Patent Application
20200206440
The present invention relates to a single-dose dry powder inhaler, especially for capsules containing a medicine.
The present invention further relates to a universal inhaler for administering a single dose of a dry powder, wherein the inhaler is adaptable for use with different dry powders. The present invention further relates to a method for adjusting a universal single-dose dry powder inhaler depending on the physical properties of such a powder.
The effectiveness of an inhalation therapy depends on the appropriate deposition of an inhalation agent in a patient's airways (Sosnowski Tadeusz R., Aerozole Wziewne i Inhalatory, Politechnika Warszawska, Warszawa 2012, ISBN 978-83-906658-7-0). The smaller the particles of a medicinal substance suspended in the inhaled aerosol, the farther they are deposited. Distribution of particles is as follows: particles having diameter less than 10 μm are deposited in a patient's upper airways, particles having diameter in the range from 5 to 10 μm are deposited in the bronchi, whereas particles having diameter in the range from 3 to 4 μm are deposited in the bronchioles. Particles having diameter in the range from 1 to 2 μm are deposited in the alveoli.
Since appropriate deposition of a medicinal substance in a patient's airways determines the effectiveness of an inhalation therapy, selection of an active substance and its carrier for the generation of particles having specific parameters is of significance. In the case of a “dry-powder” type of medicine, obtaining a desired particle fraction distribution is the most important factor.
The effectiveness of the process of breaking down the particles of a medicinal product depends on the forces created as a result of a patient's inspiration. Frequently, the force of a patient's inspiration is too small, and the patient fails to assimilate an appropriate dose of an active substance. Therefore, one aims at implementing structural solutions, whereby the force of a patient's inspiration doesn't have to be too big, allowing an appropriate breaking down the particles of a medication while maintaining suitable parameters of the resulting aerosol. Thus, the deposition efficiency depends on the amount of particle fractions smaller than 10 μm contained in a medical powder. In addition to an active substance, a powder contains also a substance being a carrier, e.g., lactose.
Structural solutions of inhalers adapted to administer medicinal inhalation agents using a medicinal substance in the form of a dry powder have been known for many years.
For example, the U.S. Pat. No. 3,991,761 published in 1976 discloses an inhaler for administering powdered medicinal products contained in a capsule. The inhaler comprises a body portion having a chamber for placing therein a capsule, piercing devices in the body portion, capable of perforating a capsule in the capsule chamber, and air intake passages communicating with the capsule chamber and arranged in such a manner that air drawn through these passages, when inhaling air through an inhaler passage, leading from the chamber imparts a rotary and shaking motion to a capsule in the capsule chamber. The inhaler is substantially comprised of two main parts, a body portion of the inhaler and a tubular or mouthpiece portion. These two portions are rotatably joined and releasably latched to each other to allow access to the interior of the body portion so as to place a capsule containing the substance for inhalation in a position in the capsule chamber. Following perforation of the capsule by the piercing devices, inhalation by the patient through the tubular or mouthpiece portion causes the powder to be drawn out of the capsule and entrained in the inhaled air.
The air intakes are arranged so that intake air passes tangentially into the capsule chamber, and the capsule chamber has an elongated recess in the bottom wall thereof, in which recess the capsule in the chamber rests when the inhaler is not in use. The air intake is drawn from the recess into the capsule chamber by the air passing through the capsule chamber from the intake passages to the inhalation passage upon inhalation. The body portion and tubular portion are preferably pivotally attached together by means of a pivot pin, the axis of which is parallel to the axis of the tubular portion by which is placed on one side thereof, allowing disengagement or locking by a simple movement of one portion with respect to the other about an axis parallel to the axis of the tubular portion of the inhaler. The piercing devices comprise movable push-buttons, each having a set of elongated spikes arranged to enter a capsule in the recess within the capsule chamber and to effect perforation thereof by pressing a push button. In the preferred embodiment, there are two such push-buttons, each being maintained in a normal position by four independent springs, each being held in place by rims on the body which engage cooperating shoulders on each push button. Each of the push buttons has four elongated metal spikes. Perforation of a capsule in the elongated recess at the bottom of the capsule spinning chamber is thus simply effected by a simple pressing one or both of the push buttons.
The shape of the elongated recess in the bottom wall of the capsule is preferably substantially the same as that of a conventional medication capsule, the recess being generally rectangular with rounded ends. Preferably the spikes or pins of the piercing devices are coaxial with the recess so that a capsule is perforated at its ends. The capsule chamber is preferably circular so that a pierced capsule is caused to rotate solely by the tangential intake air upon inhalation. The intake air also acts to draw the capsule out of the recess upon inhalation so that operation is effectively automatic. The diameter of the capsule chamber is slightly larger than the length of a conventional medication capsule so that there is a small clearance between the chamber and the ends of the capsule as it rotates; causing shaking of the capsule as it strikes against the cylindrical wall of the capsule chamber, thereby urging the powder out from the capsule and causing it to be mixed with the intake air upon inhalation.
The tubular portion of the inhaler consists essentially of a circular pipe having at one end a base having an abutment stop for placing in the inhaler body. The base of the tubular portion forms, when the parts of the inhaler are assembled together, the upper part of the capsule chamber and has a slightly concave surface for facilitating the rotation of a capsule. At the opening of the inhalation passage of the tubular portion there is a grating, suitably dimensioned to optimize the air/powdered substance ratio.
The Polish patent application No. P.412009 discloses a single-dose dry powder inhaler. The essence of this technical solution is use for perforating a capsule of two assemblies of three spikes of 0.8±0.1 mm in diameter, having slanted edges, arranged to form an equilateral triangle. The spikes in the particular assemblies are turned 180° degrees relative to each other. This way, there is provided generation of an aerosol of solid particles in the air, having a fraction of a suitable particle size distribution.
The document No. WO 2005/113042 discloses an inhaler comprising a hinge enabling an articulated mounting the mouthpiece portion to the back edge of the body. This allows to move the mouthpiece portion between an open position for inserting a capsule and a closed position for dosing, about an axis perpendicular to the longitudinal axis of the inhaler, by a user applying a pushing force to the mouthpiece portion. The inhaler body comprises a pair of opposite axial grooves with the hinge axles placed therein, protruding out of the hinge element of the mouthpiece portion.
Examples of similar technical solutions are disclosed in the patent specification Nos. GB1122284, EP0005585, EP1603615, EP2865403 and EP2617451. A common feature of the structure of these inhalers is that they each comprise a first chamber in which a capsule containing an active substance is placed, elements for perforating the capsule and air intake passages, a second, usually oval chamber, in which, upon inhalation by a user, a perforated capsule rotates to release a medicine from the capsule through said perforation, and a mouthpiece with a grating, constituting an air outlet and, upon inhalation, a passage for transporting the medication released from a perforated capsule in the oval chamber.
The solution constituting the subject of the invention is also based on the size of the particles of a medication. Nevertheless, other structural solutions are proposed, which, on one hand, ensure appropriate distribution, so-called “de-aggregation” of a medication into particles smaller than 10 μm, and on the other hand provide universality of the solution, whereby adaptation of the structural parameters allows to use the device with different kinds of medications. The air passage system with adapted structural parameters enables administration of different kinds of active substances.
This objective is attained by means of a single-dose dry powder inhaler, as defined in independent claim 1. Preferable embodiments of said inhaler are defined in claims dependent thereupon.
Another purpose of the invention is to provide a universal technical solution based on the above-described principle, which will be operable within a broad range of self-resistance coefficient, while ensuring delivery of any medication of the required particle diameter distribution, wherein the amount of fraction particles smaller than 10 μm is bigger.
This objective is attained by means of a single dose-dry powder inhaler, as defined in independent claim 4, whereas the preferred embodiments thereof are defined in claims dependent thereupon.
Yet another objective is to provide a method for adjusting a universal inhaler and a method for dosing a specific medication with particle sizes falling within the required scope and with the required self-resistance coefficient of the device.
This objective is attained by means of a method for adjusting a single-dose dry powder inhaler, as defined in independent claim 10, whereas the preferred embodiments thereof are defined in claims dependent thereupon.
The invention will now be described in more detail with reference to the figures of the drawing, wherein:
The technical solution according to the invention is also based on the size of the particles of an active substance, however, different structural solutions are proposed, which, on the one hand, ensure a suitable breaking, so-called “de-aggregation” of a medicine into particles having diameter less than 10 μm and, on the other hand, provide a universality of the solution such that adapting the design parameters allows for the device to be used with different kinds of medicines. The air passage system with adapted design parameters enables administration of different kinds of active substances.
Detachment of particles of a medicinal substance from the carrier is effected as a result of a collision of still homogeneous particles of the medicine-carrier aggregates with other particles: i) in the capsule itself by means of generation of negative pressure upon a patient's inspiration, which increases also in the capsule itself as a result of perforating the cover of the capsule; ii) with the walls of the chamber which the capsule with a medicine enters under the pressure upon leaving the basic chamber, wherein, as a result of rotation, a centrifugal force breaks down the particles released from the capsule; iii) with the poles of the mesh that separate the space in which the capsule with a medicine rotates, and the outlet tube in the mouthpiece of the device; iv) with the walls of the tube forming an outlet passage for the inhaled air; v) with the walls of the constriction in the tube forming an outlet passage for the inhaled air.
The first parameter of the device characteristics is its self-resistance coefficient RD (hPa0.5 min/dm3) used to classify inhalation devices as low- (RD<0.07 hPa0.5 min/dm3), medium- (RD ranging from 0.07 to 0.1 hPa0.5 min/dm3) and high-resistance (RD>0.1 hPa0.5 min/dm3) devices.
The proposed solution in the form of an air passage system having adapted structural parameters allows to adapt the device to a patient's possibilities and needs, as a result of which, it is possible for the device to fall within the low-, medium- or high-resistance range.
Another parameter significant for an inhalation device is the above-mentioned aerosol particle size distribution.
The essence of the invention is the shape and the cross-section area of the air intake passages, structural elements of a modular mouthpiece with an internal constriction, a capsule rotation chamber and a grating with structural parameters in a single-dose dry powder inhaler, adapted for different kinds of a dry powder containing a medicine, in particular, particular components of the modular mouthpiece 21 are interconnected by means of a latching system ensuring durability of the connections. The structural supporting element of the entire system is the body 1, in which the supporting elements are 4 pillars 2 tipped with latches 3 providing a permanent connection with the upper cover 15 by means of a system of special latch spots 18 in the cover 15. The body 1, by means of a special system of ribs 5, is a carrier for a transparent capsule chamber 11. It comprises a capsule chamber 14, in which a capsule is perforated by means of spikes 10 movable in guide holes 13, allowing a powder to be released from the capsule coating during the inhalation process.
Another important feature of the invention is the air passage system in the modular mouthpiece 21. The structural solutions based on the possibility to use different widths of the intake passages 25 and different internal diameter S1 of the tube 21C by means of the internal constrictions 27, which decrease the through diameter S2, allow to adapt the device to the needs of a specific user, whom can be recommended a specific therapy applying this method.
The solution described herein is based on a system of two opposite push-buttons 7 fitted in the device, comprising: lower 9 and upper 8 protrusions, matching the system of lower guides 16 in the body 1 and upper guides 19 in the cover 15, as well as springs 23 allowing depression of the push-buttons 7 following introduction of a spike 10 through a guide hole 13 in the transparent capsule chamber 11 into the capsule chamber 14. The inhaler ensures precise perforation of a capsule, increasing the effectiveness of the therapy and the possibility to use the device multiple times.
The inhaler according to the invention ensures high efficiency of operation of the air passage system by means of tight connections between the particular elements and the entire structure, as well as by means of the precision of the preparatory processes carried out inside the inhaler prior to the proper inhalation stage, such as perforating a capsule.
Precise perforation of a capsule coating by means of specially shaped spikes movable through the guide holes allows proper administration of a therapy and ensures an efficient process of braking the participles into suitable fractions.
It is due to the nature of an ailment or the possibility to inhale harder, that the producers apply different structural solutions that satisfy particular needs. Unfortunately, these solutions are capable of handling only one medication, which, for example, in the case of application of a low-resistance device, does not yield suitable results. Therefore, the practice shows that inhalation devices are selected to match a specific medication. If a patient has to take several different medicines of different effectiveness, a manufacturer produces separate devices for each medicine. The modularity of the described device and its adjustable parameters allow using a single device falling within the medium- and high-resistance range for different treatment types. This opinion is based on an analysis of RD values of the structural solutions matrix (Table 1) relative to the RD values available on the market of commercial inhalers of different resistivity (Table 2).
From a patient's point of view, in the process of designing the structure, one needs to take into account the so-called scope of a patient's cooperation with an inhaler, as shown in
In the process of designing an air passage system having adjustable structural parameters, it was taken into account that in the case of high-resistance inhalers, it is rarely possible or not possible at all for an ill patient to inhale with a force generating a flow of 100 L/min. The comparative data set (Table 2) contains information about the maximum flow values necessary to arrive at a suitable therapeutic effect.
1Dysk
2Turbuhaler
3Dysk
4Turbuhaler
5Easyhaler
5Handihaler*
Owing to its modularity and application of different structural elements, the described solution allows selecting a suitable treatment and a medication having suitable parameters, which, on one hand, by means of suitable structural solutions, will be subjected to “de-aggregation,” that is, detachment from the carrier particles, and, on the other hand, will be broken down into smaller fractions of a medication.
A “de-aggregation” process takes place already in a capsule following its perforation by means of the spikes 10 in the capsule chamber 14 in the glass 11. Holding the mouthpiece 21C in their mouth while inhaling, a patient sucks in the air which flows into the inhaler through a system of at least two air intake passages 25, which, in the described solution, are characterized by having a fixed height “H” and being capable of adjusting a suitable width “W” parameter. Application of a suitable ratio of the height parameter to the width has an influence on the characteristics of self-resistance of the device, as shown by the data (Table 1). The air flowing in through the passages 25 generates negative pressure which extracts a capsule from the capsule chamber 14 situated in the glass 11. The capsule enters the rotation chamber 26 in the mouthpiece base 21B, wherein it collides rotatingly with the chamber walls, as a result of which, the powder released from the capsule smashes against the chamber walls and the other particles rotating in the chamber. Subsequently, the aerosol being formed flows into the mouthpiece tube 21C through the mesh 21A located in the mouthpiece base 21B, separating the space of the rotation chamber 26 from the mouthpiece tube 21C, wherein the particles are further broken down by the poles of the mesh 21A. As a result of the rotational motion, the particles floating within the circular diameter of the tube channel are subjected to further fractioning by colliding with each other, and, when passing through the internal constriction 27, they are broken down further as a result of increased speed of the aerosol and their increased rotation following passing through the internal constriction 27. The results of the measurements in Table 1—a significant change in the RD values is possible in the case of a significant narrowing of the channel in the mouthpiece tube 21C. The final effect of the inhalation process is a release of an aerosol containing a medication through the mouthpiece tube 21C, through the mouth and into the upper airways and, depending on the content of fractions smaller than 10 μm, to the furthermost parts of the lower airways.
A comparison of the emitted aerosol particle size distribution in the few selected inhaler modules presented herein with the original Fantasmino inhaler (the dispersion was applied to Flutixon, measurements were performed using the diffraction method in a Spraytec spectrometer). Qstd airflows were applied corresponding (with the accuracy of ±5%) to the standard pressure decrease 4 kPA in each of the tested inhaler modules.
The results obtained for the D1 modules—38% (
In other words, with regard to this, what is described above, a single-dose dry powder inhaler is shown generally in
The inhaler according to the invention comprises a chamber element 11. The chamber element 11 comprises a substantially flat deck on one side of which there is a capsule chamber 14 in communication with an opening running through the deck of the chamber element 11 such as to allow access to the chamber 14 in order to place therein a capsule containing a medication. Furthermore, the chamber element 11 comprises side walls protruding from the deck of the chamber element 11 and surrounding the capsule chamber 14, as shown in
The inhaler according to the present invention comprises an upper cover 15 for closing the body 1 of the inhaler. The upper cover 15 comprises, substantially in its centre, a capsule chamber 14 access opening, as shown in
The inhaler according to the present invention comprises push-buttons 7 for perforating a capsule in the capsule chamber 14. As shown in
Thus, as described above, the body 1, the chamber element 11, the upper cover 15 and the push-button 7 form together the body assembly. The inhaler body assembly according to the present invention provides a chamber 14 for placing therein a capsule containing a medication, in which chamber 14 the capsule is perforated during the operation of the inhaler. Furthermore, the inhaler body assembly comprises push-buttons 7 with spikes 10, thus providing means for perforating a capsule containing a medication.
The inhaler according to the present invention comprises a mouthpiece base 21B. The mouthpiece base 21B comprises a rotation chamber 26 with an opening running to the tube 21C. As shown in
The inhaler according to the invention comprises a mouthpiece mesh 21A. The mouthpiece mesh 21A comprises poles on which a medication is de-aggregated, as described above. In addition, the mouthpiece mesh 21A prevents too large particles of a not de-aggregated medication and capsule coating particles from entering a patient's airways. The mouthpiece mesh 21A is arranged in the opening of the rotation chamber 26 of the mouthpiece base 21B, as shown in
The inhaler according to the invention comprises a mouthpiece tube 21C. The tube 21C constitutes a pipe element one end of which is configured to be placed in a patient's mouth for inhaling a medication from an inhaler according to the invention. The other side of the tube 21C comprises latches for coupling with the mesh 21A. Inside the tube 21C there is a tube constriction 27, which decreases the through diameter of the tube 21C for increasing the de-aggregation of a medication by an inhaler according to the invention. The size of the through diameter of the mouthpiece tube 21C is adjustable by means of the constriction 27 depending on the needs, thus regulating the clearance of the tube. The size of the constriction 27 of the mouthpiece tube 21C can be freely adjusted such that the percentage of coverage of the internal passage of the mouthpiece tube 21C is the range of 0%-100%. The percentage of coverage of the passage of the mouthpiece tube 21C is practically adjustable within a range of 0%-95%. As already mentioned, the percentage of coverage of the passage of the mouthpiece tube 21C is adjustable within a range of 0%-85%. For the percentage of coverage equaling 0%, the constriction 27 of the passage of the mouthpiece tube 21C equals zero. In other words, for the clearance of the passage of the mouthpiece tube 21C equaling 0% of coverage, the internal passage of the mouthpiece tube 21C does not contain a constriction. By changing the size of the constriction 27 of the tube 21C and, consequently, the percentage of coverage of the internal passage of the mouthpiece tube 21C, it is possible to adjust de-aggregation of a medication, thus allowing adapting an inhaler according to the present invention to the needs of a patient undergoing a treatment involving at least one medication. As already described above, by providing a mouthpiece tube 21C having a specific constriction 27, an inhaler is provided providing particles of an active substance of a medication smaller than 10 μm for a specific medication, and by providing a plurality of mouthpiece tubes 21C having a specific internal diameter, an inhaler according to the present invention can be adjusted for specific medications ensuring de-aggregation of particles of an active substance of a medication smaller than 10 μm. The mouthpiece tube 21C comprises latches 29 for joining with the mesh 21A. As shown in
The mesh 21A is placed in the opening of the rotation chamber 26 of the mouthpiece base 21B, with which mesh 21A the mouthpiece tube 21C is joined by means of the tube latches 29 and the mesh latch sites to create the mouthpiece 21 of the inhaler of the present invention.
Thus, as described above, the mouthpiece base 21B, the mouthpiece mesh 21A and the mouthpiece tube 21C form together the mouthpiece assembly. The mouthpiece assembly of the inhaler according to the invention provides intake passages 25 for supplying air into the inhaler, a rotation chamber 25 for releasing a medication from a capsule, de-aggregating it and forming an aerosol with the air supplied through the intake passages 25, as well as the tube 21B for further de-aggregation of an aerosolized medication and for its inhaling by a patient through the mouthpiece 21.
The mouthpiece assembly described above is a modular mouthpiece. This means that a series of mouthpiece bases 21B is produced, having different geometries of air intake passages 25, constituting a generic array with increasingly smaller inside measurement of the air intake passages 25, as described above. In other words, a series of mouthpiece bases 21B are produced, having equal ratios of the width “W” of the air intake passages 25 to their height “H” with an increasingly smaller inside measurement of the air intake passages 25. The particular mouthpiece bases 21B in an array constitute modules of the mouthpiece base. Separately, a series of tubes 21C are produced, having different constriction 27 sizes, constituting a generic array with increasingly smaller through diameters. Particular mouthpiece tubes 21C in an array constitute modules of the mouthpiece tube. To adjust the working parameters of the inhaler according to the invention to a specific medication, a suitable mouthpiece base module and a suitable mouthpiece tube module are selected and assembled together as described above, to arrive at a suitable mouthpiece assembly to be fitted in the inhaler, as described above.
In another embodiment of the invention, the mouthpiece base 21B, the mouthpiece mesh 21A and the mouthpiece tube 21C, forming together the mouthpiece assembly, are mutually integrated. In such case, a plurality of generic arrays for different selected geometries of the air intake passages 25 are produced. This means that a generic array of mouthpieces 21 are produced, wherein the inside measurement of the air intake passages 25 in the mouthpiece base 21C is fixed, and the size of the constriction 27 of the mouthpiece tube 21C changes in the array. Next, another generic array is produced, where the inside measurement of the air intake passages 25 in the mouthpiece base 21C is fixed but has a value different from that in the previous array, while in the current array the constriction 27 of the mouthpiece tube 21C changes. Such arrays of the mouthpieces 21 are produced for all required inside measurements of intake passages 25 of different sizes of constriction 27 of the mouthpiece tube 21C. In other words, series of mouthpieces 21 are produced in generic arrays for the required values of the ratios of the widths “W” of the air intake passages 25 to their heights “H” and for the required sizes of the constriction 27 in the mouthpiece tube 21C. In such a case, in order to adjust the working parameters of the inhaler according to the invention to a specific medication, a suitable mouthpiece 21 is selected as an integrated module and mounted in the inhaler as a mouthpiece assembly, as described above.
The body assembly is removably hinge-connected to the mouthpiece assembly such that the mouthpiece assembly can be tilted away from the body assembly from a closed position to an open position. The hinge groove 16 of the upper cover 16 is latched on the hinge grip 24 of the mouthpiece base 21B to form a fastening connection, a hinge connection, allowing the mouthpiece base 21C to tilt away rotatingly relative to the upper cover 15, as shown in
The inhaler of the invention comprises a cover 22 placed over the mouthpiece tube 21C and a mouthpiece base 21, as shown in
Now, general operation of the inhaler according to the invention will be described, whereby its operation is the same for any geometry of the air intake passages 25 in the mouthpiece base 21B and/or the constriction 27 in the mouthpiece tube 21C. The cover 22, if being in place, is removed from the inhaler and is opened as described above, if closed. Next, a capsule containing a medication is placed in the capsule chamber 14, and the inhaler according to the invention is closed, as described above. The push-buttons 7 are pressed resulting in the spikes 10 of the corresponding push-button 7 moving in the guide holes 13 to perforate the capsule containing a medication in the capsule chamber 14. After releasing the pressure exerted on the push-buttons 7, the springs 23 cause them to return to their initial position and cause the spikes 10 to retreat from the capsule chamber 14. Next, air is sucked in through the free end of the mouthpiece tube 21C such that negative pressure is generated in the inhaler causing air to be sucked into the inhaler through the air intake passages 25 in the mouthpiece base 21B. Air is inhaled by a patient through the mouthpiece 21 to inhale a medication from a capsule or by a testing device for testing the properties of the inhaler according to the invention. The negative pressure generated in the inhaler according to the invention causes a perforated capsule to be entrained from the capsule chamber 15 of the chamber element 11 to the rotation chamber 26 of the mouthpiece base 21B. Simultaneously, the air sucked into the inhaler according to the invention by the air intake passages 25 of the mouthpiece base is caused to rotate intensively in the rotation chamber 26. The intensive rotation of air causes the capsule to collide rotatingly against the walls of the rotation chamber 26 to release therefrom a medication and to cause its de-aggregation as a result of the particles of the medication colliding against each other, against the capsule remains and against the rotation chamber walls 26 in the rotating stream of air, resulting in a decrease in the size of the particles of the medication. This causes the formation of an aerosol of particles of the medication suspended in the air sucked into the inhaler through the air intake passages 26. Next, the aerosol passes into the mouthpiece tube 21C through the mouthpiece mesh 21A, wherein its poles cause potential further de-aggregation of the medication in aerosol and, consequently, a reduction in the size of the particles of the medication. While passing through the mouthpiece tube 21C with the constriction 27, the aerosol is subjected therein to a strong flow disturbance. As a result of said disturbance, the particles of the medication collide multiple times against each other and against the walls inside the tube 21C, in particular, against the constriction 27 in the way of the flow, if any, causing an even bigger de-aggregation of the particles of the medication, hence the size of its particles suspended in the air. After passing through the constriction 27, the aerosol of the medication leaves the mouthpiece tube 21C of the inhaler according to the invention. As a patient inhales air through the inhaler, the aerosol of the medication enters the patient's airways. In the case when air is inhaled through the inhaler by a testing device, the aerosol inhaled through the tube 21C is subjected to testing to determine the characteristics of the inhaler with the pre-set geometries of the components of the inhaler according to the invention and to determine the distribution of the particle size of the medication tested. Next, the inhaler of the invention is open, as described above, and the inhalation residues, if any, are removed from the capsule chamber 14 and the rotation chamber 26. The inhaler is then ready for another inhalation, as descried above. If the inhaler is no longer to be used, it is closed, as described above, and the cover 22 is placed on the mouthpiece assembly.
The Inventors have tested the inhaler according to the invention to determine self-resistance of the inhaler while providing an aerosol with active substance particles smaller than 10 μm.
The tests of the inhaler according to the invention in the first series for the first version models are described in detail above. These models were made of resin by means of 3D printing. To summarize the above detailed description, a series of modules 1, 2, 3 of mouthpiece bases 21C is provided having a ratio of the width “W” to the height “H” of 1:0.85, 1:0.50 and 1:0.25, respectively, and a series of A, B, C, D mouthpiece tubes 21B having the sizes of the constriction 27 resulting in an internal diameter of 0% of coverage (no constriction), 33% of coverage, 66% of coverage and 85% of coverage, respectively, as shown in Table 1 above. The inhaler has been tested in terms of the RD coefficient values for the particular modules for all combinations of the base modules 21 B and the tube modules 21C, and the results are shown in Table 1 above. Subsequently, as described above, selected combinations of the mouthpiece base 21B and the mouthpiece tube 21C were tested for de-aggregation of the medication tested. The test results for particular combinations of the mouthpiece base 21B and the mouthpiece tube 21C of the inhaler according to the invention are presented in the graphs of
The Inventors have tested the inhaler of the invention also in the second series for the first and the second version for different combinations of the geometries of the components of the inhaler according to the invention in terms of its self-resistance. The test models in the second version were made of resin using a 3D printer, wherein one of them was made of ABS using injection technology.
The inhalers of the invention have been tested using the measurement system shown in
The tests were carried out using integrated inhaler mouthpieces 21 having the geometries specified in Tables 3 and 4 below for particular versions. The data shown in Table 3 constitutes source data for the first-version inhalers, based on which the data shown in Table 1 above was prepared.
The inhaler of the invention was tested in terms of integrated mouthpieces 21 in the geometrical variants, as presented in T 5 below, wherein the geometrical features of the mouthpiece 21 are shown by means of the codes from Tables 3 and 4 above for the first and the second version of the inhaler, respectively.
Inhalers comprising mouthpiece 21 variants have been tested by means of the above-described measurement system to determine self-resistance of the inhaler for the particular variants of the mouthpiece 21 in the second version. The aggregate results of the measurements for particular variants of the first and second versions are presented in Table 6 below.
1Kruger P., Ehrlein B., Zier M., Greguletz R. (2014). Inspiratory flow resistance of marketed dry powder inhalers (DPI). Eur Respir J 44 Suppl 58, 4635.
2Sosnowski T.R., Gradoń L. 2004. Badanie oporów aerodynamicznych inhalatorów proszkowych. Inż. Chem. Proces. 25, 1619-1625.
3Hejduk A., Urbańska A., Osiński A., Łukaszewicz P., Domański M., Sosnowski T.R. (2018). Technical challenges in obtaining an optimized powder/DPI combination for inhalation delivery of a bi-component generic drug. J. Drug Deliv. Sci. Technol. 44, 406-414.
4Sosnowski T.R. (2017). Own research.
The test results of an inhaler according to the invention comprising mouthpiece 21 variants show that it is operable within the entire range of self-resistance of inhalers. In other words, as explained above, such geometrical parameters of an inhaler according to the invention can be selected as to allow it to operate within a scope ranging from a low-resistance to a high-resistance inhaler. The test results, however, indicate that low and medium self-resistance of the inhaler are the easiest to achieve. This range offers the biggest selection of the methods of attaining this objective by narrowing down the air intake passages 25 in the mouthpiece base 21B and/or by decreasing the internal diameter of the mouthpiece tube 21C. A local constriction 27 of the mouthpiece tube 21C, however, contributes to a better de-aggregation of the particles emitted by the inhaler and, consequently, to arrive at a bigger amount of fractions smaller than 10 μm entering a patient's mouth.
The Inventors have also analyzed the influence of the size of the openings of the mouthpiece mesh 21A on the self-resistance coefficient of the inhaler according to the invention, wherein the geometries of the components of the mouthpiece 21 were as presented in Table 8.
As described above, the test results in the first series confirm that the proposed inhaler according to the invention, having variable geometry of the mouthpiece 21 is characterized by a wide range of internal resistance allowing to generate the resistance of typical commercial dry-powder inhalers. Increased internal resistance can be generated by providing air intake passages 25 of a mouthpiece base 21B having a decreased cross-section and a mouthpiece tube 21C having a big constriction 27.
Thus, the present invention discloses a universal single-dose dry powder inhaler, which, depending on the geometry of the components of the mouthpiece 21 can be used within a broad range of the self-resistance coefficient, also referred to herein as specific resistance, internal resistance, resistivity or simply resistance of the inhaler, from high-resistance inhalers to medium-resistance inhalers to low-resistance inhalers. Furthermore, regardless of the internal resistance of a given inhaler, it ensures de-aggregation of particles of a medication, wherein amount of a medication particles smaller than 10 μm is suitable.
Therefore, the present invention provides a single-dose dry powder inhaler, which can be adjusted for application with any medication. Thus, there is no need to produce a plurality of inhalers each dedicated for a different medication. Moreover, providing replaceable modules of a mouthpiece assembly having different geometries or an integrated mouthpiece assembly having different geometries allows to use a single inhaler for inhaling different medications without having to have a plurality of dedicated inhalers.
As described above in detail, a dry-powder inhaler is operable within an entire useful range of resistivity of known dry-powder inhalers. Below a method for selecting a mouthpiece assembly for an inhaler according to the invention will be described for a reference medication.
A reference medication is here understood to mean a medication having a specific composition, for which, based on models, a certain particle size distribution has been determined, in particular, for active substance particles, wherein said distribution will potentially be most beneficial therapeutically, that is, the so-called originator, or a medication having a specific composition and a specific particle distribution, in particular, active substance particle distribution, wherein said particle distribution has been tested for therapeutic properties and has been granted a marketing authorization.
In the first stage, a mouthpiece assembly is selected, either integrated or mouthpiece modules, as described above, comprising air intake passages 25 of the mouthpiece base 21B and a mouthpiece tube 21C having specific geometry, characterized by a specific self-resistance coefficient RD and which will later constitute a reference inhaler in the process of selecting a suitable inhaler. Such a reference inhaler is subjected to tests to determine particle size distribution of a medication in an aerosol of said medication, generated using a reference inhaler and, if necessary, deposition of particular fractions of the medication in a patient's airways.
In the second stage, the test results are compared against the data for a reference medication to determine if the obtained particle size values are correct relative to the reference medication. If the test results for the reference inhaler are incorrect, one determines if the particle size values obtained for the reference inhaler are bigger or smaller than those for the reference medication.
In such a case, in the third stage, a different mouthpiece assembly is selected, comprising air intake passages 25 and a mouthpiece tube 21C having different, specific geometries. If the particles of an aerosolized medication are bigger than those for the reference medication, then a mouthpiece assembly is selected comprising air intake passages 25 of the mouthpiece base 21B and a mouthpiece tube 21C such that the self-resistance coefficient RD1 of the next inhaler is greater than self-resistance RD of the reference inhaler. If the particles of an aerosolized medication were smaller than those for the reference medication, then a mouthpiece assembly is selected comprising air intake passages 25 of the mouthpiece base 25 and a mouthpiece tube 21C such that the self-resistance coefficient RD1 of the next inhaler is smaller than self-resistance RD of the reference inhaler. The above-described method for selecting the next inhaler is shown illustratively in
Where between a reference inhaler and another inhaler having a lower or higher self-resistance coefficient RD1 there is a possibility to select a mouthpiece assembly having geometrical parameters, which, theoretically, can yield particle size distribution results similar to those of the reference medication and ensure a better deposition of particular fractions in a patient's airways, then tests should be carried out for the inhaler comprising a mouthpiece assembly having such parameters. If the test results are similar to those of the reference medication, it should be concluded that such an inhaler with the mouthpiece assembly having given geometrical parameters of the air intake passages 25 of the mouthpiece base and the mouthpiece tube 21C is the inhaler with the target mouthpiece assembly that will be dedicated for a specific formulation.
As described above, the method of the invention thus allows to adjust an inhaler for a medication allowing to obtain an aerosol of the medication having a desired particle distribution, in particular, active substance particle distribution, preferably smaller than 10 μm. Use of the inhaler according to the invention eliminates the need to provide a plurality of separate inhalers dedicated for specific medications that need to be administered in the form of an aerosol containing particles characterized by a specific particle size distribution of a medication, especially of an active substance.
The inhaler of the invention is described herein for inhaling a medication in the form of a capsule. However, the inhaler of the invention may be used for inhaling a medication in the form of a portion placed in the capsule chamber 14. In such a case, the inhaler does not comprise the push-buttons for perforating a capsule.
The term “medication” as used herein is understood to mean a pharmaceutical composition, also referred to as a medicine, containing at least one active substance and additional and auxiliary substances suitable for the composition for inhaling in the form of a dry powder, especially a carrier. The present invention does not relate directly to a medication, hence the issue of a medicinal composition used in the inhaler of the invention will not be discussed herein in detail.
The features indicated in the above-described embodiments of the invention, especially the preferred ones, can be combined or replaced in any given way and in any given combination, whereby all new connections or combinations possible are deemed to be fully disclosed in the description of the present invention, provided that they do not contain mutually conflicting features.
The invention was described above by means of preferred embodiments by way of example only. Based on the above disclosure a specialist in the field will recognize that modifications, variants or equivalents are possible that fall within the spirit and the inventive intention of the present invention without exceeding the scope of the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| P-422716 | Aug 2017 | PL | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2018/056672 | 8/31/2018 | WO | 00 |
