Vessel 10 and
coil 58 are surrounded by a grounded metallic shield 68,
only partially illustrated in FIG. 1. The shield may be
provided with appropriate openable access panels (not
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shown) for access to the end panels 18 and 20 on the
vessel.
In a method according to one embodiment of the
invention, uncoated elastomeric closures are disposed
S within the interior of vessel 10 by opening end panel 16
and resealing the end panel. The closures may be
closures of any shape which can be used to provide fluid
tight seal, but most preferably are closures of the type
used for sealing pharmaceutical vials and other
containers. Closures intended for sealing mouth
openings on common pharmaceutical vials are referred to
herein as "stoppers". As illustrated in FIG. 2, a
typical stopper includes a relatively thick ring
portion 80 defining a top surface 82 and a bottom
lS surface 84, a hollow cylindrical protrusion 86 extending
from the bottom surface and a relatively thin
puncturable diaphragm or septum 88 aligned with the
interior of the hollow cylindrical protrusion.
Closures such as stoppers typically are formed
from rubber compositions including polymers such as
butyl rubber, natural and synthetic polyisoprene,
silicones and combinations of these together with
vulcanizing or cross-linking agents, catalysts,
retarders, pigments and the like. The rubber
composition may also include particulate fillers such as
carbon black and others. Alternatively, the closures
may be formed rrom non-rubbeL elasto,ller s such as
thermoplastic and thermosetting polyurethanes, and other
synthetic polymers having elastomer properties. These
materials may also be blended with additives and
fillers. Accordingly, as used herein, the term
"elastomer" refers 1_o any composition having elastomeric
properties, regardless of whether the same includes
rubbers or other polymers.
3S In the coating process, the closures 80 are
placed within the interior of vessel 10 so that the
closures form a pile 90 in the bottom of the vessel.
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The closures in the pile Will define interstices 92
therebetween. The shapes and sizes of these interstices
will depend upon the shapes and sizes of the closures
and upon the random arrangement of the closures in the
pile.
After sealing the chamber, exhaust system 52
is actuated to bring the chamber to a sub-atmospheric
pressure, preferably between about o.Ol and lO Torr, and
more preferably between about O.l and l Torr. Gas
supply unit 36 is actuated to provide a gas mixture
including at least one lower alkene. As used herein,
"lower alkene" refers to unsaturated hydrocarbons and
hydrocarbon derivatives including between 2 and 8 carbon
atoms, preferably between 2 and 5 carbon atoms and most
preferably 3 carbon atoms. Propylene is particularly
preferred. Mixtures of alkenes may also be employed.
The gas mixture also includes a monoatomic, Group VIII
gas, commonly referred to as an inert gas. Helium and
argon are preferred monoatomic gases, helium being
especially preferred. Typically, the molar ratio of
alkene to inert gas is about ~:l to about lO:l, more
preferably about 7:l to about 9:l. The gas mixture
enters the chamber through inlet 48 at the inlet end 16
and passes downstream, in directions generally parallel
to axis 12 to the outlet 51. As exhaust system 52 and
gas supply device 36 continue to operate, the space
within vessel lO, including the interstices 92 in the
pile of closures is gradually purged of air and filled
entirely with the gas mixture at the aforementioned
subatmospheric pressure. The flow rate of the gas
mixture desirably is between about 0.2 to about 0.8
standard cubic centimeters per minute for each liter of
volume in the interior of chamber lO, (including the
volume occupied by closures).
Drive motor 2~ is actuated to rotate vessel lO
about axis 12, causing the pile 90 to continually tumble
and rearrange itself, thereby also causing new
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interstices 92 to form within the pile. At the same
time linear actuator 32 rocks frame 27, and hence
vessel 10, about pivot axis 30. This causes the
closures 80 to continually move back and forth between
S the ends of the ch~h~r, in upstream and downstream
directions parallel to the axis of the chamber. Thus,
each closure will continually travel between an upstream
region adjacent inlet end 16 and a downstream region
adjacent outlet end 14. The optimum rotational speed,
rocking movement rate and degree of rocking movement
will vary with the diameter of the vessel, the number of
closures, the type of closures and the degree of
circulating movement desired. However, for typical
conditions a rotation rate of between about 1 and
about 5 revolutions per minute; a rocking motion of
frame 26 encompassing about 20 degrees of arc and a
rocking rate of about 1 to about 3 cycles per minute are
satisfactory. Power supply 66 is actuated to apply radio
frequency excitation to coil 58 through impedance
matching network 64. This in turn applies electric
fields through the wall of vessel 10 to the gas mixture
within the vessel. The applied electric field creates a
glow discharge and forms a low-temperature plasma within
the vessel. As used herein, the term "low temperature
plasma" refers to a plasma in which the temperature of
the atoms and positively charged ions is relatively low,
and substantially below the electron temperature of the
plasma. Preferably, the temperature of the atoms and
ions in the plasma is less than about 100C and more
desirably less than about 40C and most preferably at
about room temperature~ i.e., at about 20 25C. The
temperature of the closures desirably is in the same
range. The energy applied through coil 58 tends to heat
the vessel and its contents. Cooling air supplied by
fan 54 blows over the outside of the vessel and carries
off this heat.
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The glow discharge occurs principally within
the interstices 92 in the pile of closures. As further
discussed hereinbelow, it is desirable to conduct the
process at a moderate rate. One useful indicator of the
S process rate is the degree to which the glow discharge
fills the interstices. Under normal conditions, when
the process is being conducted at the desired, moderate
rate, the glow discharge fills about one-fourth to about
three-fourths of the interstices, and most desirably
about one-half of the interstices as measured by visual
observation.
The plasma formed from the gas mixture in turn
forms polymeric coatings on the sur~aces of the
closures. The polymers consist essentially of
hydrocarbons. The polymeric coating reduces the
coefficient of friction of the closures. Coefficient of
friction can be measured and expressed in terms of a
"slip angle." As referred to herein, the slip angle is
measured by placing a closure in a generally u-shaped
track 96, seen in end view in Fig. 2, dimensioned so
that the track will guide the closures but will not bind
the closures. The track 96 is mounted on a test
fixture 98 (Fig. 3) arranged to pivot the track
gradually upwardly from a horizontal position so that
the angle A of the track with the horizontal increases
slowly. The angle A at which the closure 80, moves 2.5
cm along the track, is referred to herein as the slip
angle. The track 96 ordinarily is fabricated especially
for each type of closure. The fixture 98 may be a
coefficient of friction testing machine of the type
sold under the designation 32-25-00 by Testing Mach;n~s
Incorporated of Amityville, New York.
Typically, the uncoated closures prior to
processing have slip angles of more than about 45, and
3~ most typically more ~han about 60. The coated closures
should have a slip angle of less than 45. The precise
slip angle desired varies with the application. For
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many typical closures installed by automatic machinery,
slip angles of less than 35 may be used. The slip
angle decreases progressively as the process continues.
The rate of such decrease indicates the rate of plasma
S polymerization. This rate is principally controlled by
the power applied by the power supply 66 and is also
influenced by the flow rates and pressures in the
system. Most preferably, the process is operated at a
relatively slow rate so that the slip angle decreases
gradually, at an average rate over the entire process of
about 2 per minute or less, and most preferably
about 1.5 per minute or less. The slip angle of the
closure desirably does not decrease below about 45
until at least about 15 minutes of treatment have
lS elapsed. Preferably, the slip angle of the closures
decreases from its initial value to about 35 over a
period of about 25 minutes or more; up to about 100
minutes or more are preferred. Surprisingly, by
operating the process in this gradual manner, the
~0 leakage resistance of the closures is markedly enhanced,
vis-a-vis similar plasma coated closures made using a
more rapid polymerization process. Although the present
invention is not limited by any theory of operation, it
is believed that the gradual polymerization process
2s forms the polymeric coating with fewer cross-links
between polymer chains, and which is more flexible and
more conformable.
The following non-limiting examples illustrate
certain features of the invention:
EXAMPLE 1: A batch of 5,000 standard 20 mm size
elastomeric pharmaceutical closures of the type commonly
referred to as vial stoppers are loaded into a reactor
vessel as illustrated in FIG. 1 having an interior
diameter of about 30 cm and an axial length of about 1
meter. The vessel is rotated about its axis at about 2
rpm, but is not rocked about a pivot axis. A gas
mixture of propylene and helium is passed through the
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vessel at a flow rate of 23 st~n~rd cubic centimeters
per minute propylene and 3 standard cubic centimeters
per minutes heliumO RF excitation at 13.56 MHz is
applied. Different rates of power application are used
on different runs. A fixed 30 minute coating time is
employed for runs ~-4. A loO minute coating time is
used for run 5. The results, as shown below in Table 1,
indicate that, in runs 1-4, leakage rate increases
markedly between about 500 and 600 watts excitation.
Notably, the coated samples prepared in run 5 have a
slip angle lower than that of the coated samples from
the other runs, and have lower leakage as well.
TABLE I
RF EXCITATIOM T~ARAçE
RUN(WATTS) SLIP ANGLERELATIVE SCORE
1 400 30
2 500 29
3 600 102
4 700 127
260 30
Uncoated --- 65 10
Numerous variations and combinations of the
features discussed above can be used without departing
from the present invention as defined by the claims.
Merely by way of example, the plasma can be excited by
energy other than radio frequency energy. Microwave
excitation may be employed, using known forms of
microwave energy applicators. Also, although the
tumbling and pivoting reaction vessel discussed above is
particularly advantageous, the reaction can be conducted
in static vessels. For example, closures can be mounted
in racks for fixtures so as to maintain each closure in
a preselected orientation and assure that the coating is
applied to particular surfaces of the closure. This
approach is the most practical in the case of very large
closures. Also, the process may be performed in a
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continuous fashion along with continuous input and
output of closures from the reaction vessel where the
vessel is appropriately equipped. As these and other
variations and combinations of the features discussed
above can be utilized without departing from the present
invention as defined by the claims, the f oregoing
description of the preferred embodiment should be taken
by way of illustration rather than by way of limitation
of the claimed invention.
0 INDUSTRIAL APPLICABILITY
The present invention is applicable to
processing and use of elastomeric closures.
