EP1587564A2 - Capsule pour recevoir un principe actif administrable par inhalation - Google Patents

Capsule pour recevoir un principe actif administrable par inhalation

Info

Publication number
EP1587564A2
EP1587564A2 EP03799497A EP03799497A EP1587564A2 EP 1587564 A2 EP1587564 A2 EP 1587564A2 EP 03799497 A EP03799497 A EP 03799497A EP 03799497 A EP03799497 A EP 03799497A EP 1587564 A2 EP1587564 A2 EP 1587564A2
Authority
EP
European Patent Office
Prior art keywords
capsule
medicament
chamber
longitudinal axis
medicament capsule
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP03799497A
Other languages
German (de)
English (en)
Inventor
Dieter Hochrainer
Heinrich Kladders
Burkhard Metzger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Publication of EP1587564A2 publication Critical patent/EP1587564A2/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
    • A61M15/0033—Details of the piercing or cutting means
    • A61M15/0035—Piercing means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00—Inhalators
    • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
    • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
    • A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
    • A61M15/0048—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged in a plane, e.g. on diskettes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/06—Solids
    • A61M2202/064—Powder

Definitions

  • the invention relates to a novel capsule for receiving an active ingredient that can be administered by inhalation, which is preferably intended for use in a powder inhaler operating according to the Bernoulli principle.
  • a suitable powder inhaler essentially consists of a preferably cylindrical capsule chamber, which is provided with means for opening the capsule from the side, an air inlet opening in the capsule chamber, and an air outlet opening and a mouthpiece downstream of the air outlet opening.
  • the capsule chamber is often also preferably cylindrical, being somewhat longer and somewhat wider than the capsule, so that the capsule can vibrate both axially and radially in it, but remains aligned essentially parallel to the chamber axis.
  • the terms axial and radial are synonymous with vertical (axial) and horizontal (radial) with respect to the orientation of the inhaler, in which the capsule chamber is aligned below the mouthpiece.
  • Axial also stands for an orientation parallel to the longitudinal axis of the inhaler (vertical axis), radial is the direction perpendicular to it.
  • the capsule chamber has an air inlet in the area of one of the two ends and an air outlet opening in the area of the other end.
  • the air outlet leads to a mouthpiece, being able to conduct a powder aerosol.
  • the capsule can first be opened at usually two locations on the longitudinal jacket. The openings are usually located near the two longitudinal ends of the capsule. If an air flow is now generated in the capsule chamber from the air inlet to the air outlet, it leads along the longitudinal axis of the capsule and does two things: First, the capsule is mainly moved along its longitudinal axis by the air flow.
  • the air flowing along the two capsule openings creates in front of the Capsule openings have a negative pressure in relation to the interior of the capsule, so that the powder in the capsule is entrained by the air flow and atomized in the process.
  • DE 3345722 discloses such an inhaler comprising two housing elements with a single capsule chamber that can be moved in the axial direction.
  • WO 91/02558 discloses another inhaler described at the outset, but instead of a single capsule chamber, several capsule chambers are combined in a manner similar to a revolver magazine.
  • the open sides of this magazine are delimited by walls, with the air inlet or
  • Air outlet is located.
  • This magazine is rotatably mounted in such a way that a capsule chamber is connected to the air inlet, the air outlet and the cutting elements necessary to open the capsule only in a certain position.
  • EP 0911047 discloses an inhaler with a) cup-shaped lower part which is open towards the top, b) a plate which covers the opening of the lower part and is formed perpendicular to the one capsule chamber, a button which is movable against a spring being provided on the capsule chamber , which has two ground needles for opening the capsule, c) an upper part with a mouth tube which can conduct a powder aerosol is connected to the capsule chamber and d) a lid.
  • the elements a), b), c) and d) are connected to one another by a common hinge element, so that they can be moved so that they can be folded against one another.
  • this patent application describes a capsule holder, wherein the capsule holder can be designed as a hole in the plate b) and has ribs on the edge. The capsule is clamped in this capsule holder for the purpose of storage.
  • the capsules usually used for such inhalers consist of hard gelatin, but they can also consist of a plastic material.
  • the capsules known from the prior art consist of two cup-like parts which can be telescopically inserted into one another, the capsule cap and the capsule body.
  • the outer shape of such an assembled capsule is that of a closed cylinder with hemispherical ends.
  • the cylinder has a longitudinal axis and a transverse axis.
  • the longitudinal axis is the axis that lies parallel to the generatrix of the cylinder jacket.
  • the longitudinal axis is longer than the transverse axis, so that the longitudinal section of the capsule is oval and the cross section is circular.
  • Some of the capsules have a circumferential gap at the interface between the capsule cap and the capsule body, which arises from the fact that the capsule cap always has a slightly larger outer diameter than the capsule body.
  • Another aspect of the present invention is to use such capsules in Bernoulli powder inhalers.
  • the disposable capsules according to the invention have a longitudinal and a transverse axis, the longitudinal axis being longer than the transverse axis, i.e. the length ratio of the longitudinal axis to the transverse axis, the elongation, is greater than 1.
  • the outer contour of the capsule is designed with mirror symmetry with respect to a mirror plane Sigma h dividing the longitudinal axis of the capsule. The longitudinal axis is thus perpendicular to the mirror plane. This mirror symmetry does not refer to the inner contour of the capsule. Due to the symmetrization, the inflow and vibration conditions are the same regardless of the direction in which the capsules are introduced into the inhaler. Both show the same flow behavior above the air inlet opening.
  • mirror symmetry is not understood to mean an abstract or idealized mathematical operation, but rather the transfer of this mathematical concept to what is physically and technically expedient.
  • the term “mirror symmetry” includes tolerances and blurring that occur eg result from manufacturing reasons.
  • the term “fuzzy” is understood to the extent to which an element X, which is formed on one side of the mirror plane on the capsule surface, is reproduced identically on the capsule on the opposite side of the mirror plane.
  • the smallest measurable size to which the mirror symmetry is to be applied is 0.15 mm, preferably 0.1 mm, more preferably 0.05 mm.
  • a pair of (two) protrusions should still be considered mirror-symmetrical if one protrusion has a diameter of 1 mm and the other (mirror-symmetrical) a diameter of 0.85 mm.
  • the blur in the sense of the present invention is 0.15 mm, etc.
  • the fuzzy ones include e.g. also differences of the capsules on both sides of the plane of symmetry as a result of conicity of up to 5 °, preferably up to 2 °, most preferably up to 1 °, as are usually used to detach the capsules from tools.
  • tolerance is to be understood as a location.
  • the tolerances are preferably 0 to 0.15 mm, preferably 0 to 0.1 mm, more preferably 0 to 0.05 mm.
  • a capsule is again to be used as an example of the term tolerance with a pair of (two) - in this sense - arbitrarily defined mirror-symmetrical projections. If the one projection is at longitude 0 (analogous to earth measurement), then its mirror-symmetrical counterpart on the other side of the mirror plane may be up to 0.15 mm next to it the longitude to be considered mirror symmetric, in which case the tolerance is 0.15 mm.
  • two features forming a pair of mirrors on the capsule surface can have a tolerance and blurring that deviate from the symmetry, each of 0.15 mm, preferably 0.1 mm, more preferably 0.05 mm.
  • This zone can have a width of up to 2.5 mm above and below the mirror plane, preferably up to 1.25 mm. In it you can find elements, facilities etc. that are not mirror-symmetrical counterparts or none Have a mirror-symmetrical identical counterpart on the opposite side of the mirror plane. This means that there is a zone of up to 5 mm (2.5 mm above plus 2.5 mm below the mirror plane), which is excluded from mirror symmetry.
  • the background is that in this zone, in the case of two-part capsules, the interface between the two capsule parts is preferably located, for example a weld seam, which of course cannot be produced in strictly symmetrical fashion.
  • the interface between the individual capsule elements can also be excluded from mirror symmetry in the narrowest sense with the tolerances mentioned above.
  • a possible fine structure of the interface e.g. the fine structure of a weld.
  • Such a seam should be considered approximately as a line, the height of which corresponds to the height of the weld seam.
  • Elements smaller than 0.1 mm, preferably smaller than 50 micrometers, very particularly preferably smaller than 10 micrometers, are likewise preferably excluded from the mirror symmetry.
  • the capsule consists of at least two sub-elements which are telescopically pushed into one another.
  • there are exactly two sub-elements each of these capsule parts representing a cavity with three closed and one open side.
  • the two sub-elements are connected to each other via the open sides. This opening is preferably perpendicular to the longitudinal axis.
  • the two sub-elements are a capsule body and a capsule cap.
  • the capsules are preferably of a cylinder-like shape.
  • the sub-elements can be connected to one another by suitable joining methods after the filling process. For example, gluing, banding, shrinking, friction, laser or ultrasonic welding are suitable. Alternatively or in addition to this, the sub-elements can also be connected to one another by means of clips or snap-in devices. In such an embodiment there are one or more locking means on the inner jacket of the sub-element which is pushed over one of the other sub-elements and correspondingly complementary locking means on the outer jacket of the other, complementary sub-element, which are arranged such that they lock into one another when the capsule is closed engage.
  • Such latching means can be projections and depressions which operate in a manner similar to the push-button principle, which can be punctiform and / or circumferentially annular. Arrangements are preferred in which the projections or depressions are each arranged in a ring or spiral around the jacket.
  • one or more annular projections are formed on the inner jacket of the cap and the outer jacket of the body in such a way that in the closed state of the capsule there is in each case a projection of one partial element in a recess of the other partial element.
  • these can be continuous or interrupted.
  • the projections and / or depressions are preferably designed such that they are not visible on the outside.
  • capsules consisting of two sub-elements are preferred.
  • the interface can be formed parallel to the longitudinal axis or perpendicular to it.
  • Embodiments with a seam that runs perpendicular to the longitudinal axis are preferred.
  • the seam between the sub-elements can halve the longitudinal axis or be formed at a point distant from the center.
  • the interface is preferably centered or offset from the center by 0 to 12% of the outer length, preferably from the center by 0 to 10% of the outer length, more preferably from the center by 0 to 5% the outer length offset.
  • the seam is in the middle or from offset up to a maximum of 3% of the outer length. The seam is most preferably in the mirror plane.
  • the seam can be made by any joining method, e.g. Gluing, banding, shrinking, friction, laser or ultrasonic welding can be closed.
  • the seam In embodiments in which the seam is not in the middle, it can be closed in such a way that the outer jacket is smooth at this point and the joining process does not disturb the mirror symmetry of the capsule. Otherwise the provisions on mirror symmetry and tolerances or unsharpness apply.
  • the closed capsules according to the invention can have elevations on their outer jacket. These elevations can serve as spacers when the capsule is inserted into the capsule chamber of the inhaler.
  • the height of the elevations (i.e. the distance from the base point to the apex) is preferably 0.1 mm to 5 mm, more preferably 0.5 mm to 2 mm.
  • the surveys can e.g. be designed as ribs with abrupt edges, with soft, wavy transitions or as pins. Combinations of these are also possible.
  • the tips or ridges (edges) of these elevations in the most preferred case have a minimal surface.
  • Longitudinal axis of the capsule can be arranged.
  • the term “skewed” also includes spirally arranged ribs.
  • the capsule expediently has at least three or more such ribs. It preferably has no more than nine, more preferably no more than six such ribs.
  • the length of the ribs is selected so that they guide the capsule in the capsule chamber during its axial movement without this movement being blocked.
  • the ribs preferably extend over the entire height of the capsule on its outer casing which is not curved with respect to the longitudinal axis. In this case, the ribs preferably have a triangular cross section, with a tip of the
  • the distance between two adjacent pairs of ribs is different (non-equidistant arrangement of the ribs).
  • the cross-sectional arrangement is asymmetrical.
  • a further embodiment of the capsule has an outer surface with a wave profile as just described, ribs being formed axially on this surface, ie perpendicular to the waves. These are in turn designed such that the outer edges of the ribs are equidistant from the central longitudinal axis of the capsule, the outer edges the ribs do not have a wavy surface, but an uncurved surface (parallel to the longitudinal axis).
  • pin-shaped elevations these can either be arranged linearly, possibly replacing the ribs, or their arrangement is arbitrary.
  • the pins are aligned so that the axial movement of the capsule can not be disturbed, but the capsule is guided in this movement.
  • the elevations are mirror-symmetrical on the outer surface of the capsule, the mirror plane defined above being used as a basis.
  • a preferred capsule has a macroscopically smooth outer surface, i.e. there are no surveys.
  • the term “macroscopically smooth” is understood to mean surfaces which have elevations and depressions of at most 0.5 mm, preferably up to 0.1 mm, more preferably up to 0.05 mm.
  • the cross section preferably has a round or oval shape.
  • it is a two-part, telescopically pluggable capsule made of a capsule cap and a capsule body, which, when closed, represents a cylinder with tapered ends, preferably hemispherical ends.
  • the cylinder has a longitudinal axis and a transverse axis.
  • the longitudinal axis is the axis that lies parallel to the generatrix of the cylinder jacket.
  • the longitudinal axis is longer than the transverse axis, so that the longitudinal section of the capsule has an oval geometry and the cross section has a circular geometry.
  • such a cylinder coming from the center, always has a constant external cross section until it tapers continuously in order to form the rounded ends.
  • Such a cylinder has a jacket that is not curved parallel to the longitudinal axis.
  • Such a concave shell occurs, for example, when the outer diameter of each of the two capsule parts, as viewed from the tapered end, increases steadily.
  • the outer contour of the jacket is concavely curved.
  • each of the two capsule parts coming from the tapered end, can initially run as a straight line that is parallel to the longitudinal axis before it curves slightly away from the central axis and then continue to run as a straight line, but now in one Angle alpha lies to the central axis until it finally reaches the open end of the capsule part.
  • the outer contour of the assembled capsule resembles the convex outer contour described above.
  • the capsule body - or alternatively the capsule cap - can have on the inside of its open end an edge running parallel to the inner jacket, which protrudes beyond the edge of the outer jacket and which can be inserted into the capsule cap and thereby connects the two elements (capsule cap and capsule body) , This creates a circumferential edge on the inside of the jacket, parallel to the opening, onto which the capsule cap is then attached.
  • the inner casing of this capsule part is drawn higher than the outer casing, so that at the closure point Between the capsule cap and the capsule body there is a step on which the other capsule part is seated in the closed state.
  • symmetry properties of the outer surface are assigned to the symmetry group D ⁇ h .
  • idealized means that deviations due to production technology are not taken into account and that the definitions of tolerances and blurring as defined above also apply here.
  • capsules are preferred, the outer contour of which can be ideally assigned to this symmetry group in the sense defined above.
  • the total length of the closed capsule is preferably 26.1 +0.3 mm; 23.3 ⁇ 0.3 mm; 24.2 ⁇ 0.3 mm; 21.7 ⁇ 0.3 mm; 19.4 ⁇ 0.3 mm; 18.0 ⁇ 0.3 mm; 15.9 ⁇ 0.3 mm; 14.3 ⁇ 0.3 mm; 11.1 ⁇ 0.3 mm.
  • the outer diameter of the capsule body and the capsule cap in the region of the closed capsule which is visible from the outside is preferably: 9.91 mm; 8.53 mm; 7.66 mm; 7.64 mm; 6.91 mm; 6.35 mm; 5.83 mm; 5.32 mm; 4.91 mm.
  • the dimensions of the capsule according to the invention are modeled on the commercially available capsules of the so-called size 3, as is known at least in Germany. In the telescopic capsules described, the outer diameter is preferably between 5.57 and 5.83 mm.
  • the capsules should preferably be used in powder inhalers, for example of the type described at the beginning in the prior art section.
  • the inhalers of DE 3345722, WO 91/02558 or EP 0911047 are expressly mentioned. These inhalers are about inhalers that work on the Bernoulli principle (Bernoulli inhalers).
  • These inhalers have a capsule chamber, the cross section of which is 1.1 to 2.5 times as large as the capsule diameter and whose length is 1.02 to 2 times as long as the length of the capsule.
  • the capsule chamber has at least two openings, an inlet for incoming air and an air outlet.
  • the air inlet has a smaller cross-section than the capsule chamber, so that a relatively high flow rate occurs in this area of the capsule chamber, which increases the Bernoulli effect, through which the powder in the capsule is ultimately discharged.
  • the air inlet opening is expediently arranged centrally in the bottom of the chamber.
  • a sieve plate or other device, such as projecting components, can be formed on the air outlet side, which prevents a capsule moving in the capsule chamber from slipping into the air outlet and thus blocking it, or from any capsule fragments that may have been sucked into the mouthpiece.
  • the sieve plate can, for example, be part of a funnel-shaped connecting piece which can be plugged onto the beginning of the inhalation channel leading to the mouthpiece in such a way that the funnel edge engages with the sieve plate in an insert plate which forms the bottom of the mouthpiece.
  • the sieve plate can also be exchangeably fastened in the press fit between the funnel edge of the connecting piece and a stop on the insert plate.
  • a plurality of openings can also be provided as the outlet opening.
  • the cross section available for the outflow of air from the capsule chamber is expediently larger than the air inlet opening everywhere so that the air loaded with the medicament can flow out as freely as possible.
  • the air outlet opening is expediently arranged centrally in the ceiling of the chamber, but can also be arranged laterally in the ceiling area.
  • the arrangement of the two openings is intended to guide an air flow axially through the capsule chamber.
  • the capsule chamber has at least one point along its longitudinal axis (relative to the interior of the capsule chamber) an opening for or a connection with a cutting device, which is provided with at least two pointed needles or cutting edges, around a capsule located in the capsule chamber pierce or cut open.
  • This cutting device can be displaced into the interior of the chamber against the pressure of a spring and can be operated via a spring-mounted actuation button. Since the height of the capsule chamber is determined by the length of the drug capsules, the tips or cutting edges of the cutting device are also preferably arranged in the region of the upper and lower ends of the capsule chamber.
  • the side wall of the capsule chamber can have radial bores or elongated slots facing the needles / cutting edges in the region of its upper and lower ends, which serve for the passage of the needles / cutting edges.
  • the dimension of these bores / slots is modeled on the cross-section of the needles or cutting edges.
  • the guidance of the needles of the cutting device has a sealing plate.
  • the seal between the capsule chamber in the inhalation position and the cutting device is improved.
  • the spring can be used, which causes the actuation button of the cutting device to be reset.
  • a lever system for actuating the cutting device is provided in a further embodiment.
  • This lever system is preferably confirmed from an actuation button attached to the bottom or side of the housing of the inhaler.
  • the lever system can consist of a rocker and a toggle lever, one end of the rocker acting on the actuation button and the other end of the rocker pressing one end of the toggle lever, the other end of the toggle lever attached to the cutting device advancing the cutting device.
  • the rocker and toggle lever are preferably mounted in brackets which are attached to the housing and can be pivoted about axes.
  • the capsule should be opened near its two ends for inhalation.
  • the hemispherical caps of the capsule should not be damaged. This is important because the capsule or capsule cap performs a kind of valve function.
  • the capsule Due to the pressure conditions, the capsule is drawn against the inflowing air to the inlet opening and closes it. Since the user continues to suck on the mouthpiece, a negative pressure is created in the capsule chamber, by means of which the capsule is entrained with the inflowing air in the direction of the air outlet. The negative pressure now developing at the air inlet causes the capsule to be pulled towards the inlet opening again. The whole process repeats itself in rapid succession as long as the mouthpiece is inhaling and sets the capsule in strong axial vibration.
  • the powder inhalers equipped with a capsule according to the invention which in the simplest case consist of a capsule chamber, an air inlet opening, an air outlet opening which is connected to a mouthpiece and a device for piercing the capsules, are also the subject of the present invention.
  • the air mixed with the drug in the chamber is fed as a powder aerosol through the mouthpiece to the user's mouth.
  • the mouthpiece which is generally tubular, possibly somewhat flattened, can be arranged axially or at an angle to the axis of the chamber or offset laterally to the axis of the chamber.
  • the mouthpiece of the inhaler can be designed as a cap which is placed on a lower part of the inhaler, which contains the capsule chamber. This cap can be pivoted on the edge of the inhaler housing about an axis perpendicular to the longitudinal axis of the inhaler. Mouthpiece and lower part of the inhaler housing can also be fastened to one another by a conventional plug connection. Due to the solubility or
  • Pivotal movement of the two parts is in any case substantially easier overall access, on the one hand to the capsule chamber and the cutting device in the lower housing part and on the other hand to the inner parts, such as the sieve plate, of the upper housing part (the mouthpiece-like cap).
  • the mouthpiece is flipped up in such an embodiment or the plug connection between the mouthpiece and the lower housing part is released.
  • the capsule chamber is then freely accessible so that the empty capsule can be removed and a filled one inserted.
  • the device is then closed or plugged together.
  • the inhaler according to the invention enables the drug to be dispensed more reliably with a lower standard deviation.
  • Preferred inhalers are those as initially described as embodiments of DE 3345722, WO 91/02558 or EP 0911047. At this point, the features mentioned in this section are expressly referred to again. The inhaler as described above in connection with EP 0911047 is particularly preferred.
  • inhalers have a revolver magazine with a plurality of mostly tubular chambers, each of which can be equipped with a capsule.
  • the magazine is covered on each of its two open sides by a plate, one plate containing the air inlet opening and axially the other plate containing the air outlet opening. Since the magazine is rotatably mounted within these plates, one of the chambers can be swiveled in between the two openings and thus form part of the inhalation air passage. After completing an inhalation process, the revolver magazine is rotated further until the next chamber comes into the air passage.
  • one of the two plates can be separated from the magazine to remove the used capsules Removing chambers or the entire magazine can be removed for refilling, for example.
  • the revolver magazine is detachably arranged in the inhaler housing. After the capsules in the revolver magazine have been used up, the entire revolver magazine can be replaced or refilled with capsules.
  • the inhaler housing can have an eccentrically arranged pin, onto which the revolver magazine can be attached.
  • the revolver magazine To fix the position of the revolver magazine, it can be provided with the capsule chambers, each with associated recesses for a spring-mounted locking bolt arranged in the inhaler housing.
  • the recesses are arranged so that the locking bolt only engages when one of the capsule chambers is exactly between the air inlet and outlet.
  • the resilient mounting of the locking bolt should be selected with regard to the spring constants so that accidental rotation of the revolver magazine is prevented by the locking mechanism, on the other hand the revolver magazine can be unscrewed from the locking mechanism if more force is applied.
  • Conical designs of the free end of the locking bolt and correspondingly shaped recesses have a supporting effect.
  • the locking bolt is preferably arranged coaxially to the air passage channel under the capsule chamber and has a through hole which simultaneously forms the air inlet on the bottom.
  • the locking bolt is preferably arranged centrally in the inhaler housing.
  • Locking bolt acted upon by a spring, the other end of which rests on a stopper which is detachably fastened in the inhaler housing and which likewise has a central through-hole which is part of the air passage.
  • the recesses for the engagement of the locking bolt are arranged on the bottom in the base plate of the magazine concentrically with the air inlet bores of the capsule chambers and are designed like the jacket of a flat truncated cone with the base facing outwards. These recesses are thus conical or funnel-shaped extensions of the air inlet bores, the extended region facing the locking bolt.
  • the bevels created by the expansion correspond approximately to the bevels on the head of the locking bolt.
  • these recesses have a circumferential stop edge at the base of the truncated cone shell, but still in the base plate, which serves as an anti-twist device or stop for the head of the locking bolt when it is snapped into the recess. Because of the abovementioned stop edge, the magazine cannot be rotated further when the locking bolt is engaged.
  • said stop edge takes up only part or half of the circumference of the conical recess, that is to say the funnel-shaped extension, and is arranged in such a way that it blocks the rotation of the magazine in one direction when the locking bolt is engaged, in the other But direction allows, because there the sloping wall of the funnel-shaped extension of the recess merges smoothly into the outside of the base plate.
  • only one of the recesses has a stop edge which takes up the entire circumference of the recess, so that rotation of the magazine is not possible in this recess when the locking pin is engaged. This position is then considered the end position of a magazine in which all capsules are used up. All other recesses have in this embodiment only the one-sided, i.e. one-way rotation lock, so that the magazine can only be rotated in the direction of the pivoting of a capsule chamber with an unused capsule until the previously described end position is reached, in which the Locking is complete. The user then knows that the magazine must be filled with fresh capsules when this last capsule has been used up.
  • a tongue can be attached to the locking bolt, which tongue extends as far as a stop on the inside of the operating button of the cutting device when the locking bolt assumes its upper stop position when the revolver magazine is removed. In this position, the said tongue acts as a lock for the cutting device. When the magazine is inserted, the locking bolt is pressed down again, thus eliminating the lock on the cutting device.
  • the confirmation of the cutting device can also be done with the rotary movement of the
  • Capsule magazine can be coupled, so that with a push of a button, a capsule chamber is first brought into the correct position and then immediately attacks the cutting device.
  • the revolver magazine and the part of the inhaler housing adjoining it are designed to be n-shaped, where n is a whole number indicating the number of capsule chambers, then the side surfaces of the inhaler housing part and the revolver magazine are advantageously aligned when the magazine is in the correct position , One can then determine directly from the outside whether the chamber is in the air duct defined by the air inlet and the air outlet.
  • FIG. 1 shows a closed capsule known from the prior art.
  • FIG. 2 shows an inhaler in which the capsule according to the invention can be used.
  • FIGS. 3 a to d show a powder inhaler with a revolver magazine in which the capsule according to the invention can be used.
  • FIG. 4 shows a powder inhaler with an upper part and a lower part which are movable relative to one another.
  • FIGS 6 to 13 show different embodiments of the capsule according to the Invention.
  • FIG. 1 shows a capsule (1) known from the prior art, consisting of a capsule cap (2) and a capsule body (3). It can be seen that the outer diameter of the capsule body is smaller than that of the capsule cap over wide areas. This is particularly evident in the area of the bottom, hemispherical end of the capsule body.
  • FIG. 2 shows how an inhaler can be constructed, in which a capsule chamber according to the invention is integrated.
  • a capsule chamber according to the invention In a lower part (5) with optionally two windows (6) there is a plate (7) which is connected to the capsule chamber (4).
  • the button (8) To open the capsules in the capsule chamber (4), use the button (8) with two specially ground needles, which is pressed in against the pressure of the spring (9) and thereby cuts open or pierces the capsule in two places.
  • the mouth tube (10) which is connected to the upper part (11)
  • the air gets into the lower part (5) and from there at the lower end into the capsule chamber (4).
  • the device is closed by a lid (12) which is foldably connected to the lower part (5), the plate (7) and the upper part (11), so that dust does not get into the lid when it is closed Device can penetrate.
  • blind hole-like capsule holders can be located in the plate (7).
  • a sieve plate (34) which is attached to the lower end of the mouth tube (10) or the inhalation channel leading to the opening of the mouthpiece and which covers the air outlet opening of the capsule chamber (4) when the inhaler is closed, is advantageous.
  • Optional snap hooks are not shown on the side of the mouth pipe (10) or the upper part (11) oriented towards the plate (7), which can snap into the plate (7).
  • the plate (7) has correspondingly complementary devices (depressions or holes).
  • protrusions or snap hooks can also be formed laterally so that the plate (7) can snap into the lower part (5).
  • Said devices for latching the mouthpiece (10) or the upper part (11) into the plate (7) or that of the plate (7) into the lower part (5) are such that individual elements can be easily separated again.
  • a nose can be formed such that it engages in a recess on the top of the button (8) and the button (8) so blocked so that the button (8) cannot be pressed when closed. This prevents the capsule from being accidentally punctured if the capsule is inserted prematurely.
  • FIG. 3 As can be seen from FIGS. 3a, 3b and 3c, an inhaler with revolver magazine essentially consists of an inhaler housing (5) with a mouthpiece (10) which is laterally on the upper edge of the inhaler housing (11) about an axis (13) is pivotally articulated and a revolver magazine (14) with the capsule chambers (4) for receiving the capsules.
  • the revolver magazine (14) can be plugged onto a pin (15) arranged eccentrically in the inhaler housing (5). After inserting the revolver magazine (14), the mouthpiece (10) is brought into its normal position - as a cap on the housing; the inhaler is functional. A capsule (not shown) can now be opened using the button (8).
  • the revolver magazine (14) has 6 in this case Chambers (4) for receiving the capsules, not shown.
  • the bottom of each chamber (4) has an air inlet bore (16).
  • the revolver magazine (14) also has an axial guide (17) for the pin (15).
  • the inhaler is adjacent to that under the
  • Inhalation channel (18) arranged chamber (4) the cutting device (19) which can be operated via the button (8).
  • This cutting device (19) has two needles (20) which can be introduced radially into the upper or lower part of the said chamber (4), the revolver magazine outer wall for easier passage of the needles (20) at appropriate points or openings weakened areas (21).
  • the needles (20) serve to open the capsule located in the chamber (4) near its upper or lower end.
  • the revolver magazine (14) also has conical recesses (23) below the bores (22), into which a locking bolt (24) can snap as soon as the corresponding one of the chambers (4) is coaxial with the air inlet or inhalation channel (18) of the inhaler housing ,
  • the locking bolt is also conical at its end engaging in the recess (23). At the opposite end it is acted upon by a spring (26) which is supported on a stopper (27) which is detachably fastened in the inhaler housing.
  • this plug has a central through-hole which serves as an air inlet (25).
  • one of the chambers (4) is brought into a position by rotating the revolver magazine, in which the bottom-side bore (22) or the conical recess (23) is aligned coaxially with the air inlet opening (25) .
  • the setting of the chamber (4) is facilitated by latching the locking bolt (24) into the recess (23). After the bolt has engaged, the air inlet opening (25) and the bottom opening (22) of the chamber (4) are aligned.
  • the capsule cap stands on said bottom opening (22) and closes it.
  • the cutting edges (20) are moved radially in the direction of the chamber (4), first of all the weakened areas (21) pierce or enter suitable openings in the side wall of the revolver magazine and finally open the capsule at the top and bottom near its end.
  • the tapered caps of the capsules should not be destroyed because they should have a kind of valve function.
  • the mouthpiece (10) is generally tubular, but can also be adapted to the shape of the mouth and flattened. In a modification of the embodiment shown, mouthpiece arrangements which are axial or offset at an angle to the axis of the chamber or laterally to the chamber axis are also possible.
  • the mouthpiece (10) can be provided with an essentially closed insert plate (29).
  • This insert plate (29) can also have openings.
  • the beginning of the inhalation channel (18) can be covered with a sieve, which prevents the capsule or capsule fragments from getting into the inhalation channel (18) in the mouthpiece during inhalation.
  • wall projections can be provided at the said location, which retain the capsule.
  • the sieve plate is then preferably arranged in the center of the insert plate (29), advantageously in a clamped fit between a stop (30) of the plate (29) which surrounds the air passage and the edge of a funnel-shaped connecting piece (31) which points to the beginning (32) of the inhalation channel (19) is plugged on so that the funnel edge faces the insert plate (29) and is in engagement with it.
  • the alternatively provided projections can also be arranged there.
  • the embodiment of the inhaler according to the invention shown in FIG. 4 consists of the lower part (5) and the mouthpiece (10) which are put together.
  • the bottom part contains the air inlet channel (25) which is connected to the air inlet into the capsule chamber (4).
  • the cutting device (19) is held in its normal position by a spring element (9).
  • the mouthpiece (10) contains the capsule chamber (4).
  • a sieve plate (34) prevents fragments of the capsule, for example, from being inhaled.
  • the inhaler can be axially compressed against the pressure of a spring element (35), the upper edge of the lower part reaching position (36).
  • the knives or tips (20) of the cutting device (19) can enter the capsule chamber (4) through the opening (21) and then open the capsule fixed there.
  • the lower part (5) and mouthpiece (10) are pulled apart, the capsule is inserted and the two inhaler parts are plugged together.
  • the cutting device (19) is actuated and released again. Under the pressure of the spring element (35), the inhaler returns to the starting position shown in FIG. 4.
  • the active ingredient formulation can now be inhaled from the capsule (not shown) by inhalation through the mouthpiece (10).
  • FIGS. 5 and 6 each show a mirror-symmetrical capsule (1) according to the invention comprising a capsule cap (2) and a capsule body (3).
  • the inside of the capsule body has an inward-reaching extension (37) which is inserted into the capsule cap.
  • the approximately perfectly hemispherical ends, as shown in Fig. 5, are preferred for hard gelatin capsules.
  • the injection points are somewhat recessed at the ends (FIG. 6).
  • FIGS. 7 a to d show different locking techniques with latching means on the
  • FIG. 7c has snap-type latching means, with a projection (38) on one of the capsule elements and a recess (39) for latching the projection on the other capsule element.
  • the closure variant according to FIG. 7d has a projection (40).
  • FIG. 8 shows a variant in which the side wall of the capsule cap (2), when viewed from the open to the closed end, tapers suddenly (41). The capsule body can then only be pushed into the capsule cap until it strikes the taper (41) from the inside. The position of the taper is chosen so that the mirror symmetry of the closed capsule is preserved.
  • FIG. 9 shows a variant in which the interface between capsule cap (2) and capsule body (3) is not in the mirror plane.
  • Figure 10 shows a variant with a closure according to Figure 7d.
  • FIG. 11 shows a variant with a seam running parallel to the longitudinal axis.
  • FIG. 12 shows a variant according to FIG. 11 with a closure according to FIG. 7d.
  • FIG. 13 shows a variant with a seam running perpendicular to the longitudinal axis, which is banded (41).

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pulmonology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Otolaryngology (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)

Abstract

L'invention concerne une nouvelle capsule pour la réception d'un principe actif administrable par inhalation. La capsule selon l'invention est de préférence destinée à être utilisée dans un inhalateur de poudre fonctionnant selon le principe de Bernoulli.
EP03799497A 2003-01-14 2003-12-20 Capsule pour recevoir un principe actif administrable par inhalation Ceased EP1587564A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE2003100984 DE10300984A1 (de) 2003-01-14 2003-01-14 Kapsel zur Aufnahme eines inhalativ applizierbaren Wirkstoffs
DE10300984 2003-01-14
PCT/EP2003/014694 WO2004062640A2 (fr) 2003-01-14 2003-12-20 Capsule pour recevoir un principe actif administrable par inhalation

Publications (1)

Publication Number Publication Date
EP1587564A2 true EP1587564A2 (fr) 2005-10-26

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EP03799497A Ceased EP1587564A2 (fr) 2003-01-14 2003-12-20 Capsule pour recevoir un principe actif administrable par inhalation

Country Status (6)

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EP (1) EP1587564A2 (fr)
JP (1) JP2006517421A (fr)
AU (1) AU2003300220A1 (fr)
CA (1) CA2513201C (fr)
DE (1) DE10300984A1 (fr)
WO (1) WO2004062640A2 (fr)

Families Citing this family (8)

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Publication number Priority date Publication date Assignee Title
DE102007036411A1 (de) * 2007-07-20 2009-02-12 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pulverinhalator
TR200803525A2 (tr) * 2008-05-16 2009-12-21 Bi̇lgi̇ç Mahmut Toz ilaç soluma cihazı.
JP5415341B2 (ja) * 2010-03-31 2014-02-12 株式会社吉野工業所 粉体吸入デバイス
JP6037315B2 (ja) * 2011-05-27 2016-12-07 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 吸入器及び吸入器用カプセル
PT107627B (pt) * 2014-04-29 2017-03-08 Hovione Farmaciência S A Inalador de cápsulas com dobradiça
EP3167868A1 (fr) * 2015-11-16 2017-05-17 Capsugel Belgium NV Forme posologique inviolable
EP3167867A1 (fr) * 2015-11-16 2017-05-17 Capsugel Belgium NV Forme posologique inviolable
CN111012671B (zh) * 2019-11-25 2022-07-05 上海强德食品科技有限公司 一种微胶囊的物理制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0711572A1 (fr) * 1994-05-26 1996-05-15 Unisia Jecs Corporation Dispositif d'inhalation de medicaments et sa methode d'utilisation

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Publication number Priority date Publication date Assignee Title
SE395611B (sv) * 1975-12-12 1977-08-22 Draco Ab Aerosolinhalationsanordning avsedd for inhalering genom ett inhaleringsmunstycke av farmakologiskt aktiva substanser
GB8325529D0 (en) * 1983-09-23 1983-10-26 Lilly Industries Ltd Medicinal forms
DE3345722A1 (de) * 1983-12-17 1985-06-27 Boehringer Ingelheim KG, 6507 Ingelheim Inhalator
DE3927170A1 (de) * 1989-08-17 1991-02-21 Boehringer Ingelheim Kg Inhalator
AU650953B2 (en) * 1991-03-21 1994-07-07 Novartis Ag Inhaler
DE4318455A1 (de) * 1993-06-03 1994-12-08 Boehringer Ingelheim Kg Kapselhalterung
DE19835346A1 (de) * 1998-08-05 2000-02-10 Boehringer Ingelheim Pharma Zweiteilige Kapsel zur Aufnahme von pharmazeutischen Zubereitungen für Pulverinhalatoren
GB2357488A (en) * 1999-11-17 2001-06-27 Aquasol Ltd Capsules by injection moulding

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0711572A1 (fr) * 1994-05-26 1996-05-15 Unisia Jecs Corporation Dispositif d'inhalation de medicaments et sa methode d'utilisation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2004062640A3 *

Also Published As

Publication number Publication date
AU2003300220A1 (en) 2004-08-10
WO2004062640A3 (fr) 2004-10-21
WO2004062640A2 (fr) 2004-07-29
AU2003300220A8 (en) 2004-08-10
DE10300984A1 (de) 2004-07-22
JP2006517421A (ja) 2006-07-27
CA2513201C (fr) 2012-10-02
CA2513201A1 (fr) 2004-07-29

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