WO2002078774A1

WO2002078774A1 - Compliance system for drug delivery

Info

Publication number: WO2002078774A1
Application number: PCT/DK2002/000167
Authority: WO
Inventors: Troels Keldmann; Erik Keldmann; Teresa Pallotta
Original assignee: Direct Haler AS
Current assignee: Direct Haler AS
Priority date: 2001-03-28
Filing date: 2002-03-13
Publication date: 2002-10-10
Anticipated expiration: 2003-09-28

Abstract

Compliance system comprising a number of compliance devices, each consisting of two delivery modules for the intake of drugs by pulmonary and/or nasal route. Each module comprises a tubular body for defining an air flow passage. The tubular body comprises two substantially rectilinear sections 1 and at least one intermediate flexible section 2 and contains a dose of a particulate substance. The tubular body is sealed or closed in relation to the ambient atmosphere by means of closure means 4, which are to be removed by the user prior to use. Patients undergoing combination therapy experience problems in everyday life when having to take two or several different drugs at specific times of the day. In connection with drug intake the term 'compliance' expresses how well the patient complies with the treatment prescribed by the doctor. In an attempt to solve this problem, combination drugs have been developed, which are supplied in a multi-dose inhalation device, in which the ratio of the drugs have been predetermined. According to the invention, this problem have been solved by a compliance device consisting of two delivery modules designed such that in their unopened state they are complementary in packaging, the closure means of one inhalation device being clipable onto the other delivery module such that the joined modules may be packed tightly in a transparent packaging and arranged in conventional drug dispensing trays for seven days consumption. This allows the desired combination therapy to be used in such a manner that the patient complies with the treatment prescribed by the doctor at the same time as the device is considerably more compact than known devices.

Description

Title: Compliance system for drug delivery

Technical Field

The invention relates to a compliance system for drug delivery comprising at least one compliance device including a number of delivery modules in form of tubular bodies defining an air flow passage, each of said tubular bodies having substantially rectilinear sections and at least one intermediate flexible section and containing a dose of an active particulate substance for nasal or pulmonary delivery arranged in the flow passage, said dose being sealed or closed in relation to the ambient atmosphere by means of closure means which are to be removed by the user prior to use.

Background Art

Such delivery modules for inhalation or insufflation are inter alia described in WO 96/22802 and WO 98/53869.

Todays research have shown that patients undergoing combination therapy have problems in everyday life with taking two or several different drugs. In connection with intake of drugs the term "compliance" expresses how well the patient complies with the treatment prescribed by the doctor, ie taking the correct drug in the correct amount at the correct time(s).

An example of the above occurs in connection with the treatment of respiratory diseases (asthma and chronic obstructive pulmonary disease) in which a combination of long-acting beta₂-agonist and corticosteroid is used, where the patient often has to use two multi-dose (200 doses) inhalation devices, each containing a separate drug for inhalation. The combination therapy is advantageous inter alia due to the improved effect and reduced adverse effects. However, if the drug is stored in two or more different multi-dose devices the patient has to be very conscientious and self-disciplin- ed to achieve the optimum result of the combination therapy. The task in hand is thus taking the correct drug and the correct combination in the correct dose at the correct time. In an attempt to improve the use-value a combination drag has been developed which is supplied in a multi-dose inhalation device (200 doses), in which the ratio between the different drugs has been predetermined.

One of the drawbacks of the known inhalers is, however, that they are comparatively bulky. In addition hereto it is not possible to ascertain whether the prescribed doses in fact have been taken by the patient.

Brief Description of the invention

The object of the invention is to show how to design the said compliance device in a more compact manner than hitherto known and at the same time rendering the desired combination therapy possible. Furthermore the said compliance device is designed so as to easily check whether the prescribed doses in fact have been taken by the patient. Another advantage is that it is possible to take the two different formulations separately, which may be of importance for the effect.

Another object of the invention is to provide a compliance device comprising compact packed delivery modules.

A further object of the invention is to provide an integrated compliance system com- prising a number of compact packed compliance devices.

According to the invention the said delivery modules are formed such that in their unopened state they are complementary in packaging, the closure means of one of the delivery modules being clipable onto the other delivery module such that the joined delivery modules may be packed tightly. In addition hereto the devices are very com- pact, in fact so compact that they may be used in connection with pill dispensing trays comprising seven small compartments for seven days' consumption which for instance are used in nursing homes. Moreover, by packing the transparent joined delivery modules in transparent packagings it is possible to check whether the dose prescribed by the doctor in fact has been taken.

In a particularly advantageous embodiment the delivery modules are U-shaped in their unopened state, the U-shaped state being maintained by means of the closure means.

Furthermore according to the invention each closure means is formed of two closure caps or closure foils interconnected by means of at least one connecting flap.

Finally according to the invention the connecting flap may be arranged such and be of such a length that a tubular body of the second delivery module may be snugly received and retained between the caps, whereby two U-shaped delivery modules may be clipped onto each other such that the U-shape of one delivery module faces opposite to the other delivery module.

Brief Description of the drawing

The invention is explained in greater detail below with reference to the accompanying drawings, in which

fig. 1 illustrates a compliance device consisting of a set of delivery modules according to the invention,

fig. 2 is an end view of one of a closure means for a delivery module,

fig. 3 is a perspective view of a closure means for a delivery module,

fig. 4 illustrates another embodiment of a closure means, fig. 5 illustrates the compliance device consisting of delivery modules arranged in a transparent packaging,

fig. 6 illustrates a number of packed compliance devices arranged in a pill dispensing tray for seven days' consumption,

fig. 7 illustrates an alternative embodiment of the pill dispensing tray shown in Fig. 6,

fig. 8 illustrates a compliance device comprising two delivery modules for simultaneous intake of two particulate substances,

fig. 9 A, 9B and 9C illustrate examples of closure means for the compliance device of fig. 8,

fig. 10 illustrates the compliance device of fig. 8 with an additional mouthpiece facilitating the simultaneous intake of two particulate substances, and

fig. 11 illustrates the compliance device of fig. 10 with an associated closure means.

Best Mode for Carrying out the Invention

The present invention is based on the idea that the two drugs prescribed for a combina- tion therapy are contained in two separate delivery modules. The invention deals with ensuring an optimum use- value of and comfort during combination therapy at the pulmonary and/or nasal delivery.

The set of delivery modules shown on the drawing for taking medicine is formed of two substantially U-shaped tubular bodies. Each of the tubular bodies comprises two substantially rectilinear sections 1 and at least one intermediate flexible section 2. A dose of a particulate substance for nasal or pulmonary delivery is further contained in the flexible section 2, said dose being sealed or closed in relation to the ambient atmosphere by means of closure means, which are to be removed by the user prior to use.

According to the invention the said delivery modules are formed such that in their unopened state they are complementary in packaging, the closure means of one of the delivery modules being clipable onto the other delivery module such that the joined delivery modules may be packed in a tight manner. The delivery modules are U-shaped in their unopened state, the U-shaped state being maintained by means of the closure means 4. Each closure means 4 may for instance be formed of two closure caps or closure foils interconnected by means of at least one connecting flap 7 (confer fig. 4). The connecting flap 7 may be formed such that in the mounted state of the closure means 4 the second delivery module may be snugly received and retained between the caps, whereby the two U-shaped delivery modules may be clipped onto each other such that the U-shape of one delivery module faces opposite to the other delivery module.

An embodiment of the invention may be a folding action of two delivery modules, each containing a dose of two separate drugs. The folding action allows for a joint packing of two modules, whereby the device comprising said modules becomes compact. Since two different drugs are involved, which have to be taken in the correct order, the delivery modules are differentiated from each other by the design of the caps and their colours such that the user may see and feel a difference between the two "doses".

It is also part of the invention that the caps and each of the delivery modules are designed such that the two delivery modules may be clipped onto each other and thus only exceed the size of a single delivery module by about 41%.

The joined modules are enclosed by a protective packaging 5, which is transparent on one side, whereby the two doses are visible, providing the patient with a sense of security. The other side of the packaging 5 may optionally be supplied with the necessary information (optionally in form of bar codes), such as the day of the week, the dose, content, user instructions, expiry date, etc.

Another embodiment of the pulmonary compliance device is a device, in which one module is intended for the upper respiratory passages and the other is intended for the lowerrespiratorypassages. This requires different powder formulations for each target. It is thus a new option for packing two delivery modules together, each having its own powder formulation and thus its own delivery target.

It is also possible to use the same type of delivery modules for both pulmonary and nasal drug intake. The compliance device according to the invention may thus also comprise a nasal delivery module and a pulmonary delivery module. This combination of two delivery modules makes it possible to cover both types of respiratory delivery of the drag. This may be important in relation to future drags used for strengthening the immune response in the respiratory passages. As an example it may be possible to stimulate the immune defense of the cell in the mucous membranes by means of inhalable drugs.

Since the nasal compliance device has the same design as the above device, two nasal delivery modules may also be clipped onto each other as described above. Two nasal doses may also be used for a combination therapy in which two different drugs have to be delivered to either nostrils or the same drag has to be delivered to the same nostril.

A further embodiment relates to cases where only one dose of a very expensive substance, eg a vaccine, is needed. In such cases the other delivery module may be used for training and delivery of a placebo powder.

The compliance device may be considered as an "inhalation pill" which allows for an administration system combining the advantages of certain pill-dispensing packing systems with an efficient inhalation therapy. The suggested packaging concept also allows for printing of the inhalation doses for a predetermined dosage schedule, according to which each combined device must be taken at a specific time and the dose concentration is different for each of the packed combined devices. This type of dose "programming" is known from contraceptive pills, where the dose and the timing are vital and where the packaging assists the patient in obtaining compliance.

The unit dose dispensing of drags from a pharmacy to the patients is a new way of assisting the patients in taking the correct drug at the correct time. It is intended that pharmacies in the future are able to pack drugs in units such that the drug is packed per time of intake, eg four doses to be taken at noon, and two doses at bedtime, each day for fourteen days. The invention will make such a type of device dispensing possible for inhalation and/or insufflation products. This will also be vital within the hospital services.

Fig. 6 illustrates a compliance system comprising a number of packed compliance devices arranged together with any pills in a pill dispensing tray comprising seven small compartments for seven days' consumption.

Fig. 7 illustrates an alternative embodiment of the pill dispensing tray shown in fig. 6, in which the packagings containing the tightly packed compliance devices are arranged vertically in a box, which may be closed by means of a lid. In this case it is also easily checked whether the patient has remembered to take the prescribed drug doses.

The pill dispensing tray shown in fig. 5 and the box shown in fig. 7 may for instance be packed so as to enable a degree of periodic drag intake, some of the compliance devices for example containing higher drag doses than others.

In special cases, a person may be interested in a simultaneous intake of two or more particulate substances. For this purpose, two delivery modules may be firmly interconnected, each individual delivery module containing separate particulate substances, in special cases, the same particulate substance, if the meaning merely is that the patient should have the double dose. The two interconnected modules, cf fig. 8, are thus closed by means of a common closure means prior to use. Figs. 9A, 9B and 9C illustrate examples of different closure means. The closure means illustrated in fig. 9A is de- signed to delivery modules, in which the one end projects slightly than the other end and essentially corresponds to two closure means of the type illustrated in fig. 3 in one piece. The closure means illustrated in fig. 9B is intended for an embodiment of the said delivery modules, in which the ends flush. The same applies to the closure means illustrated in fig.9C comprising a number of interconnected spherical bodies for inser- tion into and closing of the tubular bodies.

To facilitate the simultaneous intake of several preparations, a mouthpiece may advantageously be mounted on the two delivery modules as illustrated in fig. 10, in which case, a special closure means is required. Said closure means comprise caps in one piece or the like, closely fitting the joint mouthpiece and the ends of the said delivery modules, respectively, cf fig. 11.

Claims

1. A compliance system for drag delivery comprising at least one compliance device including a number of delivery modules in form of tubular bodies defining an air flow passage, each of said tubular bodies having substantially rectilinear sections (1) and at least one intermediate flexible section (2) and containing a dose of an active, particulate substance for nasal and/or pulmonary delivery arranged in the flow passage, said dose being sealed or closed in relation to the ambient atmosphere by means of closure means (4), which are to be removed by the user prior to use, characterised in that the said delivery modules are formed such that in their unopened state they are complementary in packaging (Fig 1), the closure means (4) of one of the delivery modules being clipable onto the other delivery module such that the joined delivery modules may be packed tightly.

2. Compliance system according to claim 1, characterised in that the compliance device consists of tightly packed and substantially transparent delivery modules are arranged in a packaging preferably made from a transparent material.

3. Compliance system according to claim 2, characterised in that the packaging is provided with instructions such as the time of nasal and/or pulmonary delivery.

4. Compliance system according to claim 1, characterised in that the delivery modules are U-shaped in unopened state.

5. Compliance system according to claim 3, characterised in that the U-shaped state is maintained by means of the closure means (4).

6. Compliance system according to one of the claims 1-4, characterised in that each closure means (4) is formed of two closure caps or closure foils interconnected by means of at least one connecting flap (7).

7. Compliance system comprising a number of compliance devices, characterised in that the connecting flap (7) is arranged such and of such a length that a tubular body of the second delivery module is received snugly and retained between the caps, whereby two U-shaped delivery modules may be clipped onto each other such that the U-shape of one delivery module faces opposite to the other delivery module.

8. Compliance system comprising a number of compliance devices, characterised in that one delivery module contains a predetermined dose of one drag, while the other delivery module contains another predetermined dose of another drug.

9. Compliance system comprising a number of compliance devices, character- i s e d in that one delivery module contains a predetermined dose of a drug in a first formulation, while the other delivery module contains the same drag in a different formulation.

10. Compliance system comprising a number of compliance devices, characterised in that one delivery module is intended for nasal delivery via a nostril, while the other delivery module is intended for pulmonary delivery via the oral cavity.

11. Compliance system comprising a number of compliance devices, characterised in that one delivery module contains a placebo for training purposes and the other delivery module contains the drag per se.

12. Compliance system comprising a number of compliance devices, each comprising two delivery modules in form of tubular bodies defining an air flow passage, each of said tubular bodies having substantially rectilinear sections (1) and at least one intermediate flexible section (2) and containing a dose of an active, inhalable, particulate substance arranged in the flow passage, said dose being sealed or closed in relation to the ambient atmosphere by means of closure means (4), which are to be removed by the user prior to use, characterised in that the said delivery modules are formed such that in their unopened state they are complementary in packaging (Fig 1), the closure means (4) of one of the delivery modules being clipable onto the other delivery module such that the joined delivery modules may be packed tightly.

13. Compliance system comprising a number of compliance devices, char- acterisedby each compliance device consisting in two delivery modules firmly interconnected for a simultaneous intake of two preparations, said preparations preferably being different.