Patent Grant
10751926
The invention relates to a device for reducing the microbiological impact of container products mainly made from plastic material. A plastic granulate is supplied to an extruder device, which melts the granulate. The granulate is subsequently transferred to a blow molding, filling and sealing production machine for obtaining the respective container product.
When producing plastic containers including ampule products for foods, cosmetics or for medicinal purposes, in particular ophthalmics, parenterals or for artificial feeding, the microbiological quality of the filling material is critically important. The specifications set out in the international pharmacopoeia must be satisfied. A decisive factor is the sterility of the filling material before the filling, which can be achieved for example by sterile filtration. Another decisive factor is the sterility of the inner container surfaces of the plastic container products.
In this document, “microbiological contaminants” should be understood as a collective term to refer to bacteria, spores, yeasts, fungi, viruses and endotoxins, which were previously also referred to as pyrogens in technical parlance. The technical English term also used in this regard is “bioburden”.
The prior art has already provided suggestions for minimizing or largely preventing microbiological contaminants. For example, DE 10 2008 032 635 A1 describes a food and drink industry method and device for microbiologically optimized production of blow-molded plastic containers. That known solution involves the supply during the blowing operation for the plastic container of a medium, for example in the form of air, to the inside of the corresponding premolding, at a temperature of between 80° C. and 140° C. The heated air serves as a sterilization for the killing of bacteria. In order for this method to be effective, in view of the relatively low treatment temperatures, very long treatment times are required, certainly in the region of several hours, in order to sustainably prevent a build-up of bacteria.
DE 10 2011 008 132 A1 describes a method and a device for the production of blow-molded, at least partially sterile containers, in which a premolding made of a thermoplastic material is initially heated and is then stretched by a stretching rod and has a pressurized fluid applied to it. A sterilizing agent is additionally supplied in the region of the premolding. The known method preferably uses as a sterilization agent vaporized hydrogen peroxide, which is mixed with hot air, with the hydrogen peroxide concentration being approximately 15 to 35 percent by weight. The breakdown products of such chemical sterilization agents can contaminate the filling material and can have harmful toxicological consequences.
DE 695 20 445 T2 discloses a method and an associated device for the sterile packaging of a drink, in which, as part of the blow molding step for the container, the container is heated to a temperature sufficient to sterilize the inside of the container. Because a reliable sterilization requires temperatures significantly higher than 200° C. for a time period of several minutes, the choice of plastics for the container material for this known method is correspondingly limited. The polymers preferably used for the packaging of pharmaceuticals, such as polyethylene or polypropylene, can then not be used at all due to their low working or melting temperatures.
DE 10 2008 006 073 A1 discloses a so-called blow molding, filling and sealing production machine, which is particularly suitable for the production of filled containers for medicinal purposes. These containers include ampules as container products for eye drops with filling volumes of for example 0.1 ml to 10 ml, as well as ampules for injection solutions in the range of typically 0.5 ml to 50 ml. Standard clock speeds for the production of such filled and sealed blow molding, filling and sealing (BFS) containers are in the range of 10 to 18 seconds, whereas in modern systems of the type disclosed in DE 10 2008 006 073 A1 however, the cycle time is just 2 to 4 seconds. Due to these low cycle times alone, the use of the above-mentioned known sterilization methods is ruled out, which methods cannot be used for BFS methods because the container molding is immediately followed within a few seconds by the filling and a premolding or even an empty container is not available for a sterilization operation.
The microbiological status of containers produced according to the BFS method is described in the article by Frank Leo et al. “Evaluation of Blow-Fill-Seal Extrusion through Processing Polymer Contaminated with Bacterial Spores and Endotoxin”, published in the PDA Journal of Pharmaceutical Science and Technology Vol. 58, No. 3, May-June 2004, pages 147 to 158 for the particular case of a BFS system of type 624 by the company Weiler Engineering with cycle speeds of 12 to 18 seconds (see page 148). Amongst other things, the specialist article discloses that reduction of spores occurs by two possible mechanisms, either thermal deactivation resulting from the long-term influence of heat during production (see page 153, bottom left) or as a result of the achieved homogeneous distribution (see page 153, 5th paragraph) of the spores in the molten mass and an associated possible thermal inactivation. In spite of this achieved homogeneous distribution and the long residence time, the authors report only a small bacteria count reduction in the region of only 102 to 104 colony-forming units per gram (CFU/g).
The results described above are, as the authors explicitly state, not transferable to other systems, in particular not to those BFS systems with significantly lower residence times at a raised temperature, for example in the form of systems made by the company rommelag of type 460, which are the subject of the technical teaching according to DE 10 2008 006 073 A1. The clock speeds in those systems, as stated above, are typically in the region of less than 5 seconds. In these systems, no cutting of the warm polymer tube occurs, and the filling occurs by sterile filling tubes inside the intact plasticized polymer hose. The hose in any case then constitutes a sterile barrier relative to the exterior space or the environment.
Unfortunately it is not, however, always possible to ensure that the polymer granulate used for the BFS process has a sufficiently minimal microbiological contamination. It is then in practice possible, to some extent also as a result of incorrect transport, storage and handling of the plastic granulate, for microbiological contaminants, for example in the form of spores, to reach the granulate surface. The contaminants reaching the granulate surface can lead to an undesirably high microbiological contamination, which is not always reduced to an adequate extent by the previous BFS method according to the prior art.
Given this prior art, the problem addressed by the invention is to provide an improved device that may be integrated of BFS production processes and that helps to significantly deactivate the microbioloical contaminants.
This problem is solved by a device and a hose head in accordance with the invention.
According to the invention, a guide device has a flow guide for the melted plastic material such that the microbiologically contaminated plastic material regions of the surfaces are guided into the inside of the polymer hose or polymer strand. Contaminants of less contaminated plastic material regions of the then fully produced plastic container product are then surrounded on all sides. Any microbiological contaminants present, such as spores, bacteria, endotoxins, etc., are reliably enclosed by uncontaminated plastic material so that they can no longer compromise the microbiological status of the container content, or its sterility. This knowledge for the purpose of obtaining a reliable enclosure of undesirable microbiologically-effective contaminants, i.e. using an intentional non-homogeneous distribution of biological particles in the polymer, is not identifiable in the prior art and is surprising to the average person skilled in the art of production of plastic container products.
The device according to the invention is advantageous in that, as specified, the starting material plastic granulate is microbiologically contaminated only on its surface. Microbiological contaminants are then guided to the inside of the plastic hose and then to the inside of a container wall and are then inactivated.
In particular, in a surprising manner, bacterial spores specifically can be significantly inactivated through the use of special, mostly distributively mixing additive elements in the extruder or the extruder device mainly by this encapsulation mechanism. The installation of such a static melt mixer takes place without the use of additional mobile parts, preferably between the extruder device and a hose head, which discharges a closed plastic shell surface, which later forms the container wall of the container products.
The use of such static mixers in the described BFS method has been avoided by specialists in the past because the static mixers are necessarily associated with a pressure drop. The pressure drop necessitates a more pressure-resistant design of the extrusion system and significantly increases the energy requirement during operation of the machine. Mixing elements are typically used only to obtain a uniform, homogeneous distribution of dyes, fillers, reinforcing fibers, etc. that are added to the polymer.
Although said static mixing elements—unlike dynamic mixers—do not significantly change the temperature of the polymer used and it is then possible to rule out a thermal effect (heat sterilization effect) of the mixer on the bacteria count reduction, a significant spore inactivation occurs as a result of the encapsulating enclosure of the spore material by uncontaminated plastic, in other words, an advantageous non-homogeneous distribution of microbiological contaminants over the cross section of a melt strand and, resulting therefrom in a surprising manner, an advantageous non-homogeneous distribution of microbiological contaminants over the cross section of a container wall. There is no equivalent of this in the prior art.
An additional device according to the invention for reducing microbiological contaminants involves a special flow guide of the melted polymer immediately before discharge from the nozzle of a hose head. The hose head is immediately upstream of the blow molding, filling and sealing production machine.
For the BFS method, tools are usually used for the hose head within the realm of easily constructed annular groove distributors, spiral mandrel distributors, spider distributors, screen basket distributors or perforated plate distributors. Such distributors are described in detail in the book by Walter Michaeli: Extrusionswerkzeuge für Kunststoffe und Kautschuk; Bauarten, Gestaltung und Berechnungsmöglichkeiten [Extrusion Tools for Plastics and Rubber; Construction, Design and Calculation Methods], Carl Hanser Verlag, 2009.
By contrast with these known distributor tools, the invention advantageously uses a hose discharge head with an oval cross section, having an oval housing and an oval sleeve, with two inputs occurring simultaneously and symmetrically along the discharge oval.
Compared with other standard distributors, the flow guide of the plasticized polymer in the hose head according to the invention results in a very narrow residence time range of the molten polymer along the circumference of the hose to be produced. Due to this consistent residence time of the polymer and the flow in the thin, flat distributor channels, as a component of the flow guide according to the invention in the context of the guide device, an advantageous non-homogeneous alignment of microbiological contaminants into the inside of the polymer hose is obtained. Improved bacteria inactivation is then a result of plastic material that hermetically encloses microbiological contaminants and prevents contact of the contaminants with the filling material, but also with the outer surface of the container.
Other objects, advantages and salient features of the present invention will become apparent from the following detailed description, which, taken in conjunction with the drawings, discloses a preferred embodiment of the present invention.
Referring to the drawings that form a part of this disclosure and that are schematic and not to scale:
a, b, c are a top view, a front view in section, and a side view in section, respectively, of the hose head according to
As can also be seen from
To assist with the removal of the containers 11 and thus of the container chain 9 from the walls of the individual molding parts 7 that move apart from one another at the discharge region, the demolding device 3 conveys a displacement movement to the container chain 9, as indicated in
This blow molding, filling and sealing machine 1 together with the demolding device 3 according to
The working temperature of polyethylene as the plastic material used is about 170° C. to 200° C. and is about 180° C. to 250° C. in the case of polypropylene materials. The discharge pressure behind the extruder device 19 with the mixer device 31 at the point of transition to the hose head 33 conventionally is approximately 100 to 400 bar.
According to the invention, the extruder device has in the context of the mixer device 31 a guide device 35, which permits flow guidance for the molten plastic material in such a way that the potentially present microbiological contaminants migrate to the inside of the plastic strand 37. The microbiological contaminants are then enclosed by less contaminated plastic material regions 39. The mostly distributively mixing parts of the respective mixer device 31 form statically designed melt mixers, with a channel guide 41. Channel guide 41 distributes plastic content contaminated with biological contaminants such as spores, bacteria or endotoxins, etc., by the extruder device 19 in a non-homogeneous manner in the produced plastic strand 43, which leads in a surprising manner to contaminants also in the polymer hose and thus in the wall (
As static mixer devices 31, mixing elements without mobile parts for example are used, of the kind that can be procured with the type designations SMX™ and SMX™ plus from the company Sulzer Chemtec AG, Winterthur, Switzerland. SMB plus melt mixers from the company Prom ix Solutions, Linden, Germany or the melt mixer CSE-X from the company Fluitec, Neftenbach, Switzerland, are likewise suitable for this purpose. Furthermore, such static mixing devices can be used on the basis of their technical construction as described in the U.S. Pat. No. 7,077,561 B2 and in the U.S. Patent Publication No. 2012/0106290 A1.
According to the invention, these static mixer devices 31 demonstrate achievement of the desired inherently non-homogeneous distribution of microbiological contaminants, although these mixers are actually used for the homogenization of polymer melts, in particular when dyes, filling materials, etc. are added.
In a surprising manner it was thus found that static mixers that are known per se demonstrate a completely different mixing behavior: while dyes, filling materials, reinforcing fibers, etc. and similar particles are homogeneously distributed in the container wall—as is always necessary for dyes for optical reasons—, in the case of microbiological contaminants, with the non-homogeneous distribution that is advantageous according to the invention, the described encapsulating effect is obtained.
As already explained, in a surprising manner the advantageous non-homogeneous distribution of the solid plastic melt strand 43 is advantageously maintained even in the case of forming of the polymer hose and then in the cross section (
The reason for this is not known, but it is suspected that this non-homogenous distribution is due to a complex interaction of several factors. On the one hand, this distribution involves the surface chemistry and structure of the microbiological contaminants, probably in particular their physical wettability and chemical interactions with hot polymer melts. On the other hand, their size and form factors, which influence the alignment of the microbiological contaminants in the melt flow. It should be taken into account that the rheological properties of the polymer are highly dependent on the temperature, the shear forces and the molecular weight distribution of the polymers themselves, and thus their distribution across the strand cross section or hose cross section.
The previously described guide device for the plastic strand 43 can, additionally or alternatively to the respective mixer device 31, comprise the hose head 33 in the production line before the production machine 1 with an oval-like cross section for the plastic material discharge to the molding tools 7 of the production machine 1. This discharge cross section 45 is formed in the manner of a slit (cf.
As
The two respective supply lines 56 as part of each guide track/distributor channel 55 with the involvement of the top feed point 59 and towards all sides, starting from the corresponding discharge plane, permit the supply of the slit-shaped discharge cross section 45 at the bottom side of the hose head housing 53. According to the depiction of
The guide tracks 55 in the hose head 33 delimit at the external circumference receptacles 69, which can be penetrated by filling pins (not depicted) of the production machine 1. The blow-molded plastic containers can then be filled in a sterile manner with a filling medium. Thanks to the consistent residence time of the polymer for the container wall and the through-flow in the thin-faced distributor channels that form the slit-like discharge section 45, there is a non-homogeneous alignment of the microbiological contaminants to the inside of the formed polymer hose, which is supplied, viewed in the viewing direction of
In the context of practical testing of the device solution according to the invention, for all of the exemplary embodiment materials, container sizes and machine settings were selected that represent the worst case regarding the mechanism of reduction of microbiological contaminants. As an example of microbiological contaminants, resistant spores of Bacillus atrophaeus and Bacillus pumilus were selected as test bacteria, as is standard in sterility testing. As container materials, polymers that have low BFS working temperatures were additionally used in order to keep at low levels the thermal effects on the artificially added spores. In addition, process parameters were selected which have only minimal effects on the spores, but which lead to container products with useable quality and standard output quantities. The throughput of polymer through the extruder device 19 was thus set to the upper limit in order to minimize the duration of the heat effect on the artificially added spores.
Furthermore, a BFS system of the type 460 from the company rommelag, Waiblingen, Germany, was used, as is partially depicted in
To produce the contaminated granulate tests endosphores of Bacillus atrophaeus ATTC 9372 with a D-value D160° C.=0.285±0.08 min were used. In a similar manner, spores of the very small reference bacteria, Bacillus subtilis 1031, were used. The spores were uniformly distributed on the plastic granulate used and the spore content was verified under laboratory conditions. The concentration range was 103 to 106 CFU per gram. 10 ml containers 11 filled with 6 ml liquid CASO nutrient solution were also produced.
For further clarification: CASO nutrient solution is a complex medium, to which is added, besides glucose, peptone obtained proteolytically from milk protein (casein peptone) and peptone obtained proteolytically from soy flour (soy flour peptone). Casein peptone is rich in free amino acids and the soy flour peptone is distinguished by a high carbohydrate and vitamin content. Such nutrient media are particularly well suited for cultivation of fastidious microorganisms.
For each test batch more than 12,000 container products were produced, with the analytical procedure otherwise corresponding to the content of the above-mentioned article by Frank Leo et al. “Evaluation of Blow-Fill-Seal-extrusion through Processing Polymer Contaminated with Bacterial Spores and Endotoxin”.
In a first step, three reference batches, i.e. without application of the methods according to the invention, were prepared for the spore inactivation. For this purpose, a pin wrench distributor with holes, which is standard in extrusion technology, was used as a dynamic mixer device (as shown in the book by W. Michaeli), and a hose head with a circular cross section and a circular cylindrical sleeve was used, with a bacteria count reduction being obtained, in particular due to thermal effects, of on average 103 CFU/gram (colony-forming units per gram).
When the polymer granulate contaminated with spores of the Bacillus atrophaeus is extruded using the above described static mixer devices 31, with the total length of the extruder device 19 remaining unchanged compared with the reference tests, a deactivation of the contaminant through the encapsulation was obtained that was improved by a factor of 50-170. In the case of the use of spores of the Bacillus subtilis, an increased effect compared with the reference was obtained with an inactivation factor of on average 100.
When, in an additional or alternative manner, the contaminated polymer granulate is introduced with a hose head 33 with an oval sleeve 67 in accordance with the design according to
All of the above-mentioned methods according to the invention together with the device according to the invention for minimizing the microbiological contamination have the advantage that it is not an empty container or even an already filled container 11 that is to be sterilized, as is described in the prior art. Instead, solely the already plasticized polymer suffices as a mechanism of inactivation by encapsulation. There is no equivalent of this in the prior art.
When producing multilayer containers according to the BFS method, as described for example in DE 103 47 908 A1, it may be sufficient to use the respective described devices according to the invention solely for the polymer granulate which forms the inner surface of the container 11.
While one embodiment has been chosen to illustrate the invention, it will be understood by those skilled in the art that various changes and modifications can be made therein without departing from the scope of the invention as defined in the claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2015 012 937 | Oct 2015 | DE | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2016/001511 | 9/7/2016 | WO | 00 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2017/054903 | 4/6/2017 | WO | A |
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| Number | Date | Country | |
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| 20180281266 A1 | Oct 2018 | US |
