Device for dispensing a fluid product
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- APTAR FRANCE SAS
- Filing Date
- 2024-07-06
- Publication Date
- 2026-05-20
AI Technical Summary
Non-priming metering valves used with environmentally friendly propellant gases like HFA-152a, HFO-1234ze, and HFO-1234yf experience significant variations in dosage over time, leading to higher initial doses and lower final doses due to particle sedimentation differences, causing inconsistency and inefficiency.
The design enhances the fluid passage between the reservoir and the metering chamber by increasing the passage surface area and volumes, specifically by defining a passage surface S1 between 20 mm² and 100 mm² and passage volumes V1 and V2, to ensure consistent dosing across the device's lifespan.
This modification maintains dosage consistency within acceptable intervals, reducing variations and ensuring reliable operation, even without the use of surfactants, by optimizing the fluid dynamics and reducing sedimentation effects.
Smart Images
Figure FR2024050921_16012025_PF_FP_ABST
Abstract
Description
[0001] Fluid product dispensing device
[0002] The present invention relates to a fluid product dispensing device comprising a metering valve of the non-priming type.
[0003] So-called metering valves, in which each time the valve is actuation, 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.
[0004] In particular, two types of metering valves are known: on the one hand, so-called retention valves which, after filling the metering chamber, seal it tightly 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 primeless valves or primeless valves.
[0005] For retention valves, there may be a problem of incomplete dose and / or uneven dose delivery, especially if the valve has been stored for some time, which means that the active ingredient is no longer perfectly evenly distributed in the dosing chamber. In addition, these retention valves may have priming problems, which may require the user to operate the valve twice to ensure a complete dose.
[0006] To avoid these problems, non-priming valves allow the metering chamber to fill quickly when the user activates 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 tightly.
[0007] Furthermore, about fifteen years ago, for environmental reasons, the previously used propellants, which were generally CFC-based, were replaced by other propellants, namely HFA-134a and / or HFA-227 propellants. This transition took many years, particularly due to the development of new seal materials compatible with these new propellants.
[0008] 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 less environmentally harmful gases, such as HFA-152a (1,1-difluoroethane), HFO-1234ze (1,3,3,3-tetrafluoropropene) or HFO-1234yf (2,3,3,3-tetrafluoropropene).
[0009] However, once again this replacement has a significant impact on the operation and reliability of the metering valves, particularly on the metering.
[0010] 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 dosage at the end of use.
[0011] This problem is mainly linked to the sedimentation rate of the particles, which is faster in HFA-152a, HFO-1234ze and HFO-1234yf than in HFA-134a and HFA-227.
[0012] This difference in sedimentation rate is explained by the difference in density between the particles of the active ingredient (approx. 1.40 g / cm 3 ) and the various 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 particles of active ingredient in suspension (1.40 g / cm 3 for HFA-227 and 1.22 g / cm 3for HFA-134a), HFA-152a gas under pressure has a liquid density at 21°C of 0.91 g / cm 3 , with therefore a very significant difference compared to the density of the active principle particles, the HFO-1234yf gas under pressure has a liquid density at 21 °C of 1.11 g / cm 3 , 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 / cm 3 , with therefore also a substantial difference compared to the density of the active ingredient particles (sources for the densities of propellant gases: NIST (National Institute of Standards and Technology) & Honeywell).
[0013] To compensate for this difference, the addition of excipient(s), such as a surfactant, can be useful, but is not sufficient.
[0014] Documents FR3114759, GB2402667, W02023039103,
[0015] FR2615124, US2010258757 and EP1545669 describe state-of-the-art valves.
[0016] 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.
[0017] 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.
[0018] 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.
[0019] The present invention also aims to provide a device which is simple and inexpensive to manufacture and assemble, and which operates reliably.
[0020] 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 S1 connecting said reservoir to the interior of said valve body, said passage surface S1 being greater than or equal to 20 mm, 2 and less than or equal to 100 mm 2 .
[0021] Advantageously, said passage surface S1 is greater than or equal to 23 mm 2 and less than or equal to 75 mm 2 , in particular greater than or equal to 24 mm 2 and less than or equal to 60 mm 2 .
[0022] Advantageously, said valve comprises a collar defining with the valve body a first passage volume V1, said first passage volume V1 being greater than or equal to 10 mm. 3 and less than or equal to 30 mm 3 .
[0023] Advantageously, said first passage volume V1 is less than or equal to 17 mm 3 .
[0024] 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 mm 3 and less than or equal to 10 mm 3 .
[0025] Advantageously, said second passage volume V2 is less than or equal to 5 mm 3 .
[0026] Advantageously, said valve body comprises three fluid passage openings.
[0027] Advantageously, said at least one fluid passage opening is in the form of a longitudinal slot.
[0028] 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). Advantageously, said at least one active ingredient comprises salbutamol, in base or salt form, in particular salbutamol sulfate.
[0029] Advantageously, said at least one active ingredient is micronized.
[0030] 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.
[0031] Advantageously, said at least one active ingredient comprises salbutamol, in salt or base form.
[0032] Advantageously, said propellant gas comprises HFA-152a and / or HFO-1234ze and / or HFO-1234yf.
[0033] Advantageously, said active ingredient is salbutamol sulfate and said propellant gas is HFA-152a.
[0034] 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 by way of non-limiting examples, and in which
[0035] Figure 1 is a schematic cross-sectional view of a device comprising a dispensing valve without priming, according to an advantageous embodiment, in the rest position,
[0036] Figure 2 is a schematic cross-sectional view of the device of Figure 1, in the valve dispensing position,
[0037] Figure 3 is a detail view of the valve of Figure 1, showing a fluid passage opening in the valve body forming part of the passage surface S1,
[0038] Figure 4 is a detail view of Figure 1, showing a first passage volume V1 at the level of the valve collar,
[0039] Figure 5 is a detail view of Figure 1, showing a second passage volume V2 at the inlet of the metering chamber, and
[0040] Figures 6 to 8 are graphs which compare 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.
[0041] Figure 1 shows the valve in the upright storage position, i.e. the position in which the dosing chamber is arranged above the tank, while Figure 2 shows the valve in the inverted use position, i.e. the position in which the dosing chamber is arranged below the tank.
[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 Figure 1, and a dispensing position, shown in Figure 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 can 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 V1 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. A metering chamber 20 is defined within the valve body 10, said valve 30 sliding within said metering chamber 20 to allow dispensing of the contents thereof 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.
[0046] The valve 30 has 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.
[0047] 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.
[0048] 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 level of 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.
[0049] 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 S1 connecting the reservoir 1 to the interior of the valve body 10.
[0050] When the valve is stored in the upright position of Figure 1, the metering chamber 20 empties, and when the user wishes to use the valve, he returns it to the inverted position of Figure 2, so that the metering chamber 20 will fill by gravity. This emptying and filling occurs via a fluid passage that includes the passage surface S1, the first passage volume V1 and the second passage volume V2. The prior art non-priming metering valves, 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 / cm 3, have a disadvantage in terms of dosage, 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 can sometimes be substantial and therefore disadvantageous when the dispensing device is intended to dispense constant doses of active ingredient. The problem is not in fact the only variation in doses, but rather the importance of this variation, and it is this variation that it is desirable to minimize.
[0051] 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.
[0052] Thus, according to the invention, the passage surface S1 of the passage openings 11 of the valve body 10 is greater than or equal to 20 mm 2 , advantageously greater than or equal to 23 mm 2 , preferably greater than or equal to 24 mm 2 .
[0053] If the passage surface S1 is reduced too much, in particular to less than 20 mm 2 , we generate a risk of insufficient dosage, with therefore a negative impact on the performance of the device.
[0054] Of course, this passage surface S1 must not be too large, and advantageously, it must be less than 100 mm 2 , advantageously less than 75 mm 2 , preferably less than 60 mm 2 .
[0055] If the passage surface S1 is increased too much, in particular to more than 100 mm 2, there is a risk of the bottom of the valve becoming blocked in the openings forming the passage surface S1, in particular the three slots in the example described. If this blockage is total, the device malfunctions and no dose is dispensed. If this blockage is "partial" (i.e. the bottom of the valve becomes hooked in the slots of the body but the force of the spring is sufficient to remove it), there is an impact on the speed of rise of the valve, and therefore on the user's feelings (sensation of "grip" or "sticking"), and potentially on the performance of the valve. In addition, there would be a risk of weakening the valve body, which could lead to its breakage during the various stages (assembly, filling, testing, etc.).
[0056] Furthermore, it is also advantageous to increase the first and second passage volumes V1 and V2.
[0057] Thus, the first passage volume V1 around the collar 320 is advantageously greater than or equal to 10 mm 3 .
[0058] If the first passage volume V1 is reduced too much, in particular to less than 10 mm 3 , we generate a risk of insufficient dosage, with therefore a negative impact on the performance of the device.
[0059] Advantageously, this first passage volume V1 is less than 30 mm 3 , preferably less than 17 mm 3 .
[0060] If the first passage volume V1 is increased too much, in particular to more than 30 mm 3 , we generate a risk of increasing the possibility of "tilt" of the valve in the valve, with an impact on the interference between the seals and the valve, and therefore an increase in the risk of leaks.
[0061] Furthermore, the second passage volume V2 at the inlet of the metering chamber 20 is advantageously greater than or equal to 2 mm3 .
[0062] If the second passage volume V2 is reduced too much, in particular to less than 2 mm 3 , on the one hand there is a risk of insufficient dosage, with therefore a negative impact on the performance of the device, and on the other hand a risk of increased interference with the valve during actuation, generating an increase in friction, with therefore an impact on the actuation force and dose variability.
[0063] Advantageously, this second passage volume V2 is less than 10 mm 3 , preferably less than 5 mm 3 . If the second passage volume V1 is increased too much, in particular to more than 10 mm 3 , there is a risk of reduced interference with the valve during actuation, which could lead to a risk of leakage.
[0064] Various comparative tests were carried out to demonstrate the effectiveness of the invention and to evaluate the dimensional characteristics of the different fluid passages.
[0065] In these tests, a prior art non-priming valve, in this case a valve made 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 S1 equal to approx. 0.40 mm 2 The Primeless 3-slot valve had a fluid passage area S1 equal to approx. 27 mm 2 , formed by three longitudinal slots as a fluid passage opening 11.
[0066] Both valves were tested with micronized salbutamol salt suspended in HFA-152a, specifically with a pharmaceutical formulation consisting of pharmaceutically acceptable salbutamol sulfate, 1,1-difluoroethane (HFA-152a), and ethanol.
[0067] The delivered doses of salbutamol were quantified at individual doses 1, 2, 3, 198, 199 and 200, therefore at the beginning and end of use of the devices.
[0068] The graphs in Figures 6 to 8 illustrate the impact of the increase in the flow area S1 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 International Council for Harmonisation for Pharmaceutical Quality (ICH Q1 Stability Guidelines).
[0069] It is found 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. In contrast, with the valve according to the invention, all doses are within the desired range of + / - 35%, and even within the preferred range of + / - 25%.
[0070] These results are all the more surprising as 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.
[0071] Similar tests have been carried out with other formulations, notably 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, notably in micronized form, have also given similar results.
[0072] 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
Claims 1. Device for dispensing a fluid product, 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 / cm 3, 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, for dispensing 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 mm, 2 and less than or equal to 100 mm 2 .
2. Device according to claim 1, in which said passage surface S1 is greater than or equal to 23 mm. 2 and less than or equal to 75 mm 2 , in particular greater than or equal to 24 mm 2 and less than or equal to 60 mm 2 .
3. Device according to claim 1 or 2, in which said valve (30) comprises a collar (320) defining with the valve body (10) a first passage volume V1, said first passage volume V1 being greater than or equal to 10 mm 3 and less than or equal to 30 mm 3 .
4. Device according to claim 3, wherein said first passage volume V1 is less than or equal to 17 mm 3 .
5. Device according to any one of the preceding claims, wherein said metering chamber (20) is 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 mm 3 and less than or equal to 10 mm 3 .
6. Device according to claim 5, wherein said second passage volume V2 is less than or equal to 5 mm 3 .
7. Device according to any one of the preceding claims, wherein said valve body (10) comprises three fluid passage openings (11).
8. 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.
9. 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).
10. 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.
11. Device according to any one of the preceding claims, in which said at least one active ingredient is micronized.
12. Use of a device according to any one of claims 1 to 11 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 / cm 3 .
13. Use according to claim 12, wherein said at least one active ingredient comprises salbutamol, in salt or base form.
14. Use according to claim 12 or 13, wherein said propellant gas comprises HFA-152a and / or HFO-1234ze and / or HFO-1234yf.
15. Use according to any one of claims 12 to 14, wherein said active ingredient is salbutamol sulfate and said propellant gas is HFA-152a.