METHOD AND DEVICE FOR PASSIVATING THE INNER SURFACE OF A GLASS FLASK, AND FLASK OBTAINED WITH SUCH A METHOD

Abstract

The present invention relates to a method, a device for implementing the method, and a flask obtained by said method for passivating the inner wall of a glass container capable of containing a pharmaceutical grade material. To treat or inhibit the inner surface of the container, said inner surface of the container is treated via ion exchange between the container and an aqueous extraction liquid such that the measured hydrolytic resistance of said surface is divided by at least two.

Claims

1. A process for passivation of the inner wall of a glass container suitable for containing a product of pharmaceutical quality, wherein in order to passivate and/or inhibit the inner surface of the container, the process includes treating said inner surface of the container by ion exchange between the container and an aqueous extraction liquid so that the measured hydrolytic resistance of said surface is at least halved.

2. The passivation process as claimed in claim 1 wherein the aqueous extraction liquid is water of R1 quality.

3. The passivation process as claimed in claim 1, wherein the inner surface of the container is treated by at least three passes of the bottle in an autoclave at a temperature above 120 C. for a time greater than one hour, the aqueous extraction liquid being changed each time.

4. The passivation process as claimed in claim 1, wherein the extraction liquid is an acid aqueous solution with a pH corrected to 8.

5. The passivation process as claimed in claim 1, wherein, the container being a bottle, in order to carry out the ionic treatment the following steps are carried out at least once: bringing the inner face of the bottle into contact by filling, vaporization or flowing of the aqueous extraction liquid in the bottle, raising the temperature of the bottle with the extraction liquid inside the bottle and/or while maintaining a saturated atmosphere inside the container up to a given temperature greater than or equal to 80 C. and for a first given time set to avoid thermal shocks and to respect the internal stresses of said bottle, maintaining the bottle at this temperature for a second given time greater than or equal to 30 minutes, the inside of the bottle being kept entirely in contact with said liquid and/or said saturated atmosphere, cooling the bottle and the extraction liquid inside for a third given time set to avoid thermal shocks and to respect the internal stresses in the bottle, and emptying the extraction liquid if it has not been evaporated in a preceding step.

6. The passivation process as claimed in claim 5, wherein, the extraction liquid being acid, in order to bring the extraction product into contact with the inner wall of the bottle, the liquid is sprayed as a mist inside the bottle, at a temperature greater than 80 C. for the second given time which is greater than 30 min.

7. The process for passivation of the inner wall of a glass container as claimed claim 1, wherein the extraction liquid is introduced into the container in the form of ice.

8. The passivation process as claimed in claim 5, wherein the rise in temperature is carried out by a saturated-atmosphere electric annealing lehr.

9. A device for passivation of the inner surface of glass bottles, comprising: means for filling and/or vaporization of an aqueous extraction liquid in the bottles and an annealing lehr, means for keeping the atmosphere of the lehr saturated with said extraction liquid, means for transporting said bottles through said lehr for a given time, means for coding said bottles, and means for emptying said bottles if necessary after treatment.

10. A glass container having a free inner surface not treated with, and free of, sulfur and/or fluorine, the hydrolytic resistance RH of which is less than 50% of the lower limit indicated by the European Pharmacopeia for this type of bottle and glass and the alkali or alkaline-earth metal surface composition of which, over a thickness e10 m, is at least 5% lower than the composition of the glass in the bulk.

Description

[0077] The invention will better understood on reading the following description of embodiments described below by way of nonlimiting examples and with reference to the accompanying figures in which:

[0078] FIG. 1 is a flowchart showing the steps of a passivation process according to one embodiment of the invention.

[0079] FIG. 2 shows a flowchart of the steps of the process according to another embodiment of the invention.

[0080] FIG. 3 shows a curve of the change in the hydrolytic resistance RH as a function of the treatment conditions.

[0081] FIG. 4 schematically shows, in perspective, an embodiment of a device implementing the process described with reference to FIG. 1.

[0082] FIG. 5 shows, as a partial exploded view, an example of an inner wall of a container according to one embodiment of the invention, as obtained by the process described with reference to FIG. 1.

[0083] FIG. 1 shows the steps of the passivation process according to the embodiment of the invention more particularly described here, for the passivation of the inner face of one or more bottles, for example open pharmaceutical bottles, placed on rack-type removable supports.

[0084] After a first step 1 of supplying the bottles, these bottles are filled with aqueous extraction liquid (step 2), for example with water of R1 quality.

[0085] In an alternative embodiment, the aqueous liquid is sprayed as a mist inside the bottles, in a manner known per se, for example by means of individual nozzles automatically positioned opposite the opening of the bottles.

[0086] Spraying is suitable for ensuring a continuous thin film of liquid on a given surface of said bottles, which are then placed in a heated chamber (step 3), which is enclosed and maintained at a given hygrometry of extraction liquid.

[0087] The degree of hygrometry is for example 100%. In this way, the contact between the extraction liquid and the inner wall of the bottle is ensured continuously.

[0088] The heated chamber is for example an electric and/or gas-fired lehr or furnace. The bottles are then raised to a given temperature of between 70 C. and 150 C., for example 80 C., for a first time, for example of 15 min so as to avoid thermal shocks.

[0089] The temperature is controlled in a manner known per se and the bottle is then maintained (step 4) at said given temperature for a second given time, for example 40 minutes.

[0090] The bottles are then removed from the furnace (step 5) or from the heating zone thereof, in order to be cooled for a third given time, for example three minutes, here too with kinetics suitable for avoiding thermal shocks.

[0091] The final temperature obtained after cooling is for example ambient temperature.

[0092] The extraction liquid remaining is then emptied (step 6) if it has not been evaporated (test 7) in a preceding step.

[0093] In the embodiment described, steps 2 to 6 are repeated (test 8) for a given number of times, for example twice, so as to obtain a hydrolytic resistance lower than the previously chosen given threshold.

[0094] When several repetitions of the process are carried out, the aqueous extraction liquid is changed each time (repetition of step 2).

[0095] The bottles are then, but not compulsorily, rinsed then dried (step 9) before being stored for later use.

[0096] FIG. 2 gives the steps of the process according to the embodiment of the invention using an autoclave.

[0097] This autoclave is of the type known per se.

[0098] After a first step of supplying the bottles, these bottles are filled with aqueous extraction liquid and are closed, for example with a non-leaktight aluminum foil (step 2).

[0099] Next they are placed in an autoclave (step 3).

[0100] The contents of the autoclave are then brought, while respecting the temperature rise holds for avoiding thermal shocks, to the second given temperature (for example 121 C.) and to the corresponding pressure. It is maintained at these values for the second given time, for example greater than 1 hour (step 4).

[0101] The pressure inside the autoclave is suitable for keeping the extraction liquid in the liquid phase. For example for 121 C., the pressure is increased by 1 atm (atmosphere) relative to the ambient atmospheric pressure.

[0102] The temperature of the bottles is then lowered, for example to 80 C., while respecting the stresses of the glass (step 5).

[0103] The bottle is then emptied of its contents (step 6) and steps 2 to 6 are repeated (line 7) a number of times greater than three, for example five times or ten times (test 8).

[0104] The bottles are then drained after an optional rinsing (step 9).

[0105] Represented in FIG. 3 is the influence of the parameters P of the process on its efficiency.

[0106] The parameters P are the various given temperatures and times of the process, the pressure conditions used and the composition of the extraction liquid.

[0107] The curve C represents the change in the hydrolytic resistance (RH) of the inner walls of the bottles as a function of these parameters.

[0108] The greater the values of one or more of the parameters, the more aggressive the treatment and the faster the treatment kinetics.

[0109] Knowing that for a given glass and standard usage conditions PO (namely ambient atmospheric pressure and temperature), for water of domestic quality, the glass has a hydrolytic resistance Rh0 referred to as the reference hydrolytic resistance.

[0110] After treatment, as a function of the increase in the value of the parameters P, the hydrolytic resistance obtained for the treated glass Rh follows the curve C to a minimum Rmin (for parameters Ptmin).

[0111] The minimum resistance Rh then corresponds to a minimum subsequent release of elements from the glass into the contents.

[0112] It is less than Rh0/2.

[0113] But it is observed that an increase in the value of one of the parameters, relative to the minimum point Ptmin of the aggressiveness, on the other hand makes the hydrolytic resistance rise until it again passes through Rh0 for parameters PLim.

[0114] It is also observed that if the aggressiveness of the parameters is increased again beyond the limit PLim, the hydrolytic resistance is then deteriorated (due to the deterioration of the glass itself).

[0115] The invention proposes a process that makes it possible to remain within the (inverted) peak of the curve C (hatching in the figure).

[0116] An embodiment of a device D implementing the process from FIG. 1 will now be described with reference to FIG. 4.

[0117] The device D first of all comprises means 11 for transporting the bottles 12, such as for example a conveyor belt.

[0118] The bottles 12 are for example placed individually on the conveyor belt 11, or inserted into supports (not represented).

[0119] Means 13 for filling and/or vaporization/spraying of the aqueous extraction liquid 14 in the bottles are provided.

[0120] These means are known per se.

[0121] They are for example formed by injection nozzles 15, which fill or spray a given amount of liquid 14 in each of the bottles, for example by filling them to at least 80% of their volume.

[0122] The aqueous extraction liquid is for example water of R1 quality or citric acid-water with a pH corrected to 8.

[0123] In another embodiment, the extraction liquid is introduced into the bottles in the form of crushed ice which, for a given boiling temperature, lengthens the contact time between the liquid and the inner wall and protects from thermal shocks.

[0124] The device D comprises, positioned downstream of the filling zone on the conveyor belt, a furnace 16.

[0125] The furnace 16 is for example a heated saturated-atmosphere electric annealing lehr 17 that is known per se, that has heated curtains and that is in the form of a tunnel through which the bottles are therefore slowly made to pass.

[0126] The hot zone successively comprises, in the direction of the operation of the conveyor belt, a first subzone 18 for raising the temperature, a second subzone 19 for maintaining a given temperature and a third subzone 20 for cooling down to ambient temperature.

[0127] The conveyor belt 11 thus introduces the bottles 12 into the first subzone 18 of the annealing lehr 17 which gradually raises the temperature to a first given temperature, for example of 80 C.

[0128] The conveyor belt 11 then introduces the bottles 12 into the second heating subzone 19 that also comprises means 13 for keeping the atmosphere of the lehr saturated with the extraction liquid.

[0129] These means 13 comprise means for controlling the chamber of the furnace 17 and for supplying it with extraction liquid.

[0130] In some embodiments, the extraction liquid 14 is acetic acid introduced as a mist inside the chamber and therefore the bottles, at a temperature greater than 80 C. (for example 95 C.) for the second given time which is greater than 30 min.

[0131] But provision may also be made for injection nozzles (not represented) for injection of the acid mist, placed directly inside the hot zone (furnace or lehr).

[0132] The conveyor belt 11 has a suitable speed and/or a suitable length so that the bottles 12 remain in said lehr 17 for a given time, in particular at the desired operating temperatures.

[0133] The conveyor belt 11 makes the bottles 12 pass through the third hot subzone 20 comprising means for cooling said bottles.

[0134] These means (not represented) may be in the open air or under a controlled atmosphere. Here the control (start/stop), the speed and/or the length of the conveyor about 11 must allow a temperature rise/drop that is slow enough to prevent thermal shocks but suitable for the reaction kinetics.

[0135] The operation of the conveyor belt is therefore programmed and controlled accordingly.

[0136] In one embodiment, the bottles are emptied after treatment and closed for example with an aluminum foil 21 during the drop in temperature thereof, which will make it possible to keep their inner wall in an aseptic environment.

[0137] At the end of travel of the belt 11, the device also comprises, if necessary, means 22 that make it possible to tip over the bottles in a manner known per se, in order to empty them for example above a storage tank 23, before placing them in another work station.

[0138] The other work station may be a packaging unit.

[0139] It may also be a unit for rinsing the bottles when necessary, in particular if emptying was required.

[0140] On the other hand, if there is, along the path of the conveyor belt, a temperature zone greater than the boiling point of the extraction liquid, for a sufficient time, the bottle 12 will a priori have no need of a rinsing step.

[0141] It may finally be another treatment device D and/or gripping means that make it possible to place the bottles back at the start of the line in order to repeat the treatment a given number of times.

[0142] A bottle according to one embodiment of the invention will now be described with reference to FIG. 5.

[0143] The bottle 25 (represented as a partial, exploded, cross-sectional view) is formed of glass 26 constituted of a chemical network, of which forming ions provide the structure, and modifying ions, of weaker chemical bond with the network, and which form the elements (residual chemical species released) of which the invention proposes in particular to reduce the amount released.

[0144] For example, the forming ions are SiO.sub.2, Al.sub.2O.sub.3 present at close to 74% of the total mass and B.sub.2O.sub.3 present at close to 12%.

[0145] The network-modifying ions are for example Na.sub.2O and/or K.sub.2O up to the remaining percentage.

[0146] While the surface is in contact with the liquid, a substitution reaction takes place in the glass between the hydrogenated ions of the liquid solution and the other ions of the glass.

[0147] Thus, the inner surface 27 of the container 25 carries out an ion exchange between the container and an aqueous extraction liquid 14 so that the hydrolytic resistance of said surface 27 is at least halved in absolute terms (resistance capacity multiplied by 2).

[0148] The ion exchange thus produces a passivation of the container.

[0149] The bottle from FIG. 5 was treated by a process according to the invention.

[0150] It has a free inner surface 27 which was depleted of releasable chemical elements over a very thin thickness e for example of less than 10 m.

[0151] If said bottles 25 are subsequently not treated, they are then free of sulfur and/or fluorine, and have a hydrolytic resistance R.sub.H of less than 50% of the lower limit indicated by the European Pharmacopeia for this type of bottle and glass.

[0152] Depending on the quality of the glass initially supplied, the bottles, after treatment by the invention, have a hydrolytic resistance of the inner wall at the very least of less than 20% of the lower limit indicated by the European Pharmacopeia.

[0153] Given in the table below are the results of measurements carried out, following the standardized ISO measurement protocol already mentioned with various treatments according to the invention:

TABLE-US-00001 TABLE Difference between the Treatment RH Average average and the Test conditions results RH reference 0 Reference 0.2 0.14 0.00 0.1 0.15 0.14 0.12 0.13 0.15 0.14 0.16 0.19 0.12 0.13 1 ice - capped bottle/ 0.1 0.09 0.05 introduction at 0.1 20 C., increase to 0.08 600 C. at 300 C./h (hold 30 min at 600 C.) 2 Acetic mist, 20 min 0.06 0.06 0.08 0.06 0.06 3 Acetic mist, 30 min 0.04 0.06 0.08 0.12 0.01 4 3% citric acid, pH = 0.11 0.11 0.03 8, oven 80 C. 24 h, 0.12 Al-capped bottle 0.1 5 3% citric acid, pH = 0.12 0.11 0.03 8, oven 90 C. 24 h, 0.14 Al-capped bottle 0.07 0.42 0.52 6 0.1N NaOH, 24 h 00 excess 0.11 0.03 at ambient 0.11 temperature (capped 0.1 bottle) 7 Autoclave, R1 water - 0.1 0.05 0.10 121 C. three cycles 0.03 0.07 0.07 0.08 0.03 0.03 0.02 0.04 0.03 0.05 0.03 0.02

[0154] Each implementation corresponds to specific parameter conditions specified in the Test conditions column.

[0155] For each RH results line, the value of a hydrolytic resistance measurement carried out (for example there were 13 measurements for test 7) is expressed.

[0156] For a same test, the measurements are averaged in the Average RH column. Each average is compared with the reference measurement from test 0 and the difference between the two appears in the Difference between the average and the reference column.

[0157] The reference conditions are those considered above to be the standard conditions giving a base hydrolytic resistance R0, with a bottle stored empty after cooling for several weeks (having from that moment undergone a natural aging under relatively long standard conditions of storing in open air).

[0158] After filling with water under the standardized conditions, the test mentioned above is then carried out with measurement of the pH.

[0159] In the tests carried out as described with reference the table, everything which is extracted from the glass is measured, including the silica which constitutes a good portion thereof, and more specifically all the alkali metals, alkaline-earth metals, and also the forming ions (and not only sodium).

[0160] In other words, it is a measurement that makes it possible to determine everything released independent of the amount of sodium.

[0161] A negative result of the difference indicates that the treatment carried out under the conditions indicated improved the hydrolytic resistance of the bottle considered.

[0162] Conversely, a positive result would indicate a degradation.

[0163] Thus, the measurements carried out reveal that the embodiment from test 7, in which the process is carried out by an autoclave with water of R1 quality at 121 C. for three one-hour cycles makes it possible to reduce the hydrolytic resistance by almost three times and therefore to make it almost three times better.

[0164] As goes without saying and as also results from the aforementioned, the present invention is not limited to the embodiments more particularly described. On the contrary it encompasses all the variants and especially those where the number of cycles, the temperatures, the pressures, and the durations are determined differently, as a function of the glass and of the desired results, those where the container is a pot or another glass container, and those where the hot subzones themselves comprise subzones for varying the temperature below and/or above said temperatures.