MXPA97001196A - Inhaler apparatus with optimizac camera - Google Patents

Abstract

The present invention relates to an inhaler device operated on breathing comprising an actuator body, a pressurized medicament dispenser containing medicament in suspension or in solution in propellant media, and medication delivery outlet means through which it is supplied the medicament in response to inhalation of a user, wherein said actuator body actuates said medicament dispenser to deliver a metered dose of medicament contained in the propellant in response to inhalation of the user, said device being characterized in that said output means of medicament supply are provided with an optimization chamber equipped with an embouchure and because said chamber has a volume in the range of approximately 20 ml. up to 200

Description

INHALER FLOWER WITH OPTIMIZATION CRMRRR MEMORY OF THE INVENTION The present invention relates to a medicament dispensing device of the type that is used to dispense discrete quantities of a medicament entrained in a stream of air or drive agent. In particular, the invention has to do with devices of the inhaler type with metered doses that are well known in the art of medicine for the treatment of + or respiratory diseases or asthma. A normal metered dose inhaler consists of three main parts: a container under pressure, an actuator body and a drug delivery outlet. The pressurized container contains a mixture of active drug and propellant and is usually formed from a deeply stretched aluminum cup portion having a lid portion attached thereto leading to the assembly of the metering valve. The assembly of the measuring valve is provided with a protruding stem of the valve which, when used, is inserted as a fitted thrust fitting into the so-called "rod block" in the actuator body. The operation of the inhaler requires the user to apply a compressive force to the closed end of the container. The internal components of the metering valve assembly are provided with springs so that typically a compressive force of between 15 and 30 N is required to operate the device. In response to this compressive force, the container moves axially with respect to the valve stem at a distance sufficient to drive the metering valve and causes a measured quantity of the substance and the propellant to be delivered through the stem of the valve. valve .. and then release it to the mouthpiece through the nozzle in the stem block. A user who inhales through the drug delivery outlet of the device at this point will thus receive a dose of the drug. The use of metered dose inhalers has become increasingly widespread in recent years due to the fact that they allow the patient to administer a precise dose of the medically when required. This is particularly useful for patients whose respiratory difficulties manifest themselves suddenly. One of the problems encountered most frequently with respect to the normal inhaler with metered dose as described above is that the patient has difficulty in coordinating the action of oppressing the aerosol container with the act of inhaling. This can be particularly problematic when the patient is in distress due to a sudden excess of breathing difficulties. It is also difficult for young children to coordinate those actions appropriately. Such problems tend to undermine the effectiveness of self-administration. These difficulties have now been overcome by the introduction of actuators operated on breathing such as those described in the applicant's international patent application No. UO 92/09323. When operating an inhaler under pressure, the propellant stream is explosively dispersed at atmospheric pressure to produce a range of different sizes of small droplets of the propellant containing the drug, either in suspension or possibly in solution. Although the propellant agent in the small droplets tends to evaporate, it causes the small droplets to decrease in size over time, the patient still receives a cloud of small droplets containing the drug of various sizes. The small droplets tend to separate according to their sizes under the influence of gravitational forces and air currents. The smallest droplets, typically 5-6 μ in diameter, pass through the patient's oropharynx to enter the trachea, bronchi, and inferior tracts where they can exert a therapeutic effect. The larger droplets, on the other hand, can be deposited in the patient's oropharynx, due to their different inertial characteristics, having an incision escaped over the normal embouchure of the actuator. Such oropharyngeal sedimentation is inconvenient for many reasons.

For example, the patient may experience an unpleasant taste or a cooling effect, since the small droplets of propellant rapidly evaporate at the contact of the warm mucous membrane. Unwanted sedimentation of certain classes of compounds can cause even inconvenient local side effects, such as corticosteroids that can lead to Candida ("a ta") infections. A satisfactory approach for eliminating the problems caused by sedimentation of large droplets in unwanted areas is the use of so-called "large volume separators". These are deposits having a typical capacity of approximately 750 ml which are adapted at one end to be fixed at the delivery outlet of an inhaler under pressure, with a mouthpiece at the other end for coupling to the user's mouth. Usually, the large volume separator is equipped with a unidirectional valve to prevent the user from exhaling in the separator cavity. In use, the inhaler is operated in the separator cavity, where the aerosol emitted is effectively trapped. Large droplets can either impinge on the walls of the separator or fall to the bottom of the cavity. The patient inhales the aerosol from the separator cavity, consisting of an inhaled cloud of predominantly fine drops that pass with the current of air inhaled to the lungs by virtue of their relative aerodynamic stability.

The patient does not need to inhale simultaneously with the operation of the inhaler; some delay is possible. This eliminates the need for precise coordination of actions and alleviates some of the problems associated with the instantaneous administration of the drug controlled by the patient. However, the means to use the large volume separators is not optimized and vapaion is possible in practical use. Unfortunately, the use of large volume separators introduces a different range of difficulties. The main one among these is the huge size of a large volume separator. You can not carry such a device comfortably in your pocket or in a handbag, so the advantage of the portable that makes metered dose inhalers so attractive by the requirement of the large volume separator is immediately canceled. Also, it is not always possible for particularly weak people or very young children to manipulate the combination of the inhaler and the separator. Such patients therefore require assistance which once again undermines the convenience of the inhaler device. Attempts have been made to solve the above problems with collapsible telescopic separators, but these have only had limited success. In any case, they do not satisfactorily overcome the problem of coordination described at the beginning.

The so-called "tube" separators have been composed as an alternative but have enjoyed only limited success. While they are very compact, their performance as support chambers is inefficient because virtually all of the aerosol is deposited on the walls of the separator in a very short time. The tube separators merely trap some of the large droplets that would otherwise be deposited in the patient's oropharynx and the problem of coordination remains unresolved. Until now, the only effective way to use a combination of tube separator and inhaler-pressurized has required the coordination of the activation of the inhaler with the inhalation of the patient. As explained above, such coordination action is not simple for any category of patient. Some similar considerations apply in relation to dry powder inhalers, where the term "particles" could be used instead of "drops" in the preceding discussion of the devices according to the prior art. It is therefore a goal of the present invention solve the aforementioned coordination problem while facilitating the administration to the patient of an effective dose of the required drug by means of a compact inhaler system. The invention is an inhaler device comprising an actuator body adapted to receive a medication dispenser and medication delivery outlet means through which the medicament is delivered in an air stream in response to user inhalation, characterized in that said delivery means for supplying the medicament is provided with an opti gation chamber equipped with a mouthpiece and that said chamber has a volume in the range of 20 mi to 200 i. Such an arrangement confers the advantage of the large volume separator (without the requirement of coordinating the activation of the inhaler with patient inhalation) by facilitating drug delivery in response to patient inhalation. In addition, the advantages of the tube separator are also present because the inventive arrangement is compact but still allows large droplets or particles to be retained in the aerosol optimization chamber. As indicated above, the drawback of the tube spacers is avoided. There is no need for coordination of inhaler activation and patient inhalation. In one embodiment of the invention, the medicament dispenser is a pressurized container containing the medicament in suspension or in solution in a propellant, and the actuator body is designed to operate the container under pressure in response to inhalation of part of the user. Conveniently, the opti- mization chamber is a separate device that can be coupled by the patient via a push-fit connection to the mouth of a conventional inhaler device operated on breathing. In a particularly preferred modality, the actuator body and the opti- mization chamber are pivotally connected to each other to form a unitary device. In such an arrangement, the opti- mization chamber can be designed to serve as a cover for the medicament delivery of the device, thereby ensuring that the air passage of the device is protected against dirt and other ingress of foreign bodies. The deployment of the opti- mization chamber then opens a passage from the drug delivery outlet of the actuator body to the patient's mouth through the interior of the chamber. Surprisingly, it has been found that the apparatus according to the present invention maintains a high respirable fraction of the dose delivered of the medicament. In relation to the inhaled breathing devices used without any type of separator, the apparatus according to the present invention supplies a respiratory fraction that is at least of the same size. In relation to the normal inhalers used in combination with the large volume separators, the apparatuses according to the present invention provide a significantly larger respirable fraction. The invention will now be described by way of example only with reference to the drawings, in which: Figure 1 is a schematic cross-sectional view through one embodiment of the apparatus according to the present invention; Figure 2 is a graph comparing the performance of an inhaled breathing device that is used alone, a normal inhaler used with a large volume separator, and a device in accordance with the present invention for a medication dose of 100 μg, and Figure 3 is a graph similar to that of Figure 2, which compares the performance of a 250 μg medicine dose. Referring now to Figure 1, a mode of the inhaler apparatus according to the present invention is shown. it consists of an actuator body 20, a pressurized medicament dispenser 40 and an aerosol optimization chamber 60. The actuator body 20 is formed of an upper section 21 and a lower section 22, the lower section 22 having a mouth 23 formed in one piece and a dust cap 24 mounted with a pivot to prevent the entry of dust through the mouthpiece when the appliance is not in use. The upper section 21 accommodates the mechanism for effecting the breath actuation, but in view of the fact that the precise method by which the breath actuation is achieved is not part of the present invention, this feature will not be described in detail herein. . As shown, the upper section 21 includes a series of air inlets 29 to allow air to enter the apiarate in response to patient inhalation. As shown, the actuator body 20 houses a medication dispenser under pressure 40 in the form of an aerosol canister of generally cylindrical shape. The aerosol canister has a rod 41 containing an aerosol dispensing valve (not shown) of conventional design. A support 26 formed on the base of the actuator body 20 is provided with a perforation 27 with such dimensions to form a hermetic seal with the rod 41 of the aerosol can. A shoulder 28 in the bore forms a seat in the for the tip of the rod 41 and helps to keep the aerosol can in position inside the actuator body 20. The nozzle 25 communicates between the bore 27 and the mouth 23. The apparatus is moved away with the dust cover 24 pivoting to the open position to allow attachment of the aerosol optimization chamber 60 to the mouth 23 of the actuator body 20. This is the simplest form of the invention, in which the opti Aerosolization 60 is a separate unit adapted to be connected to the mouth 23 by an interference fit. The opti- mization chamber 60 has its own mouth formation 61 at the end thereof away from the connection to the actuator body 20. In use, the patient inhales through the mouthpiece. 61 of the optimization camera. In response to inhaling the patient, the drive mechanism of the actuator body 20 moves the aerosol can so that its dispensing valve is opened thereby providing a metered dose of medicament entrained in the propellant streams through the nozzle. The measured dose expands explosively in a cloud of small droplets of various sizes that pass to the aerosol optimization chamber 60. Here, large droplets (typically of a diameter greater than 6-7 μm) strike the walls of the camera and are not inhaled by the patient. The smaller drops are relatively aerodynamically stable and are aspirated by the patient. A high proportion of the stabilized cloud is attracted to the trachea, bronchi and lower tracts of the patient where the drug can exert its therapeutic effect. Turning now to Figures 2 and 3, these show the comparative views of various provisions of the inhaler apparatus. The graph of Figure 2 compares the performance of a 100 μg dose of beclomethasone dipropionate (BDP) dispensed through: (A) an inhaled device operated on breathing alone; (B) a normal inhaler used with a large volume separator, and (C) an apparatus in accordance with the present invention. The so-called "stage 1" fraction is the fraction that contains larger droplets with a diameter of 6-7 μrn or more. The "stage 2" fraction is composed of finer droplets and is generally considered by the person skilled in the art as the respirabie fraction, which is the proportion of an inhaler cloud that is most likely associated with the therapeutic activity. . The reactions of step 1 and step 2 were differentiated by a two-stage incident apparatus specified in the British Pharmacopoeia of 1994, which can be used to separate an aerosol cloud based on the size of the droplets. It will be noted that Figure 2 shows that, with the inhaler device operated on breathing that is used alone, the fraction of stage 1 amounts to 50% of the dose delivered. The normal inhaler combined with a large volume separator has a fraction of stage 1 of less than 10%, while the apparatus according to the present invention shows a fraction of stage 1 of about 15%, showing the latter what they are likely to be clinically useful reductions in oropharyngeal sedimentation. However, with reference to the critical fraction of step 2, it can be seen that the inhaler device operated on breathing provides a respiratory fraction of about 402 of the measured dose. The apparatus according to the present invention also shows a high breathable fraction (> 45%), whereas the combination of the normal inhaler and large volume separator shows a respirable fraction of slightly above 30%. For some medications, that would be below the minimum threshold allowed by the British Pharmacopoeia. It should also be kept in mind that the respirable fraction obtained from a large volume separator decreases with time, so that this figure of 30% represents a maximum respirable fraction available to the patient assuming immediate inhalation. The graph of Figure 3 shows a corresponding analysis of a 250 μg dose of beclonetasone dipropionate. This graph showing the observed trends for a dose of 100 μg is accentuated more sharply at higher doses. Not surprisingly, the inhaled inhaler device when replacing unadulterated exhibits a high fraction in stage 1, but supplies a respirable fraction of only 30%. The fraction in stage 1 of the combination of the normal inhaler and the large-volume separator is just over 5%, but the respirable fraction is significantly reduced to a level of less than 20%. In contrast, the apparatus according to the present invention not only maintains a low pressure in stage 1 (21%), but also supplies a breathable fraction of 35%. These figures show that the apparatus according to the present invention give rise to the surprising synergistic effects that are likely to result in significant benefits for the patient. The fact that the device is an inhaler device operated on breathing means that it is capable of providing an accurate and consistent injection of doses when the patient inhales. The injection of the dose can be controlled by the mechanical design of the inhaler-operated device when breathing, for example that occurs at the inhaled air flow rate of 25 1 per minute. Such a drive is fully automatic and reproducible in response to patient inhalation. In addition, the aerosol optimization chamber that fits over the mouth of the actuator body is of sufficiently small size to ensure that the air flow is immediately transmitted to the actuator mechanism of the apparatus. Also, the volume of inhalable air that carries the dose of the medication is within the volume of air inhaled restricted of an asthmatic patient (perhaps 500 mi). In conclusion, the apparatus designed in accordance with the present invention is capable of eliminating a significant proportion of the large droplets of medicament-containing propellants while maintaining the critical respirable fraction of the aerosol containing the therapeutically active portion of the medicament. administered. Both objectives are achieved without requiring the patient to coordinate the activation of the inhaler with inhalation. Although the invention has been described particularly with reference to only a simple embodiment, it will be understood that several modifications are possible. In particular, it will be understood that the inventive principle described herein is equally applicable to dry powder inhalers and devices operated on breathing - subjected to pressure.

Claims (4)

NOVELTY OF THE INVENTION CLAIMS

1. - An inhaler device operated on breathing that consists of an actuator body 20 and an outlet means for dispensing the medication 23 through which the medicament is delivered in response to inhalation of a user, said actuator body being adapted to receive a dispenser of pressurized medicament 40 containing the medicament in suspension or in solution in propellant means, and said actuator body 40 for actuating said medicament dispenser 40 in response to the inhalation of the user, further characterized in that said delivery means for supplying the medicament 23 is provided with an optimization chamber 60 equipped with a mouthpiece 61, and in that said chamber 60 has a volume in the range of 20 rnl to 200 rnl.

2. An inhaler device operated on breathing in accordance with claim 1, further characterized in that the optimation chamber 60 is a separate device coupled by a push-fit connection to said drug delivery outlet means 2

3. 3. - An inhaler device operated on breathing according to claim 1 or 2, further characterized in that the actuator body 20 and the optimization chamber 60 are pivotally connected to each other.

4. A inhaled breathing inhaler device according to any of the preceding claims, further characterized in that the optimization chamber 60 serves as a dust cover for the drug delivery means 23.