MXPA97008366A - Device and process for mixing a pharmaceutical composition with another agent and method for the oral administration of farmaceut preparation - Google Patents

Abstract

The present invention relates to a device for mixing a pharmaceutical composition stored in a chamber (38) in the device, with an agent that is to be added a little before the administration to form a preparation to be administered. The device should be able to shake without dripping. It comprises a hollow body (2) having an outlet (4), sealed by a removable closure (12) and plunger (6), which includes a flexible sealing member (20) having a circumferential edge in sealed or sealed contact with the wall inside (8) of the hollow body. The symbol (6), the hollow body (2) and the removable closure (12) define the chamber (38). A hollow rod (30) is connected to the piston (6) to displace it in the hollow body (2) and includes at least one opening or orifice, which communicates with the inside of the rod (30) with the upper side of the flexible member ( twenty). The flexible member (20) is supported on the plunger (6) in such a way that it can only flex downwards. At a certain predetermined differential pressure on the upper side and lower side of the flexible member (20), the flexible member will flex downward to open a communication in the inner wall (8) of the hollow body, towards the chamber (38), such so that the agent flows into the camera (3

Description

DEVICE AND PROCESS FOR MIXING A PHARMACEUTICAL COMPOSITION WITH ANOTHER AGENT AND METHOD FOR THE ORAL ADMINISTRATION OF THE PHARMACEUTICAL PREPARATION FIELD OF THE INVENTION The present invention relates to a device for mixing a pharmaceutical composition, preferably dry and granular, with another agent, preferably fluid, for a preparation, preferably a gel / in accordance with the preamble of claim 1.

BACKGROUND OF THE INVENTION The main problem, which forms the basis of the present invention, relates to the handling, storage and administration of a pharmaceutical composition to be mixed with another agent, which may adversely affect the stability of the composition, to form a preparation convenient for administration to a living being, especially an animal.

REF .: 025873 It is well known, in the veterinary technique, to administer, to horses, pharmaceutical compositions in the form of paste-like preparations, by means of a device similar to a syringe. The syringe is then inserinto the horse's mouth and the preparation is expelled on the root or base of the tongue. The viscous nature of the preparation and the placement of it in the back of the mouth, makes it difficult for the horse to spit out the preparation. In some cases these preparations, for example those comprising a mixture of a pharmaceutical composition and a consistency forming agent, will have a short storage stability. Therefore, the components comprised in these preparations must be kept isolafrom each other until a little before their use, when they are mixed with each other to form the desired preparation. There are a plurality of solutions to the problem of storing and mixing two components in a preparation, which can not be stored for a long period of time after they have been mixed.

The previous, more common solution is a syringe of the type described in US-A-3, 3 0, 873, which has a plunger, accommodaso that it can slide, in a cylindrical body. The two components that are to be mixed are contained in two different compartments, isolafrom one another by means of a diaphragm. A little before the preparation is going to be used, the diaphragm is broken or punctured in such a way that communication is established between the two compartments. The syringe with the mixture is then stirred to form a homogeneous preparation. After this operation a lid is removed to open a duct and the contents are expelled through a needle, pressing the plunger. This type of prior art has proven, in most cases, to be satisfactory and reliable, and it is also relatively easy to manufacture, for example by injection molding, plastics, at low cost. However, the above syringe is not suitable for the administration of a gel, mainly due to the presence of a needle. But apart from this, generally, the mixing devices, which have two compartments isolafrom each other by a thin rubber or plastic diaphragm, could not be used for certain types of moisture-sensitive pharmaceutical compositions. An example of one such composition is that composition containing a proton pump inhibitor, such as omeprazole, which degrades during long-term storage in the presence of moisture. Molecular migration, always present, through a rubber or plastic diaphragm, would be sufficient to cause degradation of these sensitive compositions during long-term storage. Thus, conventional two compartment devices are not suitable for those compositions. Danish Patent Specification 112,893 filed July 25, 1966 describes a syringe for injection, for injection of a pharmaceutical composition that can not be stored in solution for a longer period of time, without harmful effects. The syringe basically corresponds to a standard syringe and the difference is that the hole in the needle fitting is sealed by a diaphragm. The composition is contained in the syringe, in dry form. When the syringe is to be used, an injection needle, double-ended, is mounted on the needle attachment, and one of the tips of the needle breaks the diaphragm. Solvent is aspirated into the syringe through the needle. The syringe is then agitated and the resulting solution is injected through the needle. A disadvantage of this type of syringe is that the filling operation is quite complex, and requires the assembly of a double-ended injection needle to break the diaphragm. In addition, after rupture of the diaphragm, the mixing chamber will be open to the air, so care must be taken during the stirring operation to prevent the mixture from dripping out through the needle. In addition, due to the high flow resistance of the syringe, due to the narrow passages in it, in particular in the needle, it could not be used for viscous, pasty or gel-like preparations. In addition, this known apparatus is not convenient for administration due to the existence of the needle. In addition, the manufacturing costs for the syringe will be relatively high.

OBJECTIVE OF THE INVENTION An object of the invention is to avoid the disadvantages of the prior art, by providing a mixing device, in which a pharmaceutical composition can be stored for a longer period of time and in which a desired agent can be added, easily and quickly, immediately before the administration of the preparation. After the addition of the agent, the device will also be able to be vigorously stirred without leakage. In addition, the manufacturing cost for the device of the invention should be relatively low. This object of the invention is achieved by a device in accordance with the preamble of claim 1, which includes the features of the characterizing part of claim 1. The additional, independent claims define processes that use the device to mix a pharmaceutical preparation and methods for the administration of a mixed preparation, by the device. When it is going to be used for the administration of the preparation, it is necessary to first remove a package or seal that protects the pre-filled chamber, against moisture, during storage. Then, the agent to be mixed with the composition contained in the chamber is supplied while the fluid agent is separated from the chamber by the flexible sealing or sealing member. Then the plunger moves in the opposite direction, towards the direction of expulsion, causing an expansion of the closed chamber, defined by the plunger, the side wall portion and the lid, whereby a vacuum is created in the chamber. Initially the differential pressure on the sealing member will be too low to flex it, but when the piston continues to be displaced, the vacuum in the chamber gradually increases such that the sealing member deforms and loses contact with the wall, thereby establishes communication towards the camera. The agent will then be sucked into the camera. When the required amount of the agent has been drawn into the chamber, and the flexible sealing member has been flexed back to its resting position, the device is shaken until the preparation is ready for administration. Just before the administration is to be carried out, the closure is removed to the chamber and the device is inserted, for example, into the mouth of a horse. The contents of the device are now ejected by pressing the plunger.

DESCRIPTION OF THE PREFERRED MODALITIES Preferred embodiments of the invention will now be described, by way of example, with reference to the drawings, in which: Figure 1 is an axial section of a first embodiment of the invention, Figure 2 shows the portion, enclosed in a circle, of Figure 1, on a larger scale, Figure 3 is a cross section, along line III-III of Figure 1, Figure 4 is an axial section of an additional embodiment, which is slightly modified with respect to that of Figures 1-3, Figure 5 shows the portion, enclosed in the circle, of Figure 4, on a larger scale, Figure 6 is a section along line VI-VI of Figure 4, Figure 7 shows a part of a slight modification of the modality of Figure 4, on a larger scale, Figure 8 is an axial section of yet another embodiment of the invention, Figure 9 is a section along line IX-IX of Figure 8, Figure 10 shows the portion, enclosed in the circle, of Figure 8, on a larger scale, and Figure 11 describes a slight modification of the modality of Figures 8-10.

As shown in Figure 1, the syringe-like device, of the first preferred embodiment of the invention, comprises a hollow, elongated, tubular, cylindrical body 2, which is open at both ends. The lower end of Figure 1 is the output end 4. A plunger 6 is inserted through the open upper end 10. A flange portion or a portion 13 for gripping with the fingers extends substantially perpendicular to the direction longitudinal of the hollow body 2 around the upper end thereof. The exit end 4 is closed by a removable cover 12, having a groove 14 having a diameter corresponding to that of the side wall 8 of the hollow body 2. The groove 14 is constructed with a depth that provides a hermetic seal with the lower end 4 of the cylindrical body, inside the body hollow 2. The lid 12 has a radially extending ear or projection 16 to facilitate removal of the lid 12 when the preparation is to be expelled. As can be seen in the best form, in Figure 2, the plunger 6 is comprised of two parts 18, 20, a support means 18 in the form of a diametrically extending flat cloth or membrane, perpendicular to the axis of the hollow body 2 and a sealing member 20 in the form of a thin flexible disk, which when discharged, is sized to make contact, in a sealed manner, with the inner wall 8 of the hollow body 2, whereby it isolates the spaces on each side. side of shutter member 20, of the other spaces. The disc 20 is provided in the center with a protrusion or nipple 22 having a convoluted, compressible end portion 24, while the fabric 18 has a central opening 26 having a smaller diameter than the warped portion 24. The stem or The rod 28 of the projection 22 is adapted to the thickness of the fabric 18 in such a way that the projection 22 can be introduced under pressure into the opening 26, so that the disc 20 will be close to the fabric 18. A rod 30 is made, in one piece, with the plunger 6. Its external diameter is somewhat smaller than the internal diameter of the hollow body 2, such that the rod 30 is guided by sliding inside it. The rod 30 is tubular, and its annular end portion 32 is made in one piece with the fabric 18. The end face of that portion 32 is flush with the end face (the lower face in Figure 1) of the fabric 18. At the open end 40 of the rod 30 a radially extending finger grip 23 is provided. The flexible disc 20 is made of a resilient material and will deflect when subjected to a sufficiently large force and will return to its original position upon withdrawal of force. When the cap 12 or other seal is placed on the exit end 4, a closed chamber 38 is defined, by the lid 12 or another seal, the flexible disc 20 and the inner wall 8 of the hollow body, and the volume of that chamber it is variable due to the plunger 6 which can be displaced axially. When pressed into the hole 26, the unloaded disk 20 rests against the fabric 18 and the annular end portion of the rod 30. Thus, the circumferential edge portion 34 of the disk 20 is prevented from being bent towards up by the fabric 18 and the annular end portion 32. On the other hand, the edge portion 34 is allowed to flex downwards. If this occurs, the edge portion 34 will lose its sealing or sealing contact with the inner wall 8 of the hollow body 2, whereby a communication is opened in the wall 8 between the upper and lower sides of the flexible disk 20. The disk 20 functions as well as a check valve. It should be noted that any method can be used to attach the resilient disk 20 to the rod 30. For example, a keyhole connection could be used. A keyway opening is then provided at the bottom end of the rod 30 and the projection or nipple 22 of the plug disk 20 is then inserted through the wider opening of the keyhole and then pushed into the narrow slot. slit of the keyhole. In yet another method of attachment, the flexible disk 20 may be provided with a portion of the rod in the center thereof, and that portion is then introduced into an opening provided in the lower end of the rod 30. The end of the stem or rod it is then heated to a softening temperature and then flattened to form a connection similar to a rivet joint. As mentioned above and as can be seen in Figures 1-3, the rod 30 is tubular and has an open bottom which is normally sealed by the flexible disc 20. The interior 36 of the rod 30 and the disc 20 form a filling compartment, for the agent to be mixed with a composition contained in the camera. The function of this first embodiment of the device will now be described in the manner of an example. A composition suitable for the device is described in WO / SE94 / 25070. In the following example the pharmaceutical composition is constituted by beads or granules of an active substance, such as pellets of omeprazole, multilayer, enteric coated, mixed with a gel-forming agent, such as xanthan gum, guar gum , carob gum, tragacanth, modified cellulose derivatives or the like, and to this mixture of dry components a fluid agent such as for example water is then added, to form a viscous gel. The use of the device defined by the present invention will not be restricted to use in relation to a preparation of omeprazole. A suitable dosage, of a dry mixture, of omeprazole pellets, of several layers, with enteric coating, is introduced into the chamber 38. A buffering agent or an agent for pH adjustment, such as citric acid, can be added to Prevent premature dissolution of the coated, enteric beads when water is added to the composition. This operation could be carried out in two ways, one is that the plunger 6 is placed in a suitable position, in the hollow body 2, with the lid 12 removed, and then the filling takes place, through the lower end 4, u another is that the lid 12 is applied on the lower end 4, with the plunger 6 removed, and the filling takes place via the upper opening 10. The amount or volume of mixing is optional within certain limits, since the volume of the chamber 38 is variable due to the piston 6 that can be displaced axially. When the filling is completed, the lid 12 or another seal is applied to the end 4 or the plunger 6 is inserted in the hollow body 2, respectively. It should be noted that the hollow rod 30, in an advantageous manner, serves as a measuring or grading device, for the agent to be added to the chamber 38. It is transparent and is preferably provided with graduation lines in such a way that the agent to be added can be measured precisely with the device. The excess agent can be poured out of the rod 30 before the rod 30 has been moved to open a communication in the chamber 38. Thus, due to the built-in graduation means, provided by the particular design of the rod 20, a measurement can be made very precise of the agent that is going to be added, without needing any additional means than the syringe itself. In view of the hygroscopic nature of the gel-forming agent, and the required durability, of several years, for the pharmaceutical composition, the contents of the chamber must be protected against penetrating moisture that would otherwise accumulate in the forming agent. of gel to cause, sooner or later, the degradation of omeprazole during long-term storage. Therefore, after the filling operation, the device is enclosed in a moisture-tight envelope, preferably having a moisture barrier, made of aluminum, although other materials that serve the same purpose can also be conceived. Conveniently a desiccant material is enclosed, preferably in a sachet, inside the envelope, as a further protection against moisture. As an alternative to the above package, it could be sufficient to provide a waterproof seal or lid, of a similar material, on the open end 40 of the rod 30. A desiccant could then be incorporated into the seal or cap, to absorb any penetrating vapor. The device could now be stored for several years until it is used. When it is going to be used, the device is removed from the moisture-tight package, or the seal that is on top of the tubular rod 30 is removed. Then, an adequate amount of water to be added to the mixture inside the chamber 38 is filled in the tubular compartment of the rod 30 to a desired level (marked with a graduation line or level mark). The plunger 6 is then moved upwards, thus creating a vacuum in the chamber 38. After a sufficient displacement the vacuum will be quite strong therein such that the flexible disk 20 will flex downwards, the circumferential edge 34 of the disk flexible 20 will lose its sealing or sealing contact with the inner wall 8, in such a way that communication is established from the compartment 36 towards the chamber 38, so that the water that is in the compartment 36 of the rod 30 will be sucked towards the chamber 38. When the water has been transferred into the chamber, the disc 20 will flex back to its resting position and then the device is shaken until a viscous gel containing the omeprazole pellets has formed. During the stirring operation, the flexible disk 20 prevents the mixture from leaking into the compartment 36. The mixture could be stored in the device for a short period of time before administration. Just before administration the lid 12 is removed and the device is placed where the preparation is going to be administered. The preparation is then expelled by pressing the rod 30. Conveniently, the rod 30 has an axial length such that, when it is fully depressed, the entire preparation is ejected from the device. Preferably, the flexible disk 20 has a flat surface to eject the composition completely, thereby avoiding the risk of some debris, pellets or gel remaining in the openings or slits, which could happen with a split disc. Instead of the plastic cap 12 a breakable or peelable seal could be provided to seal the chamber 38. Figure 4 demonstrates a slight modification of the embodiment of Figures 1-3. Instead of being open at the bottom end, the tubular rod 30a has two longitudinally opposite slits 42 extending from the bottom portion of the rod 30a to about half the height of the rod 30a and the upper side of the disk 20a. The bottom portion comprises an opening 26a in the center, which functions in a similar manner to the opening 26 of the embodiment of Figure 1. The bottom portion of the rod 30 is circular and provides support for the middle portion of the flexible disc 20 a. In a further modification of the embodiment of Figure 4, the sealing member 20'a forms a single piece with the rod 30'a and consists of a flexible, annular ring, see Figure 7. The advantage of this mode is that it is only it requires a single operation in the manufacture of the rod 30 'and the sealing member 20' a. Even in a further embodiment (Figures 8-10) of the previously described embodiments, the upper part of the rod 30b is tubular, while the lower part 46 thereof has a section in the shape of a cross, as can be clearly seen in the FIG. Figure 9. Thus, the lower part consists of two perpendicular wall portions 48, 50, extending longitudinally, and extending from the bottom portion of the rod 30b to approximately half the height of the rod 30b. From the tubular portion 44 and extending downwardly of the cross-shaped portion 46, it includes a first part that has a constant section to provide sufficient stiffness and guidance against the inner wall 8. The next part 56 tapers down and toward the bottom portion, which in turn comprises an annular rim 60 for supporting the flexible disc 20b and preventing it from flexing upwards. The bottom portion also includes an opening 62 into which the camber or projection 24b of the flexible disk 20b is pressed (see Figure 10). In Figure 11 a modification of the modality of Figures 8-10 is shown. As in Figure 7 the shutter member 34'b, flexible, forms a single piece with the rod 30b, which has an annular rim 60 'which protrudes radially and which is extended by a flexible, thinner annular rim 34'b, making obturating contact with the inner wall 8 of the hollow body 2. In the embodiment of Figures 8-11 the water to be added is introduced as above, through the open end 40 of the rod 30b but in opposition to the modalities previously described, the water will not be contained in a tubular portion. bottom, of the rod, but will rise along the cross-shaped portion to the desired level. In this case the cross-shaped portion could be provided with colored lines to indicate the volume levels. In these modalities the rod must not be transparent but may be made in an appropriate color. As can be understood, all modalities work in a similar way. A fluid agent, preferably water, is filled by the upper end 40 of the rod 30, and this water then flows through the opening provided in the rod and subsequently reaches the upper side of the flexible sealing member. The sealing member prevents the water from reaching the chamber 38. The rod will move after returning thereby creating a certain vacuum in the chamber 38. The combined action of the water weight and the vacuum will flex the sealing member downwards, such that water will be sucked into the chamber 38. When the water has disappeared from above the flexible sealing member, inside the chamber, the member will flex back to its original resting position and seal the chamber 38. The described solutions offer different advantages If the shutter member is a separate construction detail, it offers great freedom in the selection of the material. The material of the sealing member can be chosen in such a way that it has an optimum seal and elastic properties, while the material of the rod can be selected in such a way as to provide sufficient stiffness and support for the sealing member. If the rod and the sealing member are made in one piece, the selection of the material should be a compromise between the stiffness required for the rod and the need for flexibility and elasticity of the sealing member. However, this latter solution offers advantages with respect to manufacturing costs. It should further be noted that in both embodiments all the elements may be made of polymeric materials such as for example polyethylene, polypropylene, polyester, elastomer, polycarbonate, rubber or silicone, and manufactured by cheap, conventional methods, such as injection molding. . In addition, all the details have a simple construction and are easy to assemble. Consequently, the devices can be produced at low cost. In the embodiments of the invention, described above, the lid 12 is provided with a radially protruding ear 16, which extends around a portion of the circumference of the lid 12 and forms a grip portion to facilitate the removal of that lid. element. It should be understood that the grasping portion can have any suitable configuration. For example, it could be oval, or it could be constituted by a protruding flange that extends over the entire circumference of the lid. The devices are in particular suitable for oral administration to an animal, especially a horse, in particular, an aqueous gel containing a formulation of a proton pump inhibitor, for example omeprazole, or a similar composition. However, it will be apparent to those skilled in the art that the use of the device is not restricted to this field, since it can be used to mix various types of pharmaceutical compositions with other agents, and for oral, rectal or any other administration. another type of adequate administration, to many different types of living beings, including humans. It should also be noted that a pharmaceutical composition, in the sense of this application, not only means a drug but also that this expression is intended to include other types of beneficial agents, for example essential nutrients. It is noted that in relation to this date, the best known method for carrying out the aforementioned invention is that which is clear from the present description of the invention. Having described the invention as above, the content of the following is claimed as property:

Claims (32)

1. A device for mixing a pharmaceutical composition, preferably a dry and granular composition, with an agent for preparation, preferably fluid, which is preferably a gel or the like, and subsequently administering that preparation to a living being, for example an animal or a human, the device comprises a hollow body having an outlet sealed by a removable closure a plunger that is accommodated so that it can be displaced in the hollow body and in sealed or sealed contact, with an inner wall of the hollow body, a means actuator that is connected to the plunger to displace it in the hollow body, characterized in that the hollow body and the removable closure define a chamber for the composition, the plunger comprises a sealing member having a flexible edge portion in sealed or sealed contact , with the inner wall of the hollow body, one side of the edge portion facing the chamber, separating or so the chamber on the opposite side of the flexible edge portion, the edge portion is supported to be able to flex in a sufficient degree, in one direction only to lose its sealing contact with the inner wall of the hollow body to establish a communication between the chamber and the opposite side of the edge portion when the plunger moves in a direction away from the chamber.

2. A device according to claim 1, characterized in that the driving means is a tubular rod provided with at least one opening or hole in the bottom portion thereof.

3. The device according to claim 2, characterized in that the rod has a fabric or membrane extending diametrically between the edges of the fabric and the inner wall of the tubular rod.

4. The device according to claim 3, characterized in that the fabric has an opening in the center, adapted to connect, so that it can be disconnected, the sealing member, flexible, to the rod and the sealing member is circular and extends at least towards the inner wall of the tubular rod.

5. The device according to claim 2, characterized in that the circular rod has a bottom, closed portion, and axial slits extending from the bottom portion.

6. A device according to claim 5, characterized in that the flexible sealing member is a circular disk, fixed, so that it can be disengaged, to the bottom portion.

7. The device according to claim 6, characterized in that the flexible sealing member forms a single piece with the tubular rod and consists of a flexible annular ring that extends radially from the bottom portion to the inner wall of the hollow body.

8. The device according to any of claims 2 to 7, characterized in that the tubular rod includes a means for measuring volume, to add the agent.

9. The device according to claim 8, characterized in that the tubular rod has level graduations to add the agent.

10. The device according to claim 8 or 9, characterized in that the tubular rod is transparent.

11. The device according to claim 2, characterized in that the rod includes a first tubular part connected to a second part that has the shape of a cross.

12. A device according to claim 11, characterized in that the second part tapers toward the bottom portion of the rod.

13. The device according to claim 11 or 12, characterized in that the rod has a bottom portion formed by a plate, having a central opening adapted to connect, so that it can be disengaged, the flexible sealing member to the rod, and the The shutter member is circular and extends towards the inner wall of the hollow body.

14. The device according to claim 11 or 12, characterized in that the flexible sealing member forms a single piece with the rod and consists of a flexible annular ring extending radially from the bottom portion to the inner wall of the hollow body.

15. The device according to any of claims 11 to 14, characterized in that the second cross-shaped part includes a means for measuring the volume to add the agent.

16. The device according to claim 15, characterized in that the second part has level graduation, to add the agent.

17. The device according to claim 16, characterized in that the level graduations are colored lines.

18. A device according to any of claims 11 to 17, characterized in that the second part is colored.

19. The device according to any of claims 2 to 18, characterized in that the tubular rod includes an open end away from the plunger, which is closed by a moisture-proof seal.

20. The device according to any of claims 1 to 19, characterized in that the closure is a removable lid.

21. The device according to any of claims 1 to 19, characterized in that the removable closure is a closure that can be broken or that can be detached by tearing.

22. The device according to the preceding claims, characterized in that the chamber is prefilled with the pharmaceutical composition and the device is enclosed in a moisture proof envelope, which comprises at least one moisture barrier.

23. The device according to claim 22, characterized in that the at least one barrier against moisture is comprised of an aluminum layer.

24. The device according to claim 22 or 23, characterized in that the desiccant is contained in an envelope.

25. The device according to any of the preceding claims, characterized in that the pharmaceutical composition is constituted by pellets or coated beads, multilayer, enteric, comprising a proton pump inhibitor, for example omeprazole beads, mixed with an agent gel former, dry.

26. The process for preparing a pharmaceutical preparation, by mixing a pharmaceutical composition, preferably dry and granular, with an agent, preferably fluid, a little before the administration thereof to a living being, characterized in that it comprises the following steps: a) filling the composition in a chamber 38 of a device comprising a hollow body and a displaceable piston thereon, in sealed or sealed engagement with an inner wall portion of the hollow body; whereby an end wall, mobile, of that chamber is defined, the plunger comprises a sealing member having a flexible edge portion in contact sealed or sealed with the inner wall of the hollow body, separating the chamber from the opposite side of the portion of edge, the edge portion is capable of flexing to allow communication between the chamber and the opposite side of the edge portion, b) closing the chamber with a closure c) providing a moisture-tight seal, for the filled chamber , d) store the device until the time it is going to be used, e) remove the humidity-tight seal from the chamber, f) expand the chamber by moving the plunger whereby a communication is established between the cause of the opening of the edge portion, whereby fluid agent is transferred to the chamber g) if required, shake the device until the preparation is formed, h) provide an opening or hole in the chamber by removing the closure when the preparation is to be administered, allowing the preparation to be expelled from the device by moving the plunger towards the opening.

27. The process according to claim 26, characterized in that the moisture-tight seal, in step c) to the chamber is made by enclosing the device in a moisture-tight envelope which comprises at least one moisture barrier.

28. The process according to claim 27, characterized in that the at least one moisture-proof barrier is an aluminum layer.

29. The process according to any of claims 26 to 28, characterized in that the pharmaceutical composition is constituted by pellets or coated beads, enteric, a proton pump inhibitor, for example pellets of omeprazole, mixed with an agent dry for gel formation, and the preferred fluid agent is water.

30. The method for the oral administration to a living being, of a pharmaceutical preparation, characterized in that it is achieved by mixing a preferably dry and granular composition, with a preferably fluid agent, by the use of a device according to any one of the claims 1. at 25

31. The method according to claim 30, characterized in that the living being is an animal, for example a horse.

32. The method according to claim 31, characterized in that the device is inserted in the mouth of the horse just in front of the first premolar tooth, and the preparation is deposited on the root or base of the tongue. SUMMARY OF THE INVENTION The present invention relates to a device for mixing a pharmaceutical composition stored in a chamber (38) in the device, with an agent that is to be added a little before the administration, to form a preparation to be administered. The device should be able to shake without dripping. It comprises a hollow body (2) having an outlet (4), sealed by a removable closure (12) and a plunger (6), which includes a flexible sealing member (20) having a circumferential edge in sealed or sealed contact with the inner wall (8) of the hollow body. The plunger (6), the hollow body (2) and the removable closure (12) define the chamber (38). A hollow rod (30) is connected to the plunger (6) to displace the same in the hollow body (2) and includes at least one opening or orifice, which communicates with the interior of the rod (30) with the upper side of the member flexible (20). The flexible member (20) is supported on the plunger (6) in such a way that it can only flex downwards. At a certain predetermined differential pressure on the upper side and the lower side of the flexible member (20), the flexible member will flex down to open a communication in the inner wall (8) of the hollow body, towards the chamber (38), of such that the agent flows into the chamber (38).