Note: Descriptions are shown in the official language in which they were submitted.
1
73182
Boehringer Ingelheim Pharma KG Case 5/1263-Ro
D-55216 Ingelheim/Rhein Foreign filing text
Process and apparatus for producing pellets
The invention relates to a process for producing
pellets from a viscous medium and an apparatus for
carrying out this process.
In drug therapy, pellets are frequently used as
carriers for pharmaceutical substances; they are prepared
by various methods, some of which are very laborious.
According to one of these methods, the so-called spray
hardening method, a liquid medium enriched with the
pharmaceutical substances is continuously forced through
a spray nozzle. On leaving the spray nozzle, the jet of
liquid is broken up into particles of different sizes
which harden as they fall.
Uniform pellets, i.e. those of identical size, which
have reproducible and predictable release
characteristics, cannot be produced by this method,
however, but instead the particles obtained in a broad
spectrum of sizes have to be sorted by screening in a
subsequent operation. Apart from the fact that sometimes
a large proportion of the medium being processed has to
be rejected, in order to produce pellets of other sizes
it is necessary to change the nozzle and subsequently
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grade the pellets. The work involved in manufacture,
even with this simple spray hardening process, is
therefore considerable.
The aim of the invention is therefore to provide a
process for producing pellets from a viscous medium and
an apparatus for carrying out this process which make it
possible always to produce uniform pellets of virtually
the same size and reproducibility, which will therefore
have the same release characteristics, in a single
operation. Moreover, it should be possible to vary the
size of the pellets by simple means and to process media
of differing viscosity. The labour involved in achieving
this should be kept to a minimum but at the same time the
pellets should be capable of being produced cheaply
within a short space of time.
According to the invention, the process by which
this is to be achieved is characterised in that the
medium which is to be processed is supplied continuously,
under preferably constant pressure, to a metering device
which can be operated cyclically, by means of which the
medium is divided into individual fragments of a given
length and these are ejected over a pre-selected
distance.
It is useful to adjust the temperature of the medium
being processed before it is fed into the metering device
by heating or cooling a storage container and/or a
delivery line and/or the metering device and to adjust
the temperature of the ejected fragments during the
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ejection over the entire area or in one or more sections
of a distance by means of the ambient temperature.
The individual fragments can also be ejected at high
speed,by means of a discharge device, in which the
fragments are expelled in a ballistic trajectory and can
be provided with a coating during the ejection.
The apparatus for carrying out this process is
characterised by a metering device which can be operated
cyclically, to which the medium to be processed can be
supplied continuously under pressure and by means of
which the medium can be divided up into individual
fragments of a given size which can preferably be ejected
at high speed and over a pre-selected distance.
The metering device may be constructed as a shutoff
valve which is operated cyclically by magnetic,
hydraulic, pneumatic, piezoelectronic or mechanical
means, while the valve member of the shutoff valve may be
constructed as a sphere or cone co-operating with a
spherically shaped valve surface or as a slide which can
be pushed into the delivery line, provided with a tip
which is triangular in cross section.
However, the metering device may also be constructed
as a fluidic valve constructed in the form of a section
of hose attached to the delivery line and provided with a
piezo-actuated drive element.
According to another embodiment, the metering device
may also be constructed as a valve tappet which is
displaceably inserted in a housing and is cyclically
operated by magnetic, hydraulic, pneumatic, piezo-
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electronic or mechanical means, which has a conical or
spherical tip and co-operates with a collecting chamber
to which the medium can be fed from a storage container
preferably integrated in the housing.
It is appropriate to associate with the valve tappet
a conically shaped chamber adapted to fit its tip and to
incorporate the chamber as well as an outlet port
adjoining said chamber in a cover which is releasably
connected to the housing.
In order to ensure a uniform supply of the medium
which is to be processed, the collecting chamber is to be
formed by two or more supply channels extending radially
to the chamber associated with the valve tappet,
preferably incorporated in the cover, these channels
being connected to the storage container directly via an
annular space or via connecting channels.
Moreover, the storage container and/or the housing
should be fitted with heating cartridges in the region of
the collecting chamber and in order to drive the valve
tappet a piston should be provided which is mounted in a
guide bushing replaceably inserted in the housing.
It is also advantageous to provide, downstream of
the metering device, a discharge device which can be
supplied with a carrier medium, e.g. compressed air, to
accelerate the fragments which are to be expelled.
Experience has shown that there is a possibility of
the discharge device becoming blocked. To counter the
risk of blockage, an oscillator may advantageously be
included in the apparatus. This oscillator is directly
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connected to the discharge device and generates a
vibration of 20 Hz to 20 kHz, depending on the type of
fouling which is transferred to the discharge device.
This vibration is produced in the oscillator by means of
a generator. As a result of this oscillating effect, no
medium for processing is left on the opening and the
product drips off cleanly.
The outlet port of the metering device or of the
discharge device should be inclined upward at an angle a
of 25 to 35° to the horizontal, in order to achieve a
ballistic trajectory.
It is also advisable to provide, downstream of the
metering device or the discharge device, a tunnel
equipped with cooling elements and/or having a gas
atmosphere, which is supposed to have an operating
pressure below or above atmospheric pressure and which
may be fitted with one or more spray nozzles for coating
the fragments or pellets. In addition, a catching
container may be provided downstream of the metering
device or the discharge device.
Moreover, the medium which is to be processed should
be enclosed in a heatable or coolable storage container.
The metering device, preferably together with the drive
members and optionally the discharge device, may be
arranged together in one housing.
Using the process according to the invention or the
apparatus for carrying out this process, it is extremely
easy and cheap to produce pellets of virtually identical
size and hence with constant reproducibility, as carriers
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of pharmaceutical substances, from a viscous medium and
to change their size without any difficulty, if required.
Using the metering device, in fact, the medium which is
continuously supplied under pressure can be divided into
individual fragments the length of which can be adjusted
to suit the intended use, and these fragments can be
ejected at high speed so that the fragments are shaped
into pellets during their flight as a result of the
surface tension present, these pellets taking on the same
shape as one another, since the fragments supplied have
the same shape and the conditions of ejection of the
fragments are also the same. There is therefore no need
to grade them; nor is there any reject material.
Since all the pellets produced in one step of the
process therefore have virtually the same shape and
surface, the release characteristics of the particular
group of pellets will be reproducibly uniform and
predictable. Moreover, during manufacture, the size of
the pellets produced can readily be controlled using the
metering apparatus, since the metering apparatus can
easily be made to open and close cyclically and
individual sizes of pellet can readily be produced by
varying the opening and closing times. Thus, by
connecting a plurality of control mechanisms with
correspondingly high cycle rates in parallel,
pharmaceutical formulations can be produced extremely
economically by manufacturing pellets with a homogeneous
particle profile.
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The drawings show two embodiments of an apparatus
constructed according to the invention for producing
pellets from a viscous medium, which will be described
more fully hereinafter. In the drawings, which are
diagrammatic:
Figure 1 shows a block circuit diagram of an
apparatus provided with a metering device,
Figure 2 shows the apparatus of Figure 1 with a
discharge device connected downstream,
Figure 3 shows the apparatus of Figure 1 in a
modified embodiment,
Figure 4 shows the metering device of the apparatus
according to Figure 3 on a larger scale,
Figures 5 and 6 show different embodiments of the
metering device which may be used in the apparatus of
Figure 1,
Figure 7 shows a tunnel which may be used in the
apparatus of Figure 1,
Figure 8 shows a different embodiment of an
apparatus for producing pellets, in axial section,
Figure 9 shows the apparatus according to Figure 8,
in side elevation,
Figure 10 shows a detail of Figure 8 on a larger
scale, and
Figure 11 shows the metering device according to
Figure 4 but with an oscillator which prevents blockage
of the discharge device.
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The apparatus shown in Figures 1 to 3 and 8 and 9
and designated 1 and 51 is used to produce pellets 4 of
identical shape from a viscous material 2 which is stored
in a storage container 5 in the apparatus 1 and fed
continuously, under pressure, through a delivery line 6
equipped with a pump 7. In order to convert the flow of
medium 2 into the pellets 4, the apparatus 1 is provided
with a metering device 11 in which the medium 4 is
divided into individual fragments 3 of equal length from
which the fragments 3 are ejected into a catching
container 10 over a given distance S. The metering
device 11 is disposed in a housing 8.
In the apparatus 1 according to Figure 1 the
metering device 11 is formed by a shutoff valve 12 which
can be operated electrically, hydraulically,
pneumatically, piezoelectrically or mechanically by means
of a drive member 13. The shutoff valve 12 may be
formed, as shown in Figures 4, 5 and 6, by a ball 14 or
by a cone 15, as shown by a dotted line in Figure 4, as a
movable valve member which co-operates with a spherically
shaped valve seat 16, or by a slide member 17 engaging
with its conical tip 18 in the delivery line 6.
According to Figure 6, the metering device is
constructed as a fluidic member in the form of a hose
section 19 connected to the delivery line 6 and
surrounded by a piezo-actuated drive element 20. The
medium 2 is again divided into fragments by the pressure
acting on the hose section 19 from outside.
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According to Figure 2, downstream of the metering
device 11 is a discharge device 21 which is connected to
the metering device 11 via an intermediate line 9. By
means of the discharge device 11 the fragments 3 are
ejected at high speed. To achieve this, a carrier
medium, e.g. compressed air, is supplied to the discharge
device 21 through a line 22 and acts on the fragments 3
which are to be ejected.
According to Figure 11, downstream of the metering
device 11 is a discharge device 21 which is connected to
the metering device 11 via an intermediate line 9. The
oscillator 40 is connected directly to the-discharge
device 21. The generator 41 sets the oscillator 40
vibrating. This oscillating system helps prevent
blockage of the nozzle.
Downstream of the discharge device 21, according to
Figure 7, is a tunnel 31 in which the expelled fragments
3 can be cooled down by means of a gas atmosphere 35. In
addition, the tunnel 31 may be fitted with spray nozzles
36 by means of which an active substance 37 can be
sprayed, for example, in order to coat the fragments 3
and/or pellets 4.
As shown in Figure 3, the storage container 5 may
optionally be fitted with heating elements 32 to increase
the viscosity of the medium 2 stored therein. For the
same purpose, the metering device 11 may be kept at a
constant operating temperature by means of heating
elements 33. There are also cooling elements 34 in the
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tunnel 31 according to Figure 3, for cooling the pellets
4.
The pellets 4 are produced by means of the apparatus
1 as follows: the medium 2 which is continuously fed into
the metering device 11 by means of the pump 7 at a
constant pressure is divided into individual fragments 3
by the shutoff valve 12 which opens and closes
cyclically; by varying the opening and closing times of
the shutoff valve 12 the length of the fragments 3 can be
adjusted individually.
Closing the shutoff valve 12 causes the valve member
to accelerate the fragments 3 additionally and eject them
faster, directly or by means of the discharge device 21.
In their flight over the distance S adjacent to this
discharge device 21 the individual fragments 3 are
deformed as a result of surface tension, as shown in
Figure 7, to form spherical pellets 4 which are virtually
identical in size and reproducibility.
In the apparatus 51 for producing pellets shown in
Figures 8 to 10, the metering device 61 is formed by a
valve tappet 62 provided with a conically shaped tip 63
which co-operates with a suitably shaped chamber 57. The
valve tappet 62 is movably inserted in a housing 52 which
contains a storage container 54 for the medium which is
to be processed and guide channels 55 and 55' through
which the medium can be fed via an annular space 66 into
a collecting chamber 65 associated with the valve tappet
62.
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In the embodiment shown, the collecting chamber 65
is formed by three radially directed channels 67 which
are connected to the annular space 66 and open into the
chamber 57 which is bounded by a counter-surface 59
associated with the valve tappet 62.
The channels 67 and also the chamber 57 are
incorporated in a cover screwed onto the housing 52.
Also, an outlet port 58 through which the fragments can
be expelled individually is provided in the cover on an
extension of the chamber 57.
The valve tappet 62 is driven by a cyclically
operated piston 64 which is displaceably mounted in a
bushing 53 inserted in the housing 52. Its passage
through the housing 52 is sealed off by a membrane 68
through which the valve tappet 62 passes. Also, in order
that the medium can be processed at any selected
operating temperature, a plurality of heating cartridges
69 or 70 are inserted in the housing 52 in the region of
the storage container 54 and valve tappet 62.
The medium located in the storage container 54 is
acted upon by pressurised gas via a connection 60, so
that the medium is forced through the channels 55, 55',
the annular space 66 and the channels 67 forming the
collecting chamber 65 into the chamber 57. If the valve
tappet 62 is driven cyclically by means of the piston 64,
at each stroke a fragment corresponding to the capacity
of the chamber 57 is forced out of the discharge port 58
and is then automatically shaped into a pellet.
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