Fluid product dispensing device

Abstract

Fluid product dispensing device comprising a metering valve mounted on a reservoir (1) containing at least one active ingredient suspended in a pressurized propellant gas whose liquid density at 21°C is less than or equal to 1.20 g / cm3, said valve comprising a valve body (10) containing a metering chamber (20), and a valve (30) sliding axially in said valve body (10) between a rest position and a dispensing position, to dispense the contents of said metering chamber (20), said metering chamber (20) being, in the rest position of the valve (30), connected to said reservoir (1), to allow the filling of the metering chamber (20) by gravity when, in the rest position of the valve (30), the valve is in an inverted position with the metering chamber (20) arranged below the reservoir, and to allow the emptying of said metering chamber (20) by gravity when, in the rest position of the valve (30),the valve is in an upright position with the metering chamber (20) arranged above the reservoir, said valve body (10) comprising at least one fluid passage opening (11), defining a passage surface S1 connecting said reservoir (1) to the interior of said valve body (10), said passage surface S1 being greater than or equal to 20 mm² and less than or equal to 100 mm². "figure for the abstract: figure 1",

Description

Title of the invention: Device for dispensing fluid product

[0001] The present invention relates to a fluid product dispensing device comprising a metering valve of the non-priming type.

[0002] So-called metering valves, in which each time the valve is actuated, a precise dose of fluid product is dispensed, are well known in the state of the art, and are generally assembled on a reservoir containing the fluid product and a propellant gas used to expel the dose.

[0003] Two types of metering valves are known in particular, namely on the one hand so-called retention valves which, after filling the metering chamber, seal it in a sealed manner until the next actuation of the valve, and on the other hand those which only fill just before the actual actuation, and which are called valves without priming or Primeless valves.

[0004] For retention valves, there may be a problem of incomplete dose and / or non-homogeneity of the dose at the time of its expulsion, in particular if the valve has been stored for a certain time, which means that the active ingredient is no longer distributed perfectly homogeneously in the dosing chamber. In addition, these retention valves may cause priming problems, which may require the user to operate the valve twice to be sure of obtaining a complete dose.

[0005] To avoid these problems, non-priming valves allow the metering chamber to fill quickly when the user is about to actuate the valve. With this type of non-priming valve, after each actuation, the metering chamber can refill, but if the valve is then stored in an upright position, then this metering chamber can empty into the reservoir, the metering chamber then not being sealed.

[0006] Furthermore, about fifteen years ago, for ecological reasons, the propellants previously used, which were generally CFC-based, were replaced by other propellant gases, namely HFA-134a and / or HFA-227 propellants. This transition took many years, in particular due to the development of new seal materials compatible with these new propellants.

[0007] Today, it turns out that HFA-134a and / or HFA-227 gases are also harmful to the environment, and it is necessary to replace them with gases that are less harmful to the environment, such as HFA-152a (1,1-difluoroethane), HFO-1234ze (1,3,3,3-tetrafluoropropene) or HFO-1234yf (2,3,3,3-tetrafluoropropene).

[0008] However, once again this replacement has a significant impact on the operation and reliability of the metering valves, in particular on the metering.

[0009] Thus, for an active ingredient suspended in the propellant gas HFA-152a in aerosol form, dose problems manifest themselves as follows: a higher dosage at the start of use of the device and a lower one at the end of use.

[0010] This problem is mainly linked to the sedimentation speed of the particles, which is faster in HFA-152a, HFO-1234ze and HFO-1234yf than in HFA-134a and HFA-227.

[0011] This difference in sedimentation speed is explained by the difference in density between the particles of the active ingredient (approx. 1.40 g / cm3) and the different propellant gases.Indeed, while the HFA-134a and HFA-227 gases under pressure have liquid densities at 21°C very close or even identical to those of the active ingredient particles in suspension (1.40 g / cm3 for HFA-227 and 1.22 g / cm3 for HFA-134a), the HFA-152a gas under pressure has a liquid density at 21°C of 0.91 g / cm3, with therefore a very significant difference compared to the density of the active ingredient particles, the HFO-1234yf gas under pressure has a liquid density at 21°C of 1.11 g / cm3, with therefore a significant difference compared to the density of the active ingredient particles, and the HFO-1234ze gas under pressure has a liquid density at 21°C of 1.17 g / cm3, with therefore also a substantial difference compared to the density of the active ingredient particles (sources for the densities of the gases propellants: NIST (National Institute of Standards and Technology) & Honeywell). .

[0012] To overcome this difference, the addition of excipient(s), such as a surfactant, may be useful, but not sufficient.

[0013] The present invention aims to improve metering valves of the non-priming type, that is to say those in which the metering chamber is not sealed in the rest position of the valve, when they are used with propellant gases that are less harmful to the environment.

[0014] The present invention aims in particular to provide a device improving the consistency of the dosage between the start and the end of use of the device.

[0015] The present invention also aims to provide a device for which the variations in dosage between the start and the end of use of the device remain within an acceptable range.

[0016] The present invention also aims to provide a device which is simple and inexpensive to manufacture and assemble, and which operates reliably.

[0017] The present invention therefore relates to a device for dispensing a fluid product comprising a metering valve mounted on a reservoir containing at least one active ingredient suspended in a pressurized propellant gas whose liquid density at 21°C is less than or equal to 1.20 g / cm3, said metering valve comprising a valve body containing a metering chamber, and a valve sliding axially in said valve body between a rest position and a dispensing position, to dispense the contents of said metering chamber, said metering chamber being, in the rest position of the valve, connected to said reservoir, to allow the filling of the metering chamber by gravity when, in the rest position of the valve, the valve is in an inverted position with the metering chamber arranged below the reservoir, and to allow the emptying of said metering chamber by gravity when, in the rest position of the valve, the valve is in an upright position with the metering chamber arranged above the reservoir, said valve body comprising at least one fluid passage opening, defining a passage surface SI connecting said reservoir to the interior of said valve body, said passage surface SI being greater than or equal to 20 mm2 and less than or equal to 100 mm2.

[0018] Advantageously, said passage surface SI is greater than or equal to 25 mm2 and less than or equal to 75 mm2, in particular less than or equal to 60 mm2.

[0019] Advantageously, said valve comprises a collar defining with the valve body a first passage volume VI, said first passage volume VI being greater than or equal to 10 mm3 and less than or equal to 30 mm3.

[0020] Advantageously, said first passage volume V1 is greater than or equal to 15 mm3 and less than or equal to 20 mm3.

[0021] Advantageously, said metering chamber is defined between a valve seal and a chamber seal, said chamber seal forming the inlet of said metering chamber and defining with said valve a second passage volume V2 which is maximum in the rest position of the valve and zero in the dispensing position of the valve, said second passage volume V2 being greater than or equal to 2 mm3 and less than or equal to 10 mm3.

[0022] Advantageously, said second passage volume V2 is greater than or equal to 3 mm3 and less than or equal to 5 mm3.

[0023] Advantageously, said valve body comprises three fluid passage openings.

[0024] Advantageously, said at least one fluid passage opening is in the form of a longitudinal slot.

[0025] Advantageously, said propellant gas comprises HFA-152a (1,1-difluoroethane) and / or HFO-1234ze (1,3,3,3-tetrafluoropropene) and / or HFO-1234yf (2,3,3,3-tetrafluoropropene).

[0026] Advantageously, said at least one active ingredient comprises salbutamol, in base or salt form, in particular salbutamol sulfate.

[0027] Advantageously, said at least one active ingredient is micronized.

[0028] The present invention also relates to the use of a device as described above for dispensing a pharmaceutical formulation comprising at least one active ingredient suspended in a pressurized propellant gas having a liquid density at 21°C less than or equal to 1.20 g / cm3.

[0029] Advantageously, said at least one active ingredient comprises salbutamol, in salt or base form.

[0030] Advantageously, said propellant gas comprises HFA-152a and / or HFO-1234ze and / or HFO-1234yf.

[0031] Advantageously, said active ingredient is salbutamol sulfate and said propellant gas is HFA-152a.

[0032] These and other features and advantages of the present invention will become more clearly apparent from the following detailed description thereof, given with reference to the accompanying drawings, given as non-limiting examples, and in which

[0033] [Fig.l] [Fig.l] is a schematic cross-sectional view of a device comprising a dispensing valve without priming, according to an advantageous embodiment, in the rest position,

[0034] [Fig.2] [Fig.2] is a schematic cross-sectional view of the device of the [Fig.l], in the valve distribution position,

[0035] [Fig.3] [Fig.3] is a detail view of the valve of [Fig.l], showing a fluid passage opening in the valve body forming part of the passage surface SI,

[0036] [Fig.4] [Fig.4] is a detail view of [Fig.l], showing a first volume of passage VI at the valve collar,

[0037] [Fig.5] [Fig.5] is a detail view of [Fig.l], showing a second volume of passage V2 at the level of the inlet of the dosing chamber, and

[0038] [Fig.6] Figures 6 to 8 are graphs comparing the doses of active ingredient of a device according to the invention with those of a reference device, respectively at the end of an equilibration period of at least one week after filling called T0, after one month of storage and after three months of storage.

[0039] [Fig.7] cf [Fig.6]

[0040] [Fig.8] cf [Fig.6]

[0041] [Fig.l] represents the valve in the upright storage position, i.e. the position in which the dosing chamber is arranged above the reservoir, while [Fig.2] represents the valve in the inverted use position, i.e. the position in which the dosing chamber is arranged below the reservoir.

[0042] The priming-free metering valve shown in the figures comprises a valve body 10. Inside said valve body 10, a valve 30 slides between a rest position, which is that shown in [Fig.l], and a position of distribution, shown in [Fig.2], in which the valve 30 is pressed inside the valve body 10.

[0043] This valve is intended to be assembled on a tank 1, preferably by means of a fixing element 5, which can be a crimped, screwed or snap-on cap, and advantageously with the interposition of a neck seal 6.

[0044] Optionally, a ring 4 may be assembled around the valve body, in particular to reduce the dead volume in the inverted position and to limit the contact of the fluid product with the neck seal. Conversely, it is also possible to provide for the absence of such a ring to increase the volume around the valve body.

[0045] The valve 30 is biased towards its rest position by a spring 8, which is arranged in the valve body 10 and which cooperates on the one hand with this valve body 10, and on the other hand with a radial collar 320 of the valve. This radial collar 320 slides in the valve body 10 when the valve 30 moves between its rest and distribution positions. Between the valve body 10 and the collar 320, a first fluid passage volume VI is defined. In the example of the figures, the collar 320 is formed by four radial studs arranged at 90° to each other, but other implementations are possible, for example a collar extending over the entire periphery of the valve.

[0046] A metering chamber 20 is defined within the valve body 10, said valve 30 sliding within said metering chamber 20 to allow the contents thereof to be dispensed when the valve is actuated. The metering chamber 20 is preferably defined between two annular seals, a valve seal 21 and a chamber seal 22, in a well-known manner.

[0047] The valve 30 comprises an outlet orifice 301 connected to a radial channel 302, which is arranged in the metering chamber 20 when the valve 30 is in the dispensing position.

[0048] The valve 30 can be made in two parts, namely an upper part 31 (also called valve top) and a lower part 32 (also called valve bottom). The lower part 32 is in this embodiment assembled inside the upper part 31.

[0049] As can be seen in the figures, when the valve 30 is in the rest position, the metering chamber 20 is permanently connected to the reservoir, since the metering chamber 20 is not sealed in this rest position of the valve 30. Thus, at the inlet of the metering chamber 20, at the chamber seal 22, a second passage volume V2 is defined which is maximum in the rest position of the valve 30, and which is completely sealed in the dispensing position of the valve 30.

[0050] The valve body 10 comprises one or more fluid passage openings 11, advantageously in the form of longitudinal slots, preferably three slots. These passage openings 11 together define a passage surface SI connecting the reservoir 1 to the interior of the valve body 10.

[0051] When the valve is stored in the upright position of [Fig.l], the metering chamber 20 empties, and when the user wishes to use the valve, he returns it to the inverted position of [Fig.2], so that the metering chamber 20 will fill by gravity. This emptying and filling occurs via a fluid passage which includes the passage surface SI, the first passage volume VI and the second passage volume V2.

[0052] The priming-free metering valves of the prior art, when used with at least one active ingredient suspended with the new propellant gases, in particular HFA-152a and / or HFO-1234ze and / or HFO-1234yf, i.e. pressurized propellant gases whose liquid density at 21°C is less than or equal to 1.20 g / cm3, have a drawback in terms of the metering which decreases in the doses emitted as the valve is used successively. In other words, the first doses dispensed are larger than the last doses, this difference being sometimes substantial and therefore disadvantageous when the dispensing device is intended to dispense constant doses of active ingredient. The problem is in fact not only the variation in the doses, but the extent of this variation, and it is this variation which it is desirable to minimize.

[0053] The inventors have surprisingly noticed that this specific drawback of non-priming valves used with propellant gases whose density is lower than the density of the active ingredient particles, such as HFA-152a and / or HFO-1234ze and / or HFO-1234yf, can be significantly reduced by modifying, in particular by increasing, the fluid passage between the reservoir 1 and the metering chamber 20.

[0054] Thus, according to the invention, the passage surface SI of the passage openings 11 of the valve body 10 is greater than or equal to 20 mm2, advantageously greater than or equal to 25 mm2.

[0055] Of course, this passage surface SI cannot be infinite, and advantageously, it should be less than 100 mm2, advantageously less than 75 mm2, preferably less than 60 mm2.

[0056] Furthermore, it is also advantageous to increase the first and second passage volumes VI and V2.

[0057] Thus, the first passage volume V1 around the collar 320 is advantageously greater than or equal to 10 mm3, preferably greater than 15 mm3.

[0058] Advantageously, this first passage volume V1 is less than 30 mm3, preferably less than 20 mm3.

[0059] Furthermore, the second passage volume V2 at the inlet of the metering chamber 20 is advantageously greater than or equal to 2 mm3, preferably greater than 3 mm3.

[0060] Advantageously, this second passage volume V2 is less than 10 mm3, preferably less than 5 mm3.

[0061] Various comparative tests were carried out to demonstrate the effectiveness of the invention and to evaluate the dimensional characteristics of the different fluid passages.

[0062] In these tests, a non-priming valve of the state of the art, in this case a valve produced according to document WO2014195616A1, called Primeless valve ref, was compared with a non-priming valve according to the present invention, called Primeless 3-slot valve. The Primeless valve ref had a flow area SI equal to approx. 0.40 mm2. The Primeless 3-slot valve had a fluid flow area SI equal to approx. 27 mm2, formed by three longitudinal slits as a fluid flow opening 11.

[0063] Both valves were tested with a micronized salbutamol salt suspended in HFA-152a, in particular with a pharmaceutical formulation consisting of pharmaceutically acceptable salbutamol sulfate, 1,1-difluoroethane (HFA-152a), and ethanol.

[0064] The delivered doses of salbutamol were quantified at individual doses 1, 2, 3, 198, 199 and 200, therefore at the start and end of use of the devices.

[0065] The graphs in Figures 6 to 8 illustrate the impact of the increase in the flow area SI on the dosages, respectively at T0 (after equilibration following filling of the device), T1 (after one month of stability after T0) and T3 (after three months of stability after T0), under respective temperature and relative humidity conditions of 40°C and 75% which comply with the guidelines of the International Council for Harmonisation for Pharmaceutical Quality (ICH Q1 Stability Guidelines).

[0066] It is noted that the doses of the reference valve are at least partially outside the desired ranges, in this case + / - 35% of the target delivered dose of 90 pg, advantageously + / - 25% of the target delivered dose of 90 pg.

[0067] On the contrary, with the valve according to the invention, all doses are within the desired range of + / - 35%, and even within the preferred range of + / - 25%.

[0068] These results are all the more surprising since they were obtained with a pharmaceutical formulation which does not include any surfactant, whereas surfactants are known to be compounds whose role is to help disperse the particles of active ingredient in the propellant gas.

[0069] Similar tests have been carried out with other formulations, in particular with the addition of a surfactant such as polyethylene glycol in the presence of ethanol, and the results have always been similar. Similarly, other molecules, in particular in micronized form, have also given similar results.

[0070] Although the present invention has been described with reference to one embodiment, it is understood that it is not limited by the examples described. On the contrary, those skilled in the art can make any useful modifications thereto without departing from the scope of the present invention as defined by the appended claims.

Claims

1.

2. Claims Fluid product dispensing device characterized in that it comprises a metering valve mounted on a reservoir (1) containing at least one active ingredient suspended in a pressurized propellant gas whose liquid density at 21°C is less than or equal to 1.20 g / cm3, said metering valve comprising a valve body (10) containing a metering chamber (20), and a valve (30) sliding axially in said valve body (10) between a rest position and a dispensing position, to dispense the contents of said metering chamber (20), said metering chamber (20) being, in the rest position of the valve (30), connected to said reservoir (1), to allow the filling of the metering chamber (20) by gravity when, in the rest position of the valve (30), the valve is in an inverted position with the metering chamber (20) arranged below the reservoir, and to allow the emptying of said metering chamber (20) by gravity when,in the rest position of the valve (30), the valve is in an upright position with the metering chamber (20) arranged above the reservoir, said valve body (10) comprising at least one fluid passage opening (11), defining a passage surface SI connecting said reservoir (1) to the interior of said valve body (10), said passage surface SI being greater than or equal to 20 mm2 and less than or equal to 100 mm2, said valve (30) comprising a collar (320) defining with the valve body (10) a first passage volume VI, said first passage volume VI being greater than or equal to 10 mm3 and less than or equal to 30 mm3, said metering chamber (20) being defined between a valve seal (21) and a chamber seal (22),said chamber seal (22) forming the inlet of said metering chamber (20) and defining with said valve (30) a second passage volume V2 which is maximum in the rest position of the valve (30) and zero in the dispensing position of the valve (30), said second passage volume V2 being greater than or equal to 2 mm3 and less than or equal to 10 mm3., Device according to claim 1, in which said passage surface SI is greater than or equal to 25 mm2 and less than or equal to 75 mm2, in particular less than or equal to 60 mm2.

3. Device according to claim 1 or 2, wherein said first passage volume VI is greater than or equal to 15 mm3 and less than or equal to 20 mm3.

4. Device according to any one of the preceding claims, wherein said second passage volume V2 is greater than or equal to 3 mm3 and less than or equal to 5 mm3.

5. Device according to any one of the preceding claims, wherein said valve body (10) comprises three fluid passage openings (11).

6. Device according to any one of the preceding claims, wherein said at least one fluid passage opening (11) is in the form of a longitudinal slot.

7. A device according to any preceding claim, wherein said propellant gas comprises HFA-152a (1,1-difluoroethane) and / or HFO-1234ze (1,3,3,3-tetrafluoropropene) and / or HFO-1234yf (2,3,3,3-tetrafluoropropene).

8. Device according to any one of the preceding claims, in which said at least one active ingredient comprises salbutamol, in base or salt form, in particular salbutamol sulfate.

9. Device according to any one of the preceding claims, wherein said at least one active ingredient is micronized.

10. Use of a device according to any one of claims 1 to 9 for dispensing a pharmaceutical formulation comprising at least one active ingredient suspended in a pressurized propellant gas having a liquid density at 21°C less than or equal to 1.20 g / cm3.

11. Use according to claim 10, wherein said at least one active ingredient comprises salbutamol, in salt or base form.

12. Use according to claim 10 or 11, wherein said propellant gas comprises HFA-152a and / or HFO-1234ze and / or HFO-1234yf.

13. Use according to any one of claims 10 to 12, wherein said active ingredient is salbutamol sulfate and said propellant gas is HFA-152a. * * *

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