SINGLE DOSE DRY POWDER INHALER DEVICE
Field of the Invention
The present invention relates to a single dose dry powder inhaler device that
delivers dry powder medication contained in a capsule to the lungs of a patient, wherein
the capsule gets dissected by the blades along its entire length thereby providing improved
lung deposition of the medication.
Background of the Invention
The administration of medicaments by inhalation is well known. There are several
inhaler devices available for delivering medication to the patients. Presently, the most
widely used systems for inhalation therapy are: a) pressurized metered dose inhalers
(MDIs) & b) dry powder inhalers (DPIs).
Pressurized metered dose inhalers (MDIs) use a propellant to expel droplets
containing the pharmaceutical product to the respiratory tract. However, despite their
practicality and popularity, MDIs have some disadvantages:
i) droplets leaving the actuator orifice could be large or have an extremely high
velocity resulting in extensive oropharyngeal deposition reducing the amount
of medicament which penetrates into the lungs;
ii) the amount of medicament which penetrates the bronchial tree may be further
reduced by poor inhalation technique i.e. due to the common difficulty of the
patient to synchronise actuation from the device with inspiration;
iii) chlorofluorocarbons (CFCs), such as freons commonly used as propellants in
MDIs are disadvantageous on environmental grounds as they have a proven
damaging effect on the atmospheric ozone layer. Nowadays, potentially more
environmentally friendly hydrofluoroalkanes (HFA) are being used as
substitute of CFCs in MDIs. Even they cannot be considered completely
devoid of environmental impact.
iv) HFA inhalers require special maintenance and cleaning. Before use, they must
be primed with several sprays, and some require priming every few weeks or
so.
Dry powder inhalers (DPIs) constitute a viable alternative to MDIs for the
administration of medicaments to airways. The main advantages of DPIs are:
i) being breath- actuated delivery systems, they do not require co-ordination of
actuation, since the release of the medicament is dependent on the patient's
own inhalation;
ii) they do not contain propellants acting as environmental hazards;
iii) the velocity of the delivered particles is the same or lower than that of the flow
of inspired air making them more prone to follow the air flow rather than the
faster moving MDI particles, thereby reducing upper respiratory tract
deposition.
DPIs can be divided into two basic types: i) single dose dry powder inhalers, for
the administration of pre-subdivided single doses of the active compound in single dose
compartments, like capsules or blister packs; ii) multidose dry powder inhalers (MDPIs),
either with pre-subdivided single doses or pre-loaded with quantities of active ingredient
sufficient for multiple doses; each dose is created by a metering unit within the inhaler.
When only a single dose is desired, multiple dose dry powder inhalers are typically
too bulky, costly, inefficient, or difficult to use. Several single dose inhalers intended for
one-time use have been proposed. However, they have not achieved widespread use.
Disadvantages remain with single dose inhalers relating to powder storage, dose
uniformity, dispersion performance, ease of use, cost, and other factors. Accordingly, there
is a need for an improved inhaler for efficiently providing a single dose of a powdered
medicament.
Single dose dry powder inhaler devices using capsule are previously known in the
art.
U.S. Patent No. 4,013,075 teaches a device, comprising a detachably connected
mouthpiece and body, for powdered substances contained in a capsule which is
longitudinally inserted into the cylindrical bore of a pivotably mounted carrier member for
pivoting into a transversely disposed recess in the body of the device. A pair of cutting
blades is attached to the body of the device at opposite ends of the recess for severing the
ends of the capsule during the pivoting movement. A bore in the mouthpiece and body
coincides with the bore of the carrier member and with holes in the blades so that air can
be drawn longitudinally through the severed capsule for inhalation or insufflation.
U.S. Publication No. 2007/0295332 discloses an inhaler device for powdered
medicaments. The device has a body that has a recess for holding a capsule containing a
powdered medicament to be inhaled, at least one air passage that is tangentially disposed
to the recess, and a mouthpiece that includes a coaxially disposed inhalation passage that
communicates with the recess of the body. The body has a pair of opposed spring based
push-buttons that each include at least one piercing element for piercing the capsule when
loaded in the recess. The medicament is released from the pierced capsule when air is
drawn through the air passage(s) into the recess and swirled about therein. The mouthpiece
is pivotally attached to the edge of the body so that it is pivotable between an open loading
position and a closed dispensing position about an axis that is perpendicular to the
longitudinal axis of the inhaler.
The single dose capsule using dry powder inhaler devices known in the prior art
either have a low resistance to airflow, as a result of which the powder tends to be
administered too quickly and a considerable quantity of the powder impinges in the mouth
and throat, where it serves no beneficial therapeutic effect. On the other hand many known
dry powder inhaler devices have a greater resistance to airflow. In both cases, sufficient
quantity of the powder does not reach the lungs. Indeed, the chief objective of the device
from a therapeutic aspect is the maximization of the quantity of powder that reaches the
lungs. This objective is defeated with both of the devices of the prior art. A further
disadvantage of some known dry powder inhaler devices is their mechanical complexity,
resulting in an increased production cost and difficult assembly.
Unlike in the prior art devices, the capsule in the present invention is neither
pierced to release the content with difficulty (greater resistance to air flow), nor made to
rotate, vibrate or twist open (means to decrease resistance to air flow after piercing). Nor
are the capsule contents released by cutting off both the ends of the capsule (low resistance
to air flow). Here, the only movement present is that of the powder within the capsule that
is dissected along its entire length that provides better lung deposition of the powder.
Accordingly, it is an objective of the present invention to provide an improved
single dose dry powder inhaler for constantly delivering a measured dose amount of the
dry powder medication into the lungs of a patient resulting in better lung deposition. The
inhaler device is small, compact, and easy to operate.
Summary of the Invention
According to one embodiment, there is provided a single dose dry powder inhaler
device with improved lung deposition, the inhaler device comprising:
- a sliding mouthpiece;
- a capsule chamber;
- at least one blade which is inserted into slots in the capsule chamber;
- an outer body covering the capsule chamber, and;
- a lower cover with an air inlet hole;
wherein the capsule chamber has a recess for the insertion of a capsule, and said capsule
gets dissected by the blades along its entire length.
According to another embodiment, there is provided a single dose dry powder
inhaler device with improved lung deposition, the inhaler device comprising:
- a removable cover cap with a clip;
- a sliding mouthpiece;
- a capsule chamber;
- two blades which are inserted into slots present at two sides of the capsule
chamber;
- an outer body with a window covering the capsule chamber, and;
- a lower cover with an air inlet hole;
wherein the capsule chamber has a recess for the insertion of a capsule, and said capsule
gets dissected by the blades along its entire length.
Brief Description of the Drawings
The single dose dry powder inhaler which constitutes the present invention is
shown in the accompanying drawings of the preferred embodiment in which:
Figure 1 is a top perspective view of the inhaler.
Figure 2 is a cross-sectional perspective view of the inhaler.
Figure 3 is a bottom and rear perspective view of the inhaler.
Figure 4 is a front perspective view from one side of the inhaler.
Figure 5 is a break-up perspective view of the different elements of the inhaler.
Figure 6 is a detailed perspective view of Figure 5.
Detailed Description of the Invention
Referring to the drawings, the single dose dry powder inhaler device of the present
invention shown in Fig. 4 is intended to deliver a single dose of a powdered medicament
stored in a capsule to the patient through inhalation. The device illustrated in Fig. 5 & 6
comprises a removable cover cap (a) with a clip (a-i), a sliding mouthpiece (b) intended to
deliver medication into the lungs, the capsule chamber (c) for housing the capsule, an
outer body (d) with a window (d-i) covering the chamber and a lower cover (e) for
removal of unused medication and capsule shell from the device. The lower cover (e)
contains an air inlet hole (e-i) through which air is drawn into the capsule chamber during
inhalation.
The removable cover cap (a) has an inbuilt clip (a-i) with a thumb impression. The
cap snugly fits into the mouthpiece (b) so as to prevent the device from foreign matter
such as dirt, dust, etc. entering into it and thereby contaminating the medication.
The sliding mouthpiece (b) has an opening containing a mesh (b-i) on the outside,
through which the patient inhales the medication. This portion of the device on the inner
side has an inbuilt provision for a plunger, which basically aids in capsule insertion. A
screw (b-ii) enables the mouthpiece to slide vertically upwards & downwards. When
slided upwards, the mouthpiece reveals open the capsule chamber.
Inside the device is a capsule chamber (c) which has slots (c-i) for holding the
blades (c-ii) in their position. The chamber has a recess (c-iii) for housing the capsule
while it is to be inserted for getting dissected by the blades (c-ii).
The outer body (d) covers the capsule chamber (c) and contains a window (d-i)
which is placed symmetrically in line with the chamber. This enables the patient to view
the capsule contents and also its fate from outside of the device.
Finally, the chamber (c) opens to a lower cover (e) containing an air inlet hole (e-i)
at the bottom. The lower cover (e) prevents the medication from falling out of the device
after it is dissected. Due to its hinge facility, the lower cover (e) cannot be separated from
the device; hence can be opened and closed based on the need to dispense the used
medication.
To use, the user removes the cover cap (a) to expose the mouthpiece (b). The
mouthpiece (b) is allowed to slide vertically upwards and the capsule containing the
medication is placed on the mouth of the capsule chamber (c). The mouthpiece (b) with
the inbuilt plunger is then allowed to slide vertically downwards, resulting in the
dissection of the capsule against the blades (c-ii) along the entire length of the capsule
body. The dissected capsule thus falls into the chamber (c) and in turn is supported by the
lower cover (e). During inhalation, air flows in from the air inlet hole (e-i) at the bottom of
the lower cover (e) thus creating turbulence inside the chamber (c). As a result, the powder
inside the capsule shell is dissipated in the device and flows out through the mesh (b-i) of
the mouthpiece (b) and finally into the oropharyngeal cavity and into the lungs.
The inhaler device of the present invention can be made of any suitable material,
for example tough plastic materials such as acrylonitrile-butadiene-styrene (ABS), methylmethacrylate-
acrylonitrile-butadiene-styrene (MABS) or an anti-static material. If desired,
the material is substantially transparent to help the user to more readily see and understand
how the device works. This encourages users to use the device in the correct way and
continue to use the device in that manner for the full term of their treatment leading to
increased patient compliance.
The capsule for use in the inhaler device of the present invention contains a single
dose of a powdered medicament. The powdered medicament may be suitable for the
treatment of respiratory tract diseases, for example - bronchodilators such as salbutamol,
salmeterol, formoterol, or pharmaceutically acceptable salts thereof; antimuscarinic agents
such as ipratropium, oxitropium, tiotropium, glycopyrrolate, or pharmaceutically
acceptable salts thereof; anti-inflammatory drugs including steroids such as budesonide,
beclamethasone, fluticasone, ciclesonide, mometasone or pharmaceutically acceptable
salts thereof.
'Improved lung deposition' as used herein refers to 20-30% of the total dose of the
powdered medicament reaching the lungs of the patient. Determination of lung deposition
of the active ingredients from the dry powder inhaler device is done using an in-vitro
method, i.e., Twin stage impinger (TSI). The TSI is a two-stage separation device used in
the assessment of oral inhalation devices. Stage one of the apparatus including the upper
impinger is a simulation of the upper respiratory tract. Stage two which includes the lower
impinger is a simulation of the lower respiratory tract. A suitable liquid is used in both the
upper and lower impinger.
The inhaler is placed in the mouth of the TSI. Air is caused to flow through the
apparatus by means of a pump, which is connected to stage two of the TSI. Air is sucked
through the apparatus from the mouth, which flows through upper tubing via the upper
impinger and the lower tubing to the lower impinger where it bubbles through the liquid
and exits the apparatus via outlet pipe. The liquid in the upper impinger traps any particles
with a size such that it is unable to reach stage two of the TSI. Fine particles (particles able
to penetrate to the lungs in the respiratory tract), are able to pass into stage two of the TSI
where they flow into the lower impinger liquid.
The percentage of the active material in each stage of the TSI is calculated from
the standard response for each test and the mean for the tests is calculated to give an
indication of the proportion of the active particles reaching the second stage of the TSI
apparatus. The respirable fraction (fine particle fraction) is calculated as the percentage of
the total amount of drug emitted from the inhaler device that reaches stage two of the TSI.
This value gives an indication of the proportion of active particles which would reach the
deep lung in a patient.
The unique features of the dry powder inhaler device of the present invention are:
1. Simple and easy to use (can be easily used by patients of the age group
between 5 yrs - 70yrs).
2. Portability due to its compact shape.
3. Multi-compartments with synchronized built-in features.
4. Better lung deposition of the medicament into the lungs (e.g. 20-30% of the
total dose of medicament)
The invention is further illustrated by the following non-limiting examples.
Example 1
Determination of lung deposition of the active ingredients from the dry powder
inhaler device
Twin stage impinger was used to assess the efficiency of the delivery of the active
particles to the lungs by the inhaler device of the present invention. 30 ml of a mixture of a
solution of decane sulphonic acid sodium salt (pH 2.5) and acetonitrile (70:30) was put
into the lower impinger and 7ml of a mixture of a solution of decane sulphonic acid
sodium salt (pH 2.5) and acetonitrile (70:30) was put into the upper impinger. The pump
was adjusted to give an air flow rate of 30 litres per minute and 60 litres per minute in the
apparatus, for two different sets of readings.
The device was filled with ten capsules and turned to inhalation position. The
mouthpiece end of the device was located and the pump of the apparatus was switched on
for 4 seconds. The assembled inhaler was removed from the mouthpiece and the discharge
sequence was repeated for further nine times (nine capsules). The apparatus was
dismantled after discharging the length delivery.
The sections of the apparatus making up stage one of the TSI were washed into a
flask and made up to 100 ml with a mixture of a solution of decane sulphonic acid sodium
salt (pH 2.5) and acetonitrile (70:30). The sections making up the second stage of the TSI
were washed into another flask and made up to 100 ml with a mixture of a solution of
decane sulphonic acid sodium salt (pH 2.5) and acetonitrile (70:30). The amount of active
substance in each section of the TSI was measured for each test.
The contents of the flasks containing the washings from the stages of the TSI were
assayed using High Performance Liquid Chromatography (HPLC) analysis (using
Hypersil ODS column with dimension of 150mm x 4.6mm x 5m) using mobile phase
[mixture of a solution of decane sulphonic acid sodium salt (pH 2.5) and
methanol (45:55)] for the content of the active material and compared against standard
solutions containing, for example, 0.5 mg ml- 1and 1 mg ml- 1of the active material.
The percentage of the active material in each stage of the TSI was calculated from
the standard response for each test and the mean for the tests was calculated to give an
indication of the proportion of the active particles reaching the second stage of the TSI
apparatus. The values of deposition of emitted dose by TSI using the inhaler device of the
invention for Avessa 100 Octacaps are detailed in Table 1. Each capsule contains
Formoterol Fumarate Dihydrate IP equivalent to Formoterol Fumarate 6 meg and
Fluticasone Propionate IP 100 meg.
Table I : Lung Deposition Data for Inhaler of the Invention
Example 2
The method detailed above was used to determine lung deposition data of
marketed dry powder inhaler devices (DPI), namely Turbospin from PH&T, Cyclohaler
from PCH (4 pins) and Monodose from Plastiape (4 pins) at a pump air flow rate of 30
litres per minute and a comparison was made with the values obtained for the inhaler
device of the present invention. Avessa 100 Octacaps were used as the test capsule dosag
form in the devices. The comparative results are presented in Table 2.
Table 2: Comparison Between Lung Deposition Values of Marketed DPI Devices to
the Device of the Invention
Fine Particle
Fraction
Product Capsule Shells Parameter
DPI Devices Tested Results at
Evaluated Used Evaluated
30 1/min
23 - Turbospin from PH&T 26 %
Deposition of Cyclohaler from PCH (4
Avessa HPMC based
emitted dose pins) 19 - 2 1 %
100 Size 3 Capsules
Octacaps from Capsugel at different Monodose from Plastiape
flow rates (4 pins)
Device of the present 24 - 27 %
invention
We claim:
1. A single dose dry powder inhaler device with improved lung deposition, the
inhaler device comprising:
- a sliding mouthpiece,
- a capsule chamber,
- at least one blade which is inserted into slots in the capsule chamber,
- an outer body covering the capsule chamber, and;
- a lower cover with an air inlet hole;
wherein the capsule chamber has a recess for the insertion of a capsule, and said
capsule gets dissected by the blades along its entire length.
2. The single dose dry powder inhaler device of claim 1, wherein the inhaler device
further comprises a removable cover cap with a clip.
3. The single dose dry powder inhaler device of claim 2, wherein the said cap snugly
fits into the mouthpiece to prevent contamination of the medicament by entry of
foreign matter.
4. The single dose dry powder inhaler device of claim 1, wherein the sliding
mouthpiece has an opening containing a mesh through which the patient inhales
the medicament.
5. The single dose dry powder inhaler device of claim 1, wherein the said device
contains two blades.
6. The single dose dry powder inhaler device of claim 1, wherein the capsule
comprises a medicament.
7. The single dose dry powder inhaler device of claim 6, wherein the medicament to
be dispensed using the device may be selected from those suitable for the treatment
of respiratory tract diseases including bronchodilators such as salbutamol,
salmeterol, formoterol, or pharmaceutically acceptable salts thereof; antimuscarinic
agents such as ipratropium, oxitropium, tiotropium, glycopyrrolate, or
pharmaceutically acceptable salts thereof; anti-inflammatory drugs include steroids
such as budesonide, beclamethasone, fluticasone, ciclesonide, mometasone or
pharmaceutically acceptable salts thereof.
8. The single dose dry powder inhaler device of claim 1, wherein said device is made
of a material selected from tough plastic materials like acrylonitrile-butadienestyrene,
methyl-methacrylate-butadiene-styrene or an anti-static material.
9. The single dose dry powder inhaler device of claim 1, wherein said device
provides lung deposition of 20-30% of the total dose of medicament into the lungs.
10. The single dose dry powder inhaler device of claim 9, wherein lung deposition is
measured using a twin stage impinger.