Multiple-dose dispenser for dry powder inhalers

A multiple-dose dispenser for use with dry powder inhalers is disclosed. The dispenser has a two-piece construction and includes a plurality of individual, hermetically sealed chambers for retaining unit doses of a dry powder for inhalation. Also disclosed is a method for producing the multiple-dose dispenser.

FIELD OF THE INVENTION 
This invention relates generally to dry powder inhalation systems, and more 
specifically to multiple-dose dispensers for use with dry powder inhalers. 
BACKGROUND OF THE INVENTION 
Inhalation of therapeutic agents for treatment of certain respiratory 
disorders such as, e.g., bronchial asthma, is a well-known treatment 
modality. Therapeutic inhalation regimens typically involve inhalation of 
a desired therapeutic agent as a finely divided solid such as a dry powder 
or an aerosolized solution or suspension (delivered by way of a nebulizer 
or metered dose inhaler). Although numerous systems have been developed 
for inhalation with each of these dosage forms, dry powder inhalation has 
recently become more attractive as a result of certain disadvantages of 
aerosolized solutions or suspensions. 
First, metered dose inhalers typically include halogenated hydrocarbons, 
compounds that are known to be environmentally damaging. Second, metered 
dose inhalers often require adept manipulation on the part of the user to 
insure complete and accurate dosing. Careful coordination between the 
release of the aerosolized dose from the inhaler and inhalation of the 
dose by the user is required. This task often proves difficult for many 
patients and as a result, quite frequently leads to patient frustration 
and non-compliance. Third, it is extremely difficult to monitor the number 
of doses remaining in the aerosol canister. Fourth, the drug is dissolved 
or suspended in a liquid propellant, which results in the unwanted 
introduction of foreign chemical substances into the body. Each of these 
disadvantages can be avoided by the use of dry powder inhalation dosage 
forms. 
Several different types of dispensers are available for use with dry powder 
inhalation systems. These include bulk powder dispensers, single dose 
dispensers and multiple-dose dispensers. Bulk powder dispensers hold 
enough bulk powder for a plurality of doses and are typically used with an 
inhaler having a shuttle or rotary mechanism that transfers a metered dose 
from the bulk powder reserve into an inhalation chamber in the inhaler. 
Reference is made to PCT Patent WO 93/00123, published Jan. 7, 1993and to 
U.S. Pat. No. 5,239,993, issued Aug. 31, 1993 to Evans. Bulk powder 
inhalation systems have several disadvantages. For example, once the 
system has been activated to dispense the first dose, the bulk powder is 
no longer sealed from the external environment, and also, it is very 
difficult for the user to monitor the number of doses remaining in the 
bulk powder dispenser. 
An example of a single dose dispenser is provided in PCT Patent 
WO/94/06498, published Mar. 31, 1994. This patent discloses a dry powder 
inhaler system adapted to engage a single dose gelatin capsule. Although a 
single dose dispenser, such as a gelatin capsule, has the advantage of 
maintaining the integrity of the dry powder until the time of dispensing, 
this method requires a much higher level of user involvement. Each time a 
dosage is to be dispensed, the user must insert a new capsule into the 
device and then, following dispensing, remove the empty capsule shell. 
This action often requires that the device be dismantled. In an acute 
situation, such as a bronchial asthma attack, or for those with impaired 
hand movement, such as an elderly or disabled patient, this procedure can 
prove to be overly difficult and cumbersome. 
The third type of dry powder dispensers, multiple-dose dispensers, have a 
number of unit doses secured in individual chambers. An example is 
described in UK Patent Application GB 2,274,273 A, published Jul. 20, 
1994. This reference teaches a medicament pack that comprises an elongate 
base strip having a plurality of recesses spaced along its length and a 
lid sheet hermetically but peelably sealed thereto, thereby defining a 
number of cavities for inhalable dry powdered medicaments. A second 
example of a multiple-dose dispenser is disclosed in U.S. Pat. 5,388,572 
issued Feb. 14, 1995 to Mulhauser et al. This patent discloses a mesh disc 
impregnated with a series of spaced, medicament doses about the disc 
periphery. A major drawback to this dispenser is that the doses are not 
individually hermetically sealed. 
Although dry powder systems enjoy a number of theoretical advantages over 
metered dose inhaler systems, they have not reached their full potential 
due to certain shortcomings of known dry powder systems. Thus, there 
exists a need for a multiple-dose dispenser for use with dry powder 
inhalers wherein each of the individual powder chambers is individually, 
hermetically sealed. The dispenser should also include a means for 
indicating to the user how many doses remain in the dispenser, as well as 
a means for clearly indicating when all of the doses have been 
administered. The dispenser should have the capability of being 
efficiently and easily filled with accurate, small volume dry powder 
dosages. The individual hermetically sealed chambers should be sized such 
that there is sufficient head space and that the dry powder is not 
compacted within the chambers. 
SUMMARY OF THE INVENTION 
The present invention provides a multiple-dose dispenser for use with dry 
powder inhalers. The dispenser includes a plurality of individual 
hermetically sealed chambers, each retaining a unit dose of a desired dry 
powder for inhalation. Thus, the integrity of each dry powder dose is 
maintained until the seal on a particular chamber is broken. 
The multiple-dose dispenser is comprised of a first portion and a second 
portion, each having a plurality of cavities extending therethrough. One 
end (the same end) of each of the cavities in both the first portion and 
in the second portion is sealed with a conventional sealing means and one 
cavity in the second portion is so sealed on each end. The first portion 
and the second portion are bonded together, preferably by ultrasonic 
welding, wherein the open ends of the cavities in the two portions are in 
alignment, forming a number of individual hermetically sealed chambers. In 
practical realization, each of the chambers contains a unit dose of a 
desired dry powder. 
The cavity in the second portion which is sealed on each end provides a 
means to assist the user in inserting the dispenser into the proper 
dispensing position in a dry powder inhaler and to prevent inadvertent 
"double dosing" during the initial dispensing process. 
In one embodiment, the dispenser is disc-shaped and the cavities are 
circumferentially located. Preferably, the volume of each cavity in the 
second portion is equal to the volume of powder required for one dose. 
Therefore, the full volume of powder is retained in the second portion and 
the corresponding cavity in the first portion remains empty, providing 
head space and preventing compaction of the powder. Preferably, the 
chambers are cylindrically or conically shaped, allowing the dry powder to 
freely flow from a chamber when the seal is broken during the dispensing 
process. 
Another embodiment of the dispenser includes means, such as reference 
numerals or the like, for indicating to the user how many doses remain in 
the dispenser and for clearly indicating to the user that the dispenser is 
empty. Thus, the user is able to efficiently monitor replacement of the 
dispenser, thereby improving patient compliance and ensuring that doses 
will be available when needed. 
Another embodiment of the multiple dose dispenser of the present invention 
includes a drive means for functionally indexing the individual sealed 
chambers into the proper dispensing position when the dispenser is 
inserted into a dry powder inhaler. Preferably, the drive means is a set 
of ratchet teeth located on the outer periphery of the dispenser, on 
either the first or the second portion. Each of the ratchet teeth is 
spaced to correspond to one of the sealed chambers and therefore, as the 
dispenser is rotated, the next sequential dose is properly positioned for 
dispensing. As a means for unambiguously informing the user that the 
dispenser is empty, i.e., that no doses remain, a chamber adjacent to the 
cavity sealed on each end (the empty chamber) does not have a 
corresponding ratchet tooth and consequently, after this dose has been 
dispensed, the dispenser can not be rotated to the next position, that of 
the blocked cavity. 
Thus, an aspect of the present invention is a method for producing a 
multiple-dose dispenser for use with a dry powder inhaler comprising the 
steps of: 
providing a first portion and a second portion, each portion having a 
plurality of cavities extending therethrough; 
sealing one end of each cavity; 
sealing a second end of one of the cavities in the second portion; 
filling each of the open cavities in the second portion with a unit dose of 
a dry powder; 
bonding the first portion to the second portion such that the open end of 
each of the cavities in the second portion is aligned with an open end of 
a cavity in the first portion forming a plurality of sealed chambers. 
As the volume of each of the cavities in the second portion is equal to the 
volume of one dose, in another aspect of the invention, the step of 
filling each of the open cavities comprises overfilling each of the 
cavities with an excess volume of a bulk powder and removing the excess 
powder to form a level powder surface in each of the cavities. 
In yet another aspect of the invention, the step of bonding the first 
portion to the second portion comprises ultrasonic welding, wherein each 
of the sealed chambers is hermetically sealed.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Although this invention is susceptible to embodiment in many different 
forms, preferred embodiments of the invention are shown. It should be 
understood, however, that the present disclosure is to be considered as an 
exemplification of the principles of this invention and is not intended to 
limit the invention to the embodiments illustrated. 
Referring now to the drawings, FIGS. 1 and 2 depict dry powder inhaler 10 
having a multiple-dose powder dispenser disk 11 mounted therein. The 
inhaler device is described in detail in U.S. Pat. No. 5,337,740 (to 
Armstrong et al), the entire contents of which is incorporated herein by 
reference. To operate inhaler 10, cover 12, which rotates on hinge 13 when 
latch 14 is released, is opened and disk 11 is functionally inserted into 
receptacle 15 and cover 12 replaced. Mouthpiece 16 is inserted into the 
mouth of the user and movable section 17 is depressed. This action causes 
springs 18 and 19 to be compressed, which in turn causes hollow piercers 
20 and 21 to pierce seals (not shown) on disk 11 which cover the ends of 
powder filled cavity 22, thus creating an air passage through cavity 22. 
The air passage is blocked only by dry powder 23, because the tab of 
pierced cavity seal (not shown) is held against the side of cavity 22 by 
hollow piercer 21. Movable section 17 is held in a depressed position 
until the user has inhaled, so that piercers 20 and 21 remain in contact 
with cavity 22. The user inhales air into air passageway 24 through air 
intake end 25 and vents 26. The passage of air through vents 26, hollow 
piercer 20, cavity 22, hollow piercer 21, air intake end 25 and air 
passageway 24, virtually purges powder 23 from cavity 22, carrying it 
along with the user's inspired air into the lungs. 
Referring now to FIGS. 4 through 7, there is shown a multiple dose powder 
dispenser 30 in accordance with the principles of the present invention. 
Dispenser 30 is suitable for use with typical dry powder inhalers known in 
the art. Dispenser 30 is comprised of a first portion 31 and a second 
portion 32, each portion having a plurality of cavities 33, 33' extending 
therethrough. While the invention is not intended to be limited by the 
shape of dispenser 30, first portion 31 and second portion 32 are 
preferably disc-shaped, wherein the plurality of cavities 33, 33' is 
circumferentially placed. First portion 31 and second portion 32 are 
preferably formed of high impact polystyrene, although other materials 
known in the art may also be used. Examples include, conventional molded 
plastics, such as polypropylene, polyethylene, acetal, ABS, injection 
molded thermoplastics and the like. 
Dispenser 30 may be of any given diameter and may contain different numbers 
of cavities, depending on the requirements of the particular drug to be 
used. A preferred multiple-dose dispenser is about 1.9 to 3.2 cm in 
diameter and about 0.6 to 0.8 cm deep. While first portion 31 and second 
portion 32 may be substantially equal in diameter and thickness, they need 
not be. Indeed, one of the advantages of the two-piece construction 
according to the invention is that an asymmetric dispenser may be readily 
fabricated. One or the other of the portions might be somewhat larger in 
diameter, for example, whereby the asymmetry will assist the user in 
recognizing the proper "right-side-up" orientation when dispenser 30 is 
subsequently inserted into a dry powder inhaler. A minor modification of 
dispenser 30, such as a shoulder, can be used such that insertion in an 
improper orientation makes the unit mechanically non-functional. 
Similarly, either portion may include an arrow or other indicator to 
assist in proper functional alignment of dispenser 30 with inhaler 10. 
Each of the cavities 33, 33' in first portion 31 and in second portion 32 
is sealed on one end (the same end for each cavity) by a conventional 
pierceable seal such as, e.g., a plastic film, a metal film, such as 
aluminum foil or a metalized laminate. Sealing one end of cavities 33' in 
second portion 32 thus allows cavities 33' to retain a volume of dry 
powder. In a preferred embodiment of the invention, one of the cavities 
33' in second portion 32 may be sealed or otherwise blocked on each end, 
thus completely blocking the cavity and preventing the subsequent filling 
of the cavity with dry powder. 
Preferably, the volume of each cavity 33' in second portion 32, i.e., from 
the seal to the remaining open end, will be the volume required to retain 
one unit dose of a particular dry powdered drug 34 to be used. This 
facilitates the filling of dispenser 30 with unit doses of a particular 
drug powder 34 in that a bulk volume of the powder can be dropped into the 
powder chambers and the excess scraped away, leveling the powder surface 
and leaving an accurate, non-compacted volume of drug powder 34 in each 
chamber, as shown in FIG. 4. Thus, the typically small volume drug powder 
dosages are assured without the need for the intricate powder handling 
equipment generally necessary to accurately meter these small volumes. 
Following the bonding of first portion 31 to second portion 32, the depth 
of the cavities 33 in first portion 31 provides "head-space" to the sealed 
chambers, further preventing compaction of the drug powder. 
As indicated, the two portions 31, 32 of dispenser 30 are bonded together, 
thus forming a single, integrated unit 30. The two portions 31, 32 are 
bonded together after the cavities 33' in second portion 32 have been 
filled. First portion 31 is positioned over second portion 32, having the 
open ends of cavities 33 and 33' in alignment, and the portions are then 
coupled. As shown in the figures, first portion 31 and second portion 32 
can include corresponding protrusions 35 and receptacles 36 for aiding in 
alignment of the cavities. A preferred coupling method is ultrasonic 
welding which results in an airtight, hermetic seal around each of the 
corresponding cavities 33 and 33'; thus, the powder-filled cavities 33' in 
second portion 32 and the empty cavities 33 in first portion 31 combine to 
form a plurality of individual, hermetically sealed chambers. Preferably, 
the sealed chambers are cylindrically or conically shaped, allowing the 
powder to freely flow from the chamber when the seal is broken during the 
dispensing process. 
To aid in the ultrasonic welding of the individual chambers, surrounding 
each cavity 33' in second portion 32 is a molded raised ring 37. During 
the welding process, ring 37 concentrates and directs the ultrasonic 
energy to itself, thereby rapidly initiating the preferential softening 
and melting of ring 37 to join the two portions 31 and 32 and hermetically 
seal each of the individual chambers. As earlier indicated, portions 31 
and 32 are preferably formed from high impact polystyrene. The 
characteristics of this material provide a superior ultrasonic welding of 
the two portions. 
As previously discussed, one of cavities 33' in second portion 32 may be 
sealed or otherwise blocked at each end, thus preventing this cavity 33' 
from being filled with a dry powder dose 34. This feature provide a means 
for preventing inadvertent "double-dosing" when dispenser 30 is first 
rotatably inserted into a dry powder inhaler 10. Without this feature, the 
user could inadvertently depress the movable portion 17 of cover 12, 
piercing the seal on a powder-filled chamber 22 and releasing some or all 
of a drug dose 23, during the insertion process. The dose 23 would then be 
lost, or the user would rotate the disc 11 to what was believed to be the 
initial dose and release a second dose which could then be inhaled along 
with the residual powder from the inadvertent dispensing. By including an 
unfilled cavity, the multiple-dose dispenser of the present invention 
overcomes this disadvantage. 
Referring now to FIGS. 3 and 4, in one embodiment of the present invention, 
one of first portion 31 (shown) or second portion 32 may include a series 
of ratchet teeth 38 on its outer periphery, for functionally indexing the 
individual chambers into the proper dispensing position when dispenser 30 
is in use with a dry powder inhaler 10. As illustrated, there is one 
ratchet tooth 38 corresponding to all but one sealed chamber, this being 
the chamber wherein the cavity in second portion 32 is sealed on each end, 
and therefore, the chamber does not contain a dose of powder. Thus, when 
the dose in the previous chamber has been administered, dispenser 30 will 
not rotate to the empty chamber. 
Additionally, dispenser 30 may include means, such as tabs 39 on first 
portion 31, for facilitating insertion, removal and rotation of dispenser 
30 with respect to inhaler 10. Dispenser 30 may include reference numerals 
or the like (not shown) corresponding to each of the sealed chambers, 
which are viewable through a window in inhaler 10 and which indicate how 
many doses remain in the dispenser. 
This invention has been described in terms of specific embodiments, set 
forth in detail. It should be understood, however, that these embodiments 
are presented by way of illustration only, and that the invention is not 
necessarily limited thereto. Modifications and variations within the 
spirit and scope of the claims that follow will be readily apparent from 
this disclosure, as those skilled in the art will appreciate.