EP2030699A1 - Method for washing smaller objects - Google Patents

Abstract

The method involves bringing articles (6) in contact with washing liquid (20) i.e. hot water, in a closed container (2) in order to remove impurities from a surface of the articles. Pressure in the container is lowered to a value of less than 600 millibar above a fluid level of the washing liquid, where the articles are covered by the washing liquid in the container, and alternatively increased when the pre-determined low pressure is reached in the container or when no pressure reduction is observed in the container. An air is sucked off with a vacuum pump (14).

Description

The invention relates to a method for washing smaller objects, in particular closure plugs or other closures for pharmaceutical purposes, in which the objects are brought into contact with an aqueous washing liquid in a closed container in order to remove impurities from the surface of the objects.

From the EP 1 449 543 A1 the applicant are a method and an apparatus of the type mentioned for cleaning and sterilization of smaller items, such as plugs of infusion bottles or vials, known where the items in a treatment container with hot water or a water-air mixture, optionally with the addition of Detergents are rinsed to eliminate impurities or foreign bodies, if any, and remove with the washing liquid from the container.

Next is from the DE 299 23 723 U1 a cleaning and sterilizing machine for smaller items known, such as closure elements of pharmaceutical vessels, with which the objects are treated in a treatment tank first with water, steam, hot air and then possibly for siliconizing with a silicone dispersion. The dispersion is forced out of the container by the supply of compressed air and drained, before the small articles are dried in a hot air stream by introducing sterile filtered and heated compressed air on one side into the container and sucked by applying a vacuum on the other side.

A similar method for cleaning and sterilizing small objects is in DE 44 09 659 A1 disclosed.

The known methods are quite well suited for the depletion of particulate contaminants from the surfaces of the objects, if all surfaces are readily accessible to the washing or rinsing liquid, so that they are slightly wetted by the liquid, which is a prerequisite for a detachment of adhering contaminants. However, this is not always the case, especially with smaller sealing plugs made of rubber or the like, since these plugs frequently have a recess in their plug part projecting into the interior of the pharmaceutical vessels, which sometimes has a considerable depth but only a relatively small diameter. In such plugs, the air contained in the interior of the recess escapes, inter alia due to the high surface tension of the aqueous washing liquid or only incomplete from the recess when the objects are flooded in the container with the washing liquid. The remaining in the recesses air bubbles thus prevent wetting of the surfaces with the washing liquid, so there is no depletion of impurities.

For this reason, detergents or other surfactants (surfactants) are often added to the washing liquid in order to counteract the formation of air bubbles in the recesses by reducing the surface tension of the washing liquid and to improve the wetting of their surfaces. However, in this case, contamination of the surfaces of the articles with residues of these detergents or surfactants can not be excluded.

Although it is also possible to destroy the air bubbles by moving the container with the washing liquid and the objects for a long time in motion to produce turbulent flows at the interfaces between the objects and the washing liquid. However, these currents often do not reach into the interior of the recesses, while on the other hand unwanted increased abrasion of the objects is observed.

As the particulate impurities adhering to the articles may also include, but are not limited to, endotoxins, i. Ingredients of outer cell membranes of Gram-negative bacteria, which are already present in lowest concentrations, e.g. As pyrogens are biologically active, an entry of such substances into the interior of vessels for pharmaceutical purposes must be safely prevented, especially since endotoxins, in contrast to the bacteria from which they are derived, are very stable to heat and therefore survive even a sterilization. On the other hand, endotoxins can be detected very well even at low concentrations, so that the depletion of endotoxins from sealing plugs for pharmaceutical purposes in the course of a washing process is well suited for assessing the quality of the washing process.

Proceeding from this, the present invention seeks to improve a method of the type mentioned in that impurities such as particles and endotoxins, even inside relatively deep and narrow recesses are well cleaned, without the addition of surfactants and / or a strong relative movement between the objects and the washing liquid is required.

This object is achieved in that the pressure in the container is alternately lowered and increased with the objects covered by the washing liquid. Appropriately, the pressure is lowered first and then increased. Preferably, the process of alternating pressure reduction and pressure increase is carried out several times by the container is first several times successively first applied to a negative pressure and then with an overpressure.

By the combination of features according to the invention, it is possible, adhering to the surface of the objects air bubbles themselves to remove from relatively deep and narrow recesses and so to ensure complete wetting of the surface of the objects with washing liquid, which is a prerequisite for a purification of impurities, such as particles and endotoxins.

The success of the method according to the invention is based on the volume change of the air bubbles or on a collapse of the air bubbles due to the change in pressure in the container. When the pressure in the container is lowered, the air bubbles expand, causing some of the air contained therein to escape from the recesses as a result of the increase in volume and to rise in the washing liquid as a result of the volume increase causing the skin of the air bubbles and the air bubbles to rupture Collapse and divide into several separate smaller bubbles. In addition, the pressure reduction leads to a degassing of the washing liquid. In a subsequent increase in the pressure in the container, the former has the consequence that the air remaining in the recesses occupies a significantly lower bubble volume and therefore the contact area between the air bubbles and the surface of the objects is smaller or the surface wetted by the washing liquid becomes larger. The latter causes in a subsequent increase in pressure that air or components thereof diffuse from the air bubbles in the washing liquid and dissolve in the washing liquid, which in particular small air bubbles are completely eliminated. If the pressure increase abruptly, it also leads to a slump of washing liquid in the air bubbles and thus their collapse. In a subsequent lowering of the pressure in the container, remaining air bubbles expand again, collapse again and divide. Often, only part of the bubbles stick to the surface of the objects. The remaining bubbles rise to the surface of the washing liquid, where the air contained in them is sucked by means of a negative pressure generating vacuum pump.

In order to ensure that at least part of the air bubbles adhering to the surfaces of the objects collapse by breaking washing liquid into the air bubbles when the pressure in the container is lowered, the pressure in the container is lowered to a value of less than 600 mbar, preferably to a value less than 300 mbar, and most preferably less than 100 mbar. As a result, the bubble volume increases by a multiple, resulting in several times in succession to the collapse of the bubbles and the escape of a portion of the air contained therein.

A preferred embodiment of the invention provides to supply warmed in the container heated liquid and to reduce the pressure in the container to below the boiling point of the washing liquid, which in turn is higher, the higher the temperature of the supplied into the container washing liquid. When the pressure falls below the boiling point of the washing liquid, it evaporates, whereby vaporous washing liquid penetrates into the bubbles at the phase boundary with the air bubbles. This leads to a further increase in the bubble volume and thus promotes a collapse of the bubbles or their detachment from the surface of the objects, similar to the case of steam bubbles in boiling water, which reaches a certain size of the surface of a hot pot bottom or a Release heating coil. The heat of evaporation is removed from the washing liquid, which cools as a result.

The lowering of the pressure in the container preferably takes place in that above a liquid level of the washing liquid in the container air is sucked out of the container, preferably by means of a vacuum pump.

In order to provide a substantial reduction in bubble size upon subsequent increase in pressure in the container, the pressure is increased, according to a preferred embodiment of the invention, at least five times, preferably ten times, and more preferably twenty times, that of the pressure Lowering the pressure in the container prevails. In addition, the pressure increase is made impact or pulse, because this also leads to a collapse of water through the skin of the air bubbles in the recesses and thus to a collapse of the bubbles and to escape of air from the recesses. The achieved in this way reduction of the bubble volume and thus the contact surface of the air bubbles has a wetting of other surface areas of the objects result. Preferably, the pressure in the container is increased at least to atmospheric pressure, better up to more than 1500 mbar, and most preferably to a value of about 2000 mbar.

In order to remove all air bubbles and to wet the entire surface of the objects, the alternate lowering and increasing the pressure in the container is advantageously carried out several times in succession.

According to a further preferred embodiment of the invention, a negative pressure is applied to the container before the supply of the washing liquid into the container, which is preferably maintained during the supply of the washing liquid. After the container has been filled, therefore, a very low pressure already prevails in the interior of the bubbles which have formed in the recesses of the objects, so that, in the event of a subsequent abrupt increase in pressure, this leads to the breakthrough of washing liquid already described above in the bubbles which leads to a collapse of the same and a division into smaller bubbles.

The lowering of the pressure in the container is preferably carried out by means of a vacuum pump connected to the container by air is sucked from the container above the liquid level of the washing liquid, while for increasing the pressure sterile compressed air is advantageously supplied into the container. Both approaches allow to accurately control the pressure in the container.

In order to ensure a complete covering of the objects contained in the container with the washing liquid and to limit the amount of air to be sucked from the container or to be supplied to the compressed air and the time required for these operations, the container is preferably substantially completely with the Washing liquid filled.

In order to turn plugs whose recess faces downwards so that the air can escape completely from the recess, the container can be moved during the repeated lowering and increasing of the pressure, preferably by reversing it one or more times after each pressure change cycle. However, it is also possible to pivot the container during the pressure reduction and / or during the pressure increase, but a submergence of the junction of the leading to the vacuum pump or compressed air source line should be avoided so that no water sucked or no air bubbles in the washing liquid be generated.

The washing liquid is suitably made of pure water to which no detergents or other surface-active substances are added for wetting the surfaces and for removing bubbles. However, for other reasons, it may be necessary to use detergents or other surfactants at least during a washing or rinsing operation.

A further preferred embodiment of the invention provides that the objects are supplied to the container before the supply of the washing liquid, and that then applied a negative pressure to the container and steam, preferably saturated steam, is fed into the container. The supplied vapor condenses on the surfaces of the objects and wets them with water in the form of small water droplets. Since these water droplets easily combine with the subsequent supply of the washing liquid into the container with the washing liquid and beyond an adhesion of air bubbles on the surfaces of the Counteracting objects, a complete wetting of the surface is facilitated with the washing liquid.

In the following the invention will be explained in more detail with reference to an embodiment shown in the drawing, wherein the FIGS. 1 to 7 show schematic views of a filled with a washing liquid container with a single, covered by washing liquid stopper during a lowering and an increase in the pressure in the container.

For cleaning and sterilizing rubber stoppers for pharmaceutical containers, such as infusion bottles or vials, the stoppers are filled into a container, such as one in the EP 1 510 227 A1 the applicant described in more detail treatment and transport container in the one mentioned in the above EP 1 449 543 A1 to treat the plugs after sealing the container and supplying hot water as washing liquid into the container within the same, thereby removing impurities such as particles or endotoxins from the surfaces of the plugs and transferring them into the washing liquid , The impurities are removed with the washing liquid from the container when it is completely withdrawn from the container after the washing process. After washing, the sealing plugs remaining in the container are sterilized by supplying saturated steam into the container before they are optionally dried after a preceding siliconization by supplying hot air.

However, the above-described washing, sterilization and drying of the sealing plugs can also be carried out in containers or plug cleaning systems of a different design, for example in systems with washing-drum-type containers.

In the drawing, the closed container 2 serving for washing stopper 6 is therefore only schematic shown. The container 2 has on its upper side a filling opening 4 for filling with sealing plug 6 and an opening into the container interior line 8, which is connectable via two controllable shut-off valves 10 and 12 optionally with a vacuum pump 14 or with a compressed air compressed air reservoir 16 containing compressed air. On the underside of the container 2 opens a supply line 18 for supplying washing liquid 20 into the container 2, which is connectable via a controllable shut-off valve 22 with a pump 24 and a container 26 for washing liquid. In place of the pump 24 and the container 26, a pressurized water ring is often present in pharmaceutical plants, from which the required water is removed.

Some types of plugs, such as the peristaltic plugs 6, enlarged one at a time and in cross-section, for an infusion bottle, have a recess 28 or cavity open on one side only, typically at the bottom of the plug 6. Such a recess 28 complicates a complete wetting of the plug 6 during the washing process, since an air bubble 30 can form during filling of the container 2 with the washing liquid 20 within the recess 28, even if the mouth of the recess 28 faces upward, as in the stopper 6 shown in the drawing.

In order to ensure complete wetting of the stopper surface despite blistering, the pressure p in the container 2 filled with the washing liquid 20 is alternately alternately lowered and increased during the washing process, as shown in the figures by a downwardly inclined arrow during the stopper 6 immersed in the washing liquid 20 and is covered by this.

In the embodiment shown in the figures, the container 2 is after introduction of the sealing plug 6 at atmospheric pressure into the vicinity of the filling opening 4 with the Washing liquid 20 filled so that it completely covers the plug 6. This condition is in Fig. 1 shown and shows that the plug 6 is not wetted by the washing liquid due to the air bubble 30 in the interior of the recess 28, so that there is no further purification of contaminants possible without further action.

In order to remove the air bubble 30 from the recess 28, a negative pressure is first applied in the container 2 by using the vacuum pump 14 via the above the liquid level of the washing liquid 20 into the container 2 opening line 8 air is sucked out of the container 2, such as represented by an arrow A. When the air is drawn off, the pressure within the washing liquid 20 decreases, as a result of which the volume of the air bubble 30 contained in the recess increases and part of the air bubble 30 leaves the recess, as in FIG Fig. 2 shown. As a result, the surface of the bladder 20 in contact with the washing liquid 20 increases, until finally the skin of the same breaks down in the region of the mouth of the recess 28 and from there outside washing liquid 20 penetrates into the collapsing air bladder 30, as in Fig. 3 shown. As a result, the part of the air bladder 30 located outside the recess 28 is detached and ascends as the bladder 32 in the washing liquid 20, as in FIG Fig. 4 shown. Upon reaching the liquid level, the air is then sucked by the vacuum pump 14.

When the air pressure measured above the washing liquid 20 is lowered from atmospheric pressure by 950 mbar to a pressure of about 50 mbar with the aid of the vacuum pump 14, it is repeated in the FIGS. 1 to 4 illustrated process several times, ie the increase in the volume of the air bubble 30 ( Fig. 2 ), the penetration of washing liquid 20 into the air bladder 30 (FIG. Fig. 3 ) and the detachment of a portion of the air bladder 30 ( Fig. 4 ). The prevailing in the washing liquid 20 hydrostatic pressure, which is unaffected by the lowering of the air pressure above the liquid level, has the consequence that the process takes place at plug 6 near the liquid level slightly more frequently than at plug 6 at the bottom of the container 2.

Due to the strong decrease in the pressure in the washing liquid 20, moreover, part of the air or air components dissolved in the washing liquid 20 leaves the washing liquid 20, which is important in the subsequent pressure increase.

When the air pressure above the liquid level of the washing liquid 20 reaches a predetermined value or does not decrease further in spite of continued operation of the vacuum pump 14, which is the case at a pressure of about 50 mbar, the vacuum pump 14 is closed by closing the shut-off valve 10 in the line 8 separated from the container 2 and turned off.

As indicated by an arrow B in Fig. 5 shown, the pressure in the container 2 is then increased abruptly by sterilized compressed air is fed into the container 2 by opening the valve 12 above the liquid level until the pressure in the container reaches about 2000 mbar. The rapid increase in pressure in the washing liquid 20 from 50 mbar to about 2000 mbar also causes a collapse of the air bubble 30 contained in the recess 28, wherein the skin of the bladder 30 breaks in the region of the mouth of the recess 28, so that washing liquid 20 into the bladder 30th flows. As in Fig. 6 illustrated, the air bubble 30 divides into several smaller air bubbles 34, 36, 38, 40, 42, 44, 46, of which those 40, 42, 44, 46, which do not adhere to the surface of the plug 6, to Surface of the washing liquid 20 ascend. In the case of the air bubbles 34, 36, 38 remaining in the recess 28, as a result of the increase in pressure, the bubble volume decreases approximately by a factor of twenty, as in FIG Fig. 7 represented, whereby only a very small surface in the recess 28 remains unwetted by the washing liquid 20. In addition, due to the increase in pressure, a portion of the contained in the bubbles 34, 36, 38 dissolves Air in the previously degassed washing liquid 20, with very small bubbles completely dissolve.

By repeating the cycle described above one to five times as needed, ie lowering the pressure in the container 2 and then abruptly increasing it again, the remaining bladders 34, 36, 38 can be completely removed from the recess 28 and their entire surface with the washing liquid 20 are wetted, as in Fig. 8 shown.

In order to facilitate the escape of last air residues also from the recesses 28 of plugs 6, in which the mouth facing down, the container 2 can be rotated in each case between two successive cycles to change the orientation of the plug 6 in the container 2.

To eliminate the last bubbles also contributes that is used as the washing liquid 20 heated water, which evaporates at the phase boundary to the air bubbles, when the pressure in the container 2 is lowered to below the boiling point of the washing liquid 20. This leads to an entry of steam into the bubbles, whereby their volume increases and thus the detachment from the surface of the plug 6 is favored. As a result, further air is discharged from the recess 28, so that in the subsequent pressure increases, the bubble volume continues to decrease, while the size of the surface wetted by the washing liquid 20 increases further.

Furthermore, it is also advantageous if, with the aid of the vacuum pump 14, a vacuum is applied to the container 2 filled with the stopper 6 even before the supply of the washing liquid 20 and maintained during the supply of the washing liquid 20 into the container 2. In this way, the amount of air trapped in the recesses 28 of the plugs 6 can be significantly reduced already during the filling of the container 2 with washing liquid 20.

Furthermore, a complete wetting of the stopper surface with the washing liquid 20 can also be accelerated by subjecting the container 2 first to a vacuum and then to steam, preferably saturated steam, after it has been filled with the stopper 6 and before the washing liquid 20 is supplied. The supplied into the container 2 steam is reflected in its relaxation in the form of smallest water droplets on the surface of the stopper 6 down. These water droplets wet the stopper surface, whereby, in particular, the endotoxins which are readily soluble in water dissolve in the water droplets and, upon melting of the droplets, pass into the aqueous washing liquid 20 which is subsequently introduced into the container.

By experiments on endotoxins contaminated specifically, i. spiked plug 6, it has been found that after a washing operation with a washing liquid consisting of pure heated water without detergents and a repeated pressure reduction and pressure increase of the flooded container, as described above, the endotoxins could be cleaned from the plugs 6 to such an extent that the permissible limits were far undercut.

Claims (15)

Method for washing smaller objects, in particular sealing plugs for pharmaceutical purposes, in which the objects are brought into contact with a washing liquid in a closed container in order to remove impurities from the surface of the objects, characterized in that the pressure in the container ( 2) is alternately lowered and raised with the objects (6) covered by the washing liquid (20). A method according to claim 1, characterized in that the pressure above a liquid level of the washing liquid (20) is lowered to a value of less than 100 mbar. Method according to one of the preceding claims, characterized in that the pressure in the container (20) is lowered below the boiling point of the washing liquid (20). Method according to one of the preceding claims, characterized in that the pressure in the container (2) is lowered by above a liquid level of the washing liquid (20) air is sucked out of the container (2). Method according to one of the preceding claims, characterized in that the pressure in the container (2) is alternately lowered and increased several times. Method according to one of the preceding claims, characterized in that the pressure in the container (2) is increased when in the container (2) a predetermined negative pressure has been reached or when no further decrease in the pressure in the container (2) is recorded more. Method according to one of the preceding claims, characterized in that the pressure in the container (2) is increased abruptly. A method according to claim 7, characterized in that the pressure is suddenly increased at least to atmospheric pressure. Method according to one of the preceding claims, characterized in that the pressure is increased to a value of more than 1500 mbar. Method according to one of the preceding claims, characterized in that for increasing the pressure of compressed air in the container (2) is supplied. Method according to one of the preceding claims, characterized in that the washing liquid is water which contains no detergents or surfactants. Method according to one of the preceding claims, characterized in that before the supply of washing liquid into the container (2) steam is passed into the container (2). A method according to claim 12, characterized in that before the introduction of the steam, a negative pressure on the container (2) is applied. Method according to one of the preceding claims, characterized in that the container (2) is moved during the pressure reduction and pressure increase. Method according to one of the preceding claims, characterized in that before and / or during the supply of washing liquid (20) in the container (2), a negative pressure on the container (2) is applied.

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