The invention relates to a medical apparatus and method, and in particular to an inhaler for delivering a powdered medicament to a user, and a method for delivering such a powdered medicament.

Many powdered medicaments or medicines are supplied in pharmaceutical capsules. Such capsules are typically made of gelatine, and contain and protect the medicament. The medicament is typically in the form of an active pharmaceutical ingredient (API) packaged in the capsule together with an inert carrier powder, such as a lactose powder. An API powder is typically of particle size 2 to 5 micrometers, and constitutes between 1 and 5 wt% of the contents of a capsule. The carrier powder is typically of much larger particle size. A lactose carrier powder is typically of particle size 70 to 100

micrometers.

Many pharmaceutical capsules of this type are designed for use with a capsule dry powder inhaler (cDPI), for entraining the powder contents of a capsule into an air stream or air flow for inhalation by a patient or user.

Conventional inhalers of this type commonly suffer from numerous

disadvantages leading to problems such as failure to extract all of the powder from a capsule, and failure effectively to aerosolise the API in the inhaled air flow. The target for most inhaled APIs is absorption in the lungs, and inadequate detachment of the API from the carrier fraction disadvantageously leads to deposition on, for example, the throat of a user rather than the API being carried with the inhaled air flow into the lungs.

Summary of the Invention

The invention provides an inhaler and a method for delivering a powder as defined in the appended independent claims to which reference should now be made. Preferred or advantageous features of the invention are set out in dependent subclaims. In a preferred embodiment, the invention may thus provide an inhaler, such as a cDPI, for use with a pharmaceutical capsule containing an API and a carrier powder. Such an inhaler may thus be operable with a pharmaceutical contained in a capsule but may not, for example, be suitable for use with a pharmaceutical contained in a blister or provided in other forms. The inhaler may comprise a pharmaceutical capsule opener for opening the capsule for extraction of the capsule contents. The inhaler may comprise an inhaler inlet, preferably open to the atmosphere to allow air to be drawn into the inhaler. The inlet is upstream of a capsule chamber for, in use, retaining at least a part of an opened pharmaceutical capsule. The inhaler may comprise one or more capsule chambers. If only one is present, then the opened capsule is advantageously retained in, or opening into, the chamber. If more than one capsule chamber is present, then each may retain a part of the opened capsule. A typical capsule may be separated into two capsule portions, by sliding the capsule portions apart. Both capsule portions may be retained in one capsule chamber or, preferably, each capsule portion may be retained in a respective one of two capsule chambers. Advantageously, the (or each) capsule chamber operates, while a user inhales through the inhaler, to allow extraction of the API and the carrier powder from the opened capsule. The inhaler advantageously further comprises a deagglomeration chamber downstream of the capsule chamber for, during inhalation, acting to deagglomerate at least a portion of the API from the carrier particles, such as more than 10%, or 20%, or 30% or more of the API. Thus, API and carrier particles and agglomerates of the two particle types extracted from the opened capsule in the capsule chamber are entrained in a flow of air leading to the deagglomeration chamber. At this point, much of the API is attached to, or tends to adhere to, particles of the carrier fraction. Within the deagglomeration chamber, the flow of air is advantageously deflected or made turbulent so as mechanically to deagglomerate or detach or separate the API from the carrier powder. For example, accelerating the powder in a turbulent air flow or by impact against walls of the deagglomeration chamber

advantageously encourages the API to detach from the carrier powder. The relatively small size of the API powder then causes the detached API to be more effectively aerosolised, or entrained, into the air flow. Such a

deagglomeration chamber may advantageously be in the form of a swirl chamber, or through-flow or axial-flow cyclone chamber, preferably in the form of a converging axial-flow cyclone.

When the inhaler is used, a patient or user inhales air through the inhaler, from the inhaler inlet through the capsule chamber and the deagglomeration chamber, and out through an inhaler outlet downstream of the

deagglomeration chamber. The inhaler outlet may comprise or be coupled to a mouthpiece.

In a preferred embodiment of the invention, when a quantity of inspiratory energy (or power) is applied by a user drawing air through the inhaler, the inhaler is designed such that a first portion of the available energy (or power) is used, or acts, in the capsule chamber to extract the powder from the capsule, and a second portion of the available energy (or power) is used, or acts, in the deagglomeration chamber to encourage detachment of the API from the carrier powder and aerosolisation of the API for inhalation. Advantageously, as much as possible of the available inspiratory energy (or power) is used, in total, in the capsule chamber and in the deagglomeration chamber, and as little as possible is used, or absorbed, in other portions of the inhaler.

The efficiency of an inhaler can be expressed in terms of the percentage of the API contained in the capsule which is effectively separated from the carrier powder and aerosolised for delivery to a user's lungs. In a conventional inhaler, efficiencies of 15% to 20% may commonly be achievable, because approximately 15% to 20% of a typical API readily separates from, or falls off, the carrier powder. To increase the efficiency of an inhaler to levels above 15% to 20% is more difficult.

In the inhaler of the preferred embodiment described above, it is therefore preferred that the second portion of the inspiratory energy, which is used or absorbed in the deagglomeration chamber for separating the API from the carrier powder, is at least one third of the total inspiratory energy.

Advantageously, the second portion of the energy may be greater than 0.5, 0.6, 0.7 or even 0.75 of the total inspiratory energy, in order to increase the overall efficiency of the inhaler.

A sufficient portion of the inspiratory energy may be used or absorbed in the capsule chamber (or chambers) to extract the powder from the capsule. It is preferred that this first portion is more than 5%, 10%, 15%, 20% or 25% and/or less than 20%, 25%, 30% or 35% of the available energy.

Any portion of the available energy not used, or absorbed, in portions of the inhaler other than the capsule chamber and the deagglomeration chamber is preferably minimised, for example being less than 5% or 10% or 15% of the available energy. This may be achieved by minimising changes in pressure or momentum of the airflow in any portion of the inhaler other than in the capsule chamber and in the deagglomeration chamber.

In order to maximise the available energy used, in total, to remove the powder from the capsule and to deagglomerate the API from the carrier powder, the inhaler preferably comprises one or more air inlets leading to the capsule chamber or chambers, and directs all air passing through the capsule chamber(s) to the deagglomeration chamber before delivery to the patient using the inhaler. In other words, the capsule chamber(s) and the

deagglomeration chamber are preferably connected in series, with no air inlets leading to the deagglomeration chamber without first having passed through a capsule chamber and/or with no air passages bypassing the capsule chamber(s) or the deagglomeration chamber. If more than one capsule chamber is present they may be connected in series or, preferably, in parallel. The structure of the chambers within the inhaler is designed so as to achieve the desired energy split between the chambers, automatically on inhalation.

By contrast, in conventional cDPI devices, the inspiratory energy is used almost entirely to extract the powder from the capsule rather than in another portion of the inhaler (a separate chamber) to detach the API from the carrier powder.

The energy absorbed in each portion of the inhaler is proportional to the air pressure drop across that portion of the inhaler.

Thus, the portion of the inspiratory energy used in the deagglomeration chamber may be expressed as follows. When inspiratory energy is applied by a user drawing air through the inhaler inlet, the capsule chamber, the deagglomeration chamber and the inhaler outlet, the user generates an inlet pressure (P,) at the inhaler inlet, an outlet pressure (P ₀ ) at the inhaler outlet, and an intermediate pressure (P _int ) between the capsule chamber and the deagglomeration chamber. If more than a third of the energy is absorbed in the deagglomeration chamber, then (Pin _t -Po)/(PrPo) ^> 0.33. Similarly, if more than 5% of the energy is absorbed in the capsule chamber, then (Pi-Pint)/

Referring to P _int as a single value involves an assumption that any pressure drop between the capsule chamber outlet and the deagglomeration chamber inlet is negligible. As any energy absorbed in any channel or passage between the capsule chamber and the deagglomeration chamber is to be minimised by the inhaler design, as described above, and as the pressures in the inhaler may vary to some extent during inhalation, this is a reasonable assumption. If any energy absorbed in any such channel passage link were to be assessed in more detail, then a pressure at an exit from the capsule chamber and a pressure at an entrance to the deagglomeration chamber would have to be considered.

It is desirable to open the pharmaceutical capsule after insertion of the capsule into the inhaler, so that the contents of the opened capsule are initially contained within the inhaler. Thus, the inhaler preferably comprises a capsule opener, or capsule opening means or apparatus. This may comprise a means for piercing or cutting the capsule. However, a conventional pharmaceutical capsule comprises two portions, or halves, slidingly engaged with each other, and the capsule opener advantageously operates by separating the capsule portions or capsule halves. Thus, in a preferred embodiment, the inhaler comprises two portions which are slidable or movable relative to one another, each inhaler portion gripping one end of the capsule so as to separate the two capsule portions. Alternatively, the capsule portions may be separated by bending the capsule.

After a capsule is opened, the opened capsule is retained within the capsule chamber. Alternatively, an inhaler may comprise two capsule chambers, each capsule portion of an opened capsule preferably being retained in a respective capsule chamber. The opened capsule may be held in a fixed position within the or each capsule chamber but is preferably free to move within the or each capsule chamber. Air flow through the capsule chamber or chambers then removes the powder contents from the capsule. In a preferred embodiment, an air inlet opens tangentially into the or each capsule chamber so as to set up a rotating flow of air within the capsule chamber, for example causing an opened capsule to tumble or spin so that the contents fall out.

The or each capsule chamber is then linked or coupled by an air channel to a deagglomeration chamber. The inhaler may comprise one or more

deagglomeration chambers, each linked to one or more capsule chambers. In a preferred embodiment, the deagglomeration chamber may be cylindrical or frusto-conical, with the or each air channel entering the deagglomeration chamber tangentially, or at a suitable angle to set up a helical air flow about an axis of the deagglomeration chamber. This may lead to rapidly accelerating air flow and help to impact the API and carrier powder against walls of the deagglomeration chamber, to detach the API from the carrier powder.

Alternatively, the deagglomeration chamber may comprise baffles against which the powder may impact. Advantageously, any change in the momentum of the air flow leaving the or each capsule chamber, for example tangentially if the capsule chamber contains a rotating flow of air, is minimised in directing the air flow into the deagglomeration chamber, so as to minimise any pressure drop between an exit from the capsule chamber and an entry to the deagglomeration chamber.

If the air flow within the deagglomeration chamber is helical or rotary, then vanes or fins may be provided at an air outlet from the inhaler or from the deagglomeration chamber to reduce rotation of the air flow as it exits the inhaler and before inhalation.

Preferably the inhaler, as configured for inhalation, comprises no moving parts. Preferably the inhaler comprises no mechanical valves for redirecting or changing air flow during inhalation.

In a preferred embodiment, the inhaler presents a relatively high resistance to air flow during inhalation, in order to generate high air flow speeds within the inhaler and advantageously long inhalation times. In the US Pharmacopeia standard test, an inhaler embodying the invention may advantageously have a Qout value (air flow rate at the inhaler outlet at a pressure drop of 4 kPA across the inhaler) of less than 50, 40, 30, 25 or 20 litres per minute. This may be achieved by selection of the dimensions and internal structure of the inhaler as the skilled person would appreciate, using the directions in this patent application.

Specific Embodiments and Detailed Description of the Invention

Specific embodiments of the invention will now be described by way of example, with reference to the accompanying drawings, in which;

Figure 1 is a three-quarter view of an inhaler according to a first embodiment of the invention, ready for inhalation; Figure 2 is a three-quarter view of the inhaler of Figure 1 in an open position for loading with a pharmaceutical capsule;

Figure 3 is a three-quarter view of the inhaler of Figures 1 and 2, illustrating the air flow within the inhaler, during use;

Figure 4 is a three-quarter view of the inhaler of Figures 1 to 3, in a condition after opening a pharmaceutical capsule; Figure 5 shows plan, side and end views of the inhaler of Figures 1 to 4, in a closed condition ready for inhalation;

Figure 6 shows plan, side and end views of the inhaler of Figures 1 to 5 in an open condition;

Figure 7 shows an inhaler according to a second embodiment, in an open condition ready for loading a pharmaceutical capsule; and

Figure 8 shows a plan view of the inhaler of Figure 7, in an open condition.

Figures 1 to 6 illustrate an inhaler 2 according to a first embodiment of the invention. The inhaler comprises two identical mouldings, or inhaler portions, 4, 6 coupled at a hinge 8. The two mouldings are openable by pivoting at the hinge, and can be latched together, in a closed condition, by snap-fit hooks 10. The hinge and the hooks also permit lateral sliding of one moulding relative to the other, in the closed condition, to the position illustrated in Figure 4. This permits opening of a pharmaceutical capsule as described below.

When the mouldings are clipped together, in the closed condition illustrated in Figures 1 and 5, the inhaler portions define, between themselves, two generally-cylindrical capsule chambers 12, 14, a deagglomeration chamber 16, and two air channels 18, 20 linking respective capsule chambers to the deagglomeration chamber. Air inlets 24, 26 of the inhaler lead from the external atmosphere tangentially into each capsule chamber. The air channels leave each capsule chamber tangentially, encouraging air flow in the same rotational direction within each capsule chamber as the tangential entrance of the air inlets. A central vane 22 is positioned within each air channel, to prevent the capsule or a capsule portion from leaving the capsule chamber while minimising resistance to air flow in the air channels. The air channels enter the deagglomeration chamber tangentially, and at an angle to the deagglomeration-chamber axis, so as to set up a helical flow of air about the axis of the deagglomeration chamber. Changes in the air flow momentum in the channels are therefore minimised, reducing energy losses and pressure changes in the channels. At an outlet end of the inhaler, the deagglomeration chamber terminates at a mouthpiece 28. The mouthpiece contains longitudinal fins or vanes 30 to reduce the rotation of the air flow before inhalation.

To use the inhaler, a user or patient opens the two inhaler portions or mouldings 4, 6, by releasing the snap-fit hooks 10 and pivoting about the hinge 8. Within each moulding, at a wall portion separating the capsule chambers, an open-ended slot 32, 34 is provided into which a pharmaceutical capsule 36 may be urged. A conventional capsule is in the form of two blind-ended, cylindrical capsule portions, each moulded with a hemispherical closure at one end. During manufacture, the capsule is formed by sliding the open ends of two such capsule portions together, one inside the other. The widths of the slots are smaller than the diameter of the capsule, so that a central cylindrical portion of the capsule is gripped, or pinched, by both slots when the inhaler mouldings are closed together. Lateral sliding of the inhaler mouldings relative to one another, to the position illustrated in Figure 4, pulls the two capsule halves, or capsule portions, apart. At the full extent of the lateral sliding travel of the inhaler mouldings the opposing slotted wall portions have travelled away from each other far enough (each slotted wall portion carrying one of the capsule portions) so that the capsule portions become fully disengaged from each other. The inhaler mouldings are then slid back to the position shown in Figure 1. A small offset of the opposing slots allows the opposing wall portions to push the capsule portions free of the slots as the wall portions return towards each other, depositing one capsule portion 46, 48 in each capsule chamber. To achieve this, the slots may be laterally offset from each other, or angularly offset so as to twist or rotate the capsule portions slightly as the capsule portions separate.

A user then inhales through the mouthpiece, creating an air flow through the inhaler as illustrated by the arrows in Figure 3. Air from the atmosphere is drawn through the air inlets into the capsule chambers. Each capsule chamber contains half of the opened capsule, which is encouraged to tumble and rotate by the air flow 40 circulating within each capsule chamber. This removes the powder contents from each capsule portion and entrains the contents into the air stream. Air from the capsule chambers is then drawn off tangentially through the air channels into the deagglomeration chamber. Drawing the capsule chamber air tangentially serves to conserve momentum and set up the subsequent double-helical flow efficiently - i.e. it minimises aerodynamic losses between the first and second stages. The offset, tangential entry of the air channels into the deagglomeration chamber sets up a rapid helical air flow within the deagglomeration chamber, causing the API and carrier particles to impact side walls of the deagglomeration chamber, encouraging detachment of the API from the carrier particles. The double-helical flow is designed to maximise swirl within the deagglomeration chamber by effectively interweaving the two "solid ribbons" of airflow. The rotation of the helical air flow is reduced as the air, containing aerosolised API, flows past the vanes in the mouthpiece, into the mouth and lungs of the user.

As shown in the drawings, for convenient packaging, the air flow in the two capsule chambers rotates about capsule chamber axes which are parallel to each other and perpendicular to a lateral plane of the inhaler, and the air flow in the deagglomeration chamber rotates about an axis perpendicular to the capsule chamber axes. Figures 7 and 8 illustrate a second embodiment of the invention. This inhaler 60 is of similar construction to the inhaler of Figures 1 to 6 except that it has only one capsule chamber 62. An air channel 64 links the capsule chamber to a deagglomeration chamber 66. A second (optional) air channel 68 links an air inlet 70 of the inhaler to the deagglomeration chamber, to provide two tangential air channels entering the deagglomeration chamber, to promote helical flow. Figure 8 shows a plan view of the opened inhaler 60.

The inhaler as described above, in its various embodiments, advantageously separates the processes of emptying powder from a pharmaceutical capsule, and detaching an API from a carrier powder. In addition, however, embodiments of the invention may advantageously be constructed so that the limited amount of inspiratory energy provided by a user inhaling through the inhaler is deployed as effectively as possible to produce API entrained, or aerosolised, in the air drawn through the air outlet. Thus, the sizes of the air inlet or inlets, the sizes and shapes of the capsule chamber or chambers, the lengths and cross sections of the air channel or channels, and the dimensions and construction of the deagglomeration chamber may all be selected or predetermined so as to divide the available inspiratory energy between the capsule chamber(s) and deagglomeration chamber(s), while simultaneously providing a desired, predetermined level of resistance to the flow of air through the inhaler, to optimise the rate at which air is inhaled by the user. For example, increasing the size of the deagglomeration chamber may tend to reduce the pressure drop within the deagglomeration chamber, and thus reduce the proportion of the energy available for detaching the API from the carrier powder. Alternatively, increasing the dimensions of the capsule chamber or chambers may decrease air flow velocity within those chambers and reduce the energy available for emptying the powder from the capsule portions.