MXPA01008554A - Slow spray metered dose inhaler - Google Patents

Abstract

A pressurised metered dose inhaler having an actuator constructed and arranged so as to inhibit airflow due to patient inhalation in the vicinity of the orifice of the nozzle block when the valve stem is in its dispensing position. This design reduces unwanted oropharyngeal deposition of medicament and increases the relative amount of medicament to the lung.

Description

INHALER OF SLOW DOSE OF MEASURED DOSE FIELD OF THE INVENTION The present invention relates to an inhaler for medicament and in particular to an inhaler for transferring to the respiratory system of a patient a metered dose of a medicament contained in a pressurized dispensing canister. BACKGROUND OF THE INVENTION In metered dose inhalers, the aerosol stream consisting of the liquid propellant and the medicament from a pressurized dispensing canister is fired into a chamber towards a mouthpiece of the inhaler into the airspace that allows the air flow that travels in the same direction through the openings to the outside air, In devices known to be operated a user inhales through a mouthpiece of the inhaler and creates an air flow through the chamber from the air inlets that are generally part of the inhaler located upstream of the mouthpiece. After actuation, the medicament is then released in this air flow at a point between the air inlets and the nozzle in such a way that it travels in the same direction to the air flow.

Typically in those devices there is restriction in the air flow that can be created by a user of the device and because the medicament is fired in the air flow in the same direction as the air flow, the effect is that the Medications may be traveling at fairly substantial speeds, for example greater than 40 m / s when they reach the mouthpiece. Since inhalers of this type are normally designed to be the most practically small for the convenience of the user, the distance between the point at which the device fires at the air flow and the patient's mouth is generally very small. so there is little distance to reduce the inertia of the drug particles with the result that the particles can impetrate and deposit in the oropharynx and not be carried by the inhaled air to the lungs. This is usually quite undesirable, since the drugs were designed to be transported to the respiratory system and may not have an appropriate effect when they are deposited in the oropharynx and allowed to enter the digestive tract. In an effort to solve this problem, devices have been produced in which the medication is fired into a retention volume, commonly called a spacer, which allows the speed of the medication to be reduced and thus allows the evaporation of a little propellant. Spacers can improve the performance of a metered dose inhaler by reducing oropharyngeal deposition, see S.P. Ne an & S. Clarke, Chest.vol. 103 (5) pages. 1442-1446 (1993) Bronchodi lat or Delivery From Gentehaler, A New Low-Velocity Pressurized Aerosol Inhaler and S.P. Newman, A.R. Clark, N. Talee & S.W. Clarke, Thorax, col. 44, pgs. 706-710 (1989), Pressurized aerosol deposition in the human lung with and without a "open" spacer device. However, those devices with a retention volume and other spacer devices tend to have significantly larger dimensions than conventional metered dose inhalers and are therefore less convenient and attractive to users. Several attempts have been made to modify the spray characteristics of the inhalers. GB-A-2279879 discloses an inhaler in which the air inlets are positioned in such a way that during inhalation an air flow of such mold is created having a component directed from the nozzle towards the spray in spray. The reverse air flow component is intended to create turbulence and reduce the velocity of drug particles. WO93 / 05837 and US-A-4972830 describe inhalers in which the passage that directs the pressurized medicament from the canister to the chamber has particular configurations to reduce the spray speed and improve the dispersion of the medicament in the air flow. EP-A-0412648 discloses an inhaler in which a diverter in the form of a truncated cone with a small hole is placed in the path of the spray before the nozzle. The aerosol droplets are said to pass predominantly through the small hole, they decelerate and are inhaled while the propellant gas is deviated predominantly from the nozzle out of the inhaler. It is known to modify the flow of air through an inhaler to achieve particular effects. WO93 / 09830 discloses an inhaler that is constructed and arranged to prevent inhalation through the device before the dose is triggered. The object of the arrangement is to synchronize the inhalation and trigger the dose to ensure that the dose is administered during inhalation. US-A-5758639 discloses an inhaler that includes an air port, such that during inhalation the air flow through the port activates a generation of auditory or visual signal, such as a solid or flag, which indicates to the user that the user is inhaling and that the conditions are appropriate for the administration of the medication. Similarly for intranasal inhalers it is desirable to reduce the spray speed in the interest of patient comfort and effectiveness. SUMMARY OF THE INVENTION The present invention provides alternative constructions of an inhaler that reduces the velocity of the spray coming out of the nasal tip or adapter. In accordance with the present invention there is provided an inhaler for medicament which consists of an aerosol canister containing a pressurized medicament formulation equipped with a metered dose dispensing valve having a valve rod that moves between dispensing and dispensing portions. no dispensing, an actuator consisting of a housing adapted to receive the aerosol container and defining a chamber having one or more air inlets and a port for the patient in the form of a nozzle or nasal adapter, a nozzle block adapted to receive the stem of the valve of the distributor valve, the nozzle block consists of a passage in communication with the valve stem and ending in a hole to direct the medicament from the valve stem towards the chamber, in which the actuator is constructed and arranged to inhibit airflow induced by the patient in the vicinity of the tober block hole a when the valve stem is in its distribution position. The inhaler of the invention can be constructed in such a way that the air flow due to inhalation of the patient is prevented or reduced in the vicinity of the simple orifice or only during the distribution of the medicament from the valve. Any arrangement has the effect of substantially reducing the velocity of the dew emitted as compared to an inhaler that allows free flow of air in the vicinity of the nozzle block during drug delivery. It is possible to modify existing pressure and aspiration inhalers to prevent air flow by providing an adequate gasket. It has been found that the velocity of an aerosol spray from a metered dose inhaler is significantly influenced by the presence of an open conduit in the vicinity of the nozzle through which the spray exits. The spray comes out of the nozzle as a high-speed current that creates regions of low pressure. The ability of the free-flowing air entering through the air vents to fill the low-pressure regions influences the velocity of the dew emitted. Allowing a free flow of air in the vicinity of the nozzle, such as in standard pressure and aspirator inhalers in which the patient breathes through the nozzle and an air flow is established around the canister and nozzle to the nozzle, the dew emitted maintains a high speed. If the actuator is sealed to the outside air flow in the vicinity of the nozzle, the low pressure regions can not be immediately occupied by the surrounding air and the low pressure regions exert a retardant influence on the current emanating from the nozzle, causing the current to lose speed. It has been found that free-flowing air in the vicinity of the nozzle when the spray is generated significantly reduces the velocity of the dew emitted and the spray force of the nozzle., resulting in an extremely soft wake of low velocity spray. The vicinity of the orifice includes all sides upstream of the permanent or temporary closure behind the nozzle block and downstream at the first communication with the outside atmosphere. This is during the distribution there is no communication with the outside atmosphere for the region surrounding the hole of the nozzle block. There is no communication with the outside atmosphere through the upstream air inlets to the nozzle block orifice and there is no communication with the outside atmosphere downstream of the nozzle block orifice for a sufficient distance to allow the spray stream develop enough turbulence to stop your moment downstream. For example, the current leaving the hole from 0.30mm to 0.50 mm would not be in communication with the outside atmosphere through the upstream air inlets and the current would be in communication with the outside air extra absorbing the device in a distance downstream in relation to the orifice of 4 to 6 cm. The location downstream of the hole in which the outside air is introduced to the device can vary from 0 to 1 | 5 cm depending on the diameter of the orifice and the diameter of the nozzle. Radio testing has revealed that when the airflow in the vicinity of the nozzle is prevented or restricted, the flow of the spray becomes turbulent within the chamber. The turbulent zone is generally formed between about -3 to 5 cm from the nozzle for a nozzle orifice of about 0.30 mm. The high degree of turbulence causes a large reduction in the linear velocity of the spray as well as an increase in the deposition of the medicament particles on the wall of the chamber. If the chamber and nozzle are large enough to include this turbulent zone, the result is a significant reduction in the kinetic energy of the current delivered to the patient. Preferably, the actuator is constructed in such a way that the distance from the nozzle to the nozzle is approximately 1 to 15 cm, preferably 4 to 6 cm, with a chamber / nozzle diameter of 1 to 4 cm, 0.5 to 1 cm in the case of a nasal adapter. The actuator must have air intakes that allow the patient to inhale through the patient port without encountering significant resistance since the patient may have breathing difficulties when taking the medication, for example during an asthma attack. However, the air intakes, for example in the nozzle, should not concentrate the air flow in an area too narrow, as this would give a high velocity to the incoming air that would divert the spray to the wall of the nozzle opposite to the the entrance of air. In one embodiment of the invention, the air inlets are placed downstream of the nozzle, in the region of the turbulent zone and / or downstream of the turbulent zone. The placement and direction of the air inlets can also affect the deposition of the medication inside the chamber and the mouthpiece. In one arrangement the air inlets consist of a series of orifices, within or below the turbulent zone adjacent to the nozzle directing air perpendicular to the aerosol stream. In a second arrangement the air inlets are directed towards the exit of the nozzle to introduce an envelope of air around the aerosol stream, parallel to the aerosol stream. In a third location the air inlets are optionally placed interdispersed with baffles in the wall of the chamber, to direct the air in the turbulent zone to mix air with the aerosol stream. In a fourth mode the air inlets are placed at the downstream or downstream end of the turbulent zone and direct the air back to the turbulent zone. In another arrangement a nozzle is constructed of a porous material to allow a multiplicity of finely divided air vents to provide an air flow over a larger surface. The air flow diffused through the nozzle also tends to keep the stream of the formulation away from the nozzle wall, reducing the deposition of medication on the walls. In a second embodiment of the invention the actuator may present air inlets upstream of or in the vicinity of the nozzle but the air inlets are blocked when the valve is triggered to release the spray of spray. The air inlets open after the dew has been released at the moment the speed of the current will have been reduced and the turbulent zone will be formed. After inhalation, an air flow will be established from the air inlets to the nozzle that includes the residual aerosol spray. The actuator may include additional air inlets under the nozzle, as described above with respect to the first embodiment. These downstream air inlets do not need to be closed during aerosol spray release. A third mode uses a porous membrane to introduce the air in or under the turbulent zone; The advantage of the membrane is that air is introduced more evenly and diffusely around the circumference of the spray, thus acting as a buffer between the turbulent flow and the wall. The effect is to reduce the predisposition of the medication to be deposited on the device. The membrane can optionally be protected from dust or by contact with the user's lips by an additional part of the nozzle. This mode can be used in combination with mode 1 or 2. Additionally this mode can be incorporated without restricting or preventing the flow of air in the vicinity of the nozzle. For certain medications it is particularly desirable to reduce in contract between the medication and parts of the body for which it is not intended.

For example, drug residues deposited on the internal surfaces of the actuators can be transported by the fingers to other parts of the body. A fourth embodiment of the invention incorporates a diverter to allow the spray to pass, limiting the patient's access to the internal surface of the actuator. A fifth embodiment of the invention is configured for intranasal administration. It is known that the size of the holes in the nozzle can affect the spray characteristics. The smaller orifices tend to produce aerosols with reduced droplet sizes that lead to a better respirable fraction. However, smaller orifices are more difficult to manufacture. The actuator of the invention significantly reduces the spray speed regardless of the size of the hole. It has been shown to reduce oropharyngeal deposition with orifice in the range of 0.03 to 0.07 cm and the deposition for those two sizes was found to not differ significantly. BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described with reference to the accompanying drawings in which: Figure 1 represents a cross section through an inhaler according to an embodiment of the invention. Figure 2 represents a cross-section through an inhaler according to a second embodiment of the invention. Figure 3 represents a diagramatic cross section of a portion of an inhaler according to another embodiment of the invention. Figure 4 represents a partial diagramatic cross section of another inhaler according to the invention. Figures 5a, 5b and 5c represent a cross section of another inhaler according to the invention. Figures 6 to 9 represent cross-sectional views of other inhalers according to the invention. Figures 10 (a) and (b) represents a cross-sectional view of another inhaler according to the invention in its firing and rest positions respectively. Figure 11 shows a cross-sectional view of another inhaler according to the invention in its firing position. Figures 11 (a) to 11 (c) illustrate alternative diverters for your nozzle. Figures 12a and b represent a perspective view and a cross-sectional view of a nasal inhaler according to the invention. DETAILED DESCRIPTION The inhaler of Figure 1 consists of an aerosol can (2) equipped with a metered dose distributor valve (4) having a valve stem (6). The actuator, generally shown with (8) consists of a housing (19) that receives the aerosol container (2), a chamber (12) and a nozzle (14). A nozzle block (16) receives the valve stem (6) and has a passage (not shown) ending in a hole (18) which directs the spray from the aerosol valve to the chamber. The housing consists of solid walls (20) in the vicinity of the nozzle block such that there can not be an air flow through the device in the vicinity of the orifice. The air inlet passages (22) are positioned towards the end of the chamber (12) and are directed towards the nozzle (14). When the aerosol valve is triggered, a metered dose of the aerosol formulation leaves the orifice (18) towards the chamber (14). There is no air flow in the vicinity of the hole (18).

Consequently, the spray decelerates rapidly and a turbulent zone is formed, generally shown by the curved lines inside the chamber (12). As the patient breathes through the nozzle (14) the air passes through the inlets (22) toward the nozzle (14) forming an air envelope around the aerosol spray formulation. The inhaler provides a substantially reduced deposition in the patient's oropharynx compared to a standard pressure and aspiration inhaler without unduly compromising the respirable fraction. Figure 2 of the accompanying drawings illustrate a second embodiment of the invention which is similar to Figure 1 and similar numbers represent similar parts. The difference in mode shown in Figure 2 is that the nozzle (14) has a bulb-shaped configuration (24) to provide an increase in the cross-sectional area of the nozzle below the turbulent zone followed by a reduction in the transverse area at the end downstream of the nozzle. The arrangement of the air inlets is similar to that shown in figure 1, the bulb configuration acts in a similar way to the conventional spacer. Figure 3 is a diagrammatic cross section through a portion of an inhaler having an alternative construction of the air inlets. In this embodiment, the air inlets (30) are placed downstream of the nozzle block and have associated deviators (32) such that the incoming air deviates from the turbulent zone of the aerosol spray shown by the curved lines within the camera (12). Air inlets and diverters can extend into the circumference of the chamber or can be placed towards the bottom of the chamber. The deviators can continue along the entire length of the chamber to the nozzle to facilitate turbulence of the air flow. Figure 4 of the accompanying drawings is a diagrammatic cross section of a portion of an inhaler according to the invention. The end downstream of the chamber is formed as a venturi (34) and the air inlet ports (36) are positioned in such a way that the air enters in a direction towards the turbulent zone. The aerosol spray expands through the venturi as it reaches the nozzle (14). l Figures 5a to 5c represent a cross section through an alternative inhaler according to the invention. In this embodiment, when the valve (4) is not in its distribution position, the air inlet ports (40) formed between the container (2) and the housing (10) are opened (Figure 5a). When the valve (4) is in its dispensing position caused by moving the container (2) relative to the valve stem (6) (Figure 5b), the seal 42 around the container (2) closes the inlet ports of the valve (2). air (40). Thus during firing of the aerosol spray, there is no air flow in the vicinity of the orifice (18) and the spray will decelerate and form a turbulent zone within the chamber (12) shown by curved lines. Then, the patient releases the container (2) that returns the valve to the non-dispensing position (figure 5c) and during the inhalation at the nozzle (154) an air flow is established through the air inlets (40) to the mouthpiece (14) by means of the chamber (12) thus introducing the medicament into the inspired air. The inhaler of figure 6 is based on the inhaler of figure 5 and incorporates additional air inlets 22) of the type described in figure 1. The inhaler of figure 7 is based on the inhaler of figure 5 and incorporates a mouthpiece (14) having a bulb-shaped configuration (24) and air inlets (22) of the type described in figure 2. The inhaler of figure 8 is based on the inhaler of figure 5 and incorporates air inlets in the shape of a microporous membrane (50) that is held downstream of the turbulent zone adjacent to the nozzle (14). The arrangement provides a multiplicity of finely divided air inlets which, after inhaling through the nozzle, create a diffuse air flow that keeps the emitted current away from the nozzle wall. The porous membrane material (50) should not significantly impede the ability of the patient to inhale through the device. A suitable material is the Whatmann filter paper no. 4; but other materials may be used, such as those used in cylindrical air filters or membrane filters, or those formed by sintering polymers. A preferred porous membrane material has a cylindrical shape made by fusing small polypropylene granules together. The inhaler of Figure 9 is similar to that of Figure 5, except that the air inlet ports (54) are closed between the flat surface of the valve ferrule (56) and a parallel edge (58) inside the actuator. , by means of a seal (60) when the inhaler is not in its distribution position. Figure 11 shows a similar modality to figure 10 with a diverter (62) inserted. The diverter can be part of a nozzle component (14) like that of figures 6 to 9.

Alternatively, it can be part of a mouthpiece (64) that provides an air envelope that emerges at the downstream end of the inhaler. The person skilled in the art will also appreciate that the nozzle (64) can replace the nozzle (14) in figures 6 to 9. The diverter is in the form of a thin disc defining a plurality of circular passages (65). Preferably there is a large number of circular passages and their accumulated area forms a substantial proportion of the disk area as illustrated in FIG. The nozzle (64) has a plurality of passages (66) parallel to its axis and placed across its circumference.

Figure 11b shows a component with an alternate diverter consisting of a thin disc with a single circular hole (68). Figure 11c shows another component in which the diverter consists of a disk with two kidney-shaped holes (69). Figures 12a and 12b illustrate an inhaler for nasal administration of drugs. The inhaler (80) consists of a body (82) and a nasal piece (84) that is dimensioned such that it can be inserted into a nostril without being hermetically adjusted. The body (82) has an opening (86) for receiving the valve stem (not shown) from the pressurized aerosol, a hole (88) communicating with a chamber (90) that leads to the nasal piece (84). The valve stem forms a gas-tight seal within the hole (88). During use the nasal piece is inserted into a nostril and the patient inhales while actuating the valve of the pressurized aerosol container. Inhalation does not cause air flow through the inhaler (80) but an air flow is established around the outside of the nasal piece and the medication that comes out of the nasal piece is introduced into a flow of air and is administered to the respiratory system of the patient. The inhalers of the invention that are intended for the pulmonary distribution reduce the oropharyngeal deposition. The preferred inhalers of the present invention are capable of providing improvements both in terms of oropharyngeal and pulmonary deposition. For example, the inhaler of FIG. 8 produces greater pulmonary deposition and less oropharyngeal deposition than the metered dose inhaler provided with a standard actuator distributed under the trade name M3756 of 3M. The inhalers were compared by sealing an upper airway against a plaster and firing air at 30 liters per minute (D.J. Velasquez and B. Gabrio 1998 J. Aerosol Med. 11 (Suppl 1): S23-S28). The aerosol that passes through the airway was collected in a HEPA filter. Both inhalers contained beclomethasone dipropionate formulated as a radiolabelled solution. In the following table, the amount examined by means of radio cintrigraphy in the plaster is designated as "oropharyngeal" and the amount in the plaster is designated as "pulmonary". The inhaler produces a drug particle size equivalent to that produced by the standard inhaler with an average diameter of 1.4 microns.

Another advantage of the inhalers of the invention is that the consequences of poor coordination of inhalation with the actuation of the inhaler are improved compared to the standard inhaler. The uncoordination tests were conducted in a standard inhaler of pressure and inhalation with metered dose and a similar inhaler that had been modified according to the invention to operate in principle as described in figure 1. The inhalers were tested using the described equipment before. A delay of 1 second between the activation of the start of the inhalation resulted in the following change in the regional percentage deposition. Change in the percentage regional deposition

Claims (9)

1. CLAIMS 1. An inhaler for medicaments consisting of an aerosol container containing a pressurized medication formulation equipped with a metered dose distributor valve having a valve stem movable between the non-dispensing and dispensing positions, and an actuator consisting of a housing containing the aerosol container and defining a chamber having one or more air inlets and a patient port in the form of a nasal tip or adapter through which inhalation of the patient generates a air flow and a nozzle block adapted to receive the valve stem of the distributor valve, the nozzle block consists of a passage in communication with the valve stem and ending in a hole to direct the medication from the valve stem to the chamber (12) and the actuator is constructed and positioned to inhibit the air flow in the vicinity of the orifice when the stem of the The valve is in its distributing position, characterized in that the air inlets are positioned near the end of the chamber adjacent the nozzle and / or in the nozzle to inhibit the deposition of the medicament within the chamber and the nozzle.
2. 2. An inhaler according to claim 1 in which the air inlets are directed toward the outlet of the nozzle.
3. 3. An inhaler according to claim 1 in which the air inlets are directed perpendicular to the direction of the orifice.
4. 4. An inhaler according to claim 1, in which the air inlets are directed towards the nozzle block.
5. 5. An inhaler according to claim 2, in which the wall of the chamber and / or the nozzle has diverters to divert the air inside.
6. 6. An inhaler according to claim 1 in which the air inlets consist of a multiplicity of numerous small air channels that serve to provide a large surface area for air to enter the nozzle.
7. 7. An inhaler according to claim 6, in which the air inlets have the shape of a microporous membrane.
8. 8. An inhaler according to claim 7, in which the microporous membrane is protected from contamination and / or contact with the patient's lips by means of a protection.
9. 9. An inhaler according to claim 1, consisting of a diverter in the form of a thin disc defining a plurality of circular passages, configured to reduce direct contact between the medication and the patient other than inhalation.