WO2003020197A1

WO2003020197A1 - Improvements in or relating to the delivery of oral drugs

Info

Publication number: WO2003020197A1
Application number: PCT/IB2002/003590
Authority: WO
Inventors: Michael Tobyn; John Staniforth; David Bradley Brook Simpson; Graeme Lindsay Jonathan Paterson; Christopher Althorpe
Original assignee: Vectura Limited
Priority date: 2001-09-05
Filing date: 2002-09-04
Publication date: 2003-03-13

Abstract

A drug delivery device and method for administering a multiparticulate therapeutic agent into an oral cavity of a human patient for gastrointestinal deposition. The device includes a housing, a delivery unit, a metering unit and an actuator. The housing define a reservoir capable of containing multiple doses of the therapeutic agent. The delivery unit defines a delivery receptacle, is moveable between a closed position and an extended position, and is capable of delivering a unit dose of the therapeutic agent into the oral cavity when the delivery unit is in the extended position. The metering unit defines a dose receptacle and is moveable between a loading position, in which the dose receptacle communicates with the reservoir, and an unloading position, in which the dose receptacle communicates with the delivery receptacle when the delivery unit is in the closed position. The actuator, upon actuation, causes the metering unit to move from the loading to the unloading position so as to meter the unit dose and move the unit dose from the reservoir to the delivery receptacle. The actuator also prevents the delivery unit from being moved from the closed position until after the metering unit has moved from the loading to the unloading position.

Description

IMPROVEMENTS IN OR RELATING TO THE DELIVERY OF ORAL DRUGS

FIELD OF THE INVENTION

The present is directed to a drug delivery device, system and method for the oral administration of a multiparticulate therapeutic agent into the oral cavity of a mammal for gastrointestinal deposition.

BACKGROUND OF THE INVENTION

The most prominent mode of delivery of therapeutic agents is by the oral route by means of solid dosage forms such as tablets and capsules. Oral administration of solid dosage forms is more convenient and accepted than other modes of administration, e.g. parenteral administration. However, the manufacture, dispensing and administration of solid dosage forms are not without associated problems and drawbacks.

With the manufacture of solid dosage forms, in addition to the active agent, it is necessary to combine other ingredients in the formulations for various reasons, such as to enhance physical appearance, to provide necessary bulk for tableting or capsuling, to improve stability, to improve compressibility or to aid in disintegration after administration. However, these added excipients have been shown to adversely influence the release, stability and bioavailability of the active ingredient. The added excipients are a particular problem with drugs that require a high dose in order to provide a therapeutic effect, e.g., biphosphonate drugs. The inclusion of the additional excipient can make the final tablet extremely large, which could result in esophogeal damage if the dosage form is not swallowed properly.

Further, the tableting of certain drugs has many associated production problems. In particular, many drugs, e.g., acetaminophen, have poor compressibility and cannot be directly compressible into solid dosage forms. Consequently, such drugs must either be wet granulated or manufactured in a special grade in order to be tableted which increases manufacturing steps and production costs.

The adherence to good manufacturing practices and process controls is essential in order to minimize dosage form to dosage form and batch-to-batch variations of the final product. Even strict adherence to these practices still is not a guarantee that acceptable variation will occur. With the high cost of industrial scale production and governmental approval of solid dosage forms, such foπnulations are often available in a limited number of strengths, which only meet the needs of the largest sectors of the population. Unfortunately, this practice leaves many patients without acceptable means of treatment and physicians in a quandary with respect to individualizing dosages to meet the clinical needs of their patients.

The dispensing of oral solid dosage forms also makes the formulations susceptible to degradation and contamination due to repackaging, improper storage and manual handling.

There are also many patients who are unable or unwilling to take conventional orally administered dosage forms. For some patients, the perception of unacceptable taste or mouth feel of a dose of medicine leads to a gag reflex action that makes swallowing difficult or impossible. Other patients, e.g., pediatric and geriatric patients, find it difficult to ingest typical solid oral dosage forms, e.g., due to tablet size.

Other patients, particularly elderly patients, have conditions such as achlorhydria, which hinders the successful use of oral solid dosage forms. Achlorhydria is a condition wherein there is an abnormal deficiency or absence of free hydrochloric acid in the gastric secretions of the stomach. This condition hinders the disintegration and/or dissolution of oral solid dosage forms, particularly dosage forms with high or insoluble excipient payloads

Flavored solutions/suspensions of some therapeutic agents have been developed to facilitate the oral administration of oral agents to patients normally having difficulty ingesting conventional solid oral dosage forms. While liquid formulations are more easily administered to the problem patient, liquid/suspension formulations are not without their own significant problems and restrictions. The liquid dose amount is not as easily controlled compared with tablet and capsule forms and many therapeutic agents are not sufficiently stable in solution/suspension form. Indeed, most suspension type formulations are typically reconstituted by the pharmacist and then have a limited shelf life even under refrigerated conditions. Another problem with liquid formulations, which is not as much a factor with tablets and capsules, is the taste of the active agent. The taste of some therapeutic agents is so unacceptable that liquid foπnulations are not a viable option. Further, solution/suspension type formulations are typically not acceptable where the active agent must be provided with a protective coaling, e.g. a taste masking coating or an enteric coating to protect the active agent from the strongly acidic conditions of the stomach.

Another alternative to oral dosage forms for certain medications is aerosol dosage forms, which administer therapeutic agents for deposition to the pulmonary system. The use of aerosol dosage foπns has many advantages for the patient. The packaging of the active agent is convenient and easy to use, generally with limited manual manipulation. As the medicine is sealed within the device, direct handling of the medication is eliminated and the contamination of the contents from air and moisture can be kept to a minimum. Further, a metering valve can be included in the device in order to individualize the dose for particular patients. However, such formulations also have drawbacks such as decreased bioavailability of the drug due to improper administration by the patient. For example, if a patient's breathing is not coordinated with the activation of the device, the active agent will not reach its intended site of action which will lead to a decrease in therapeutic benefit.

Another alternative is dry powder dosage forms. For example, International Patent Application WO 94/04133, hereby incorporated by reference, describes a powder composition for inhalation, which contains a microfine drug such as salbutamol sulfate and a carrier containing an anti-static agent. The carrier is calcium carbonate or a sugar, especially lactose. The amount of carrier is 95-99.99 weight percent. The compositions are said to be useful for delivery of the active agent to the lungs while providing reduced side effects such as nausea by maximizing its proportion of drug reaching the lungs.

U.S. Pat. No. 4,590,206, hereby incorporated by reference, describes capsules, cartridges or aerosol containers containing spray-dried sodium cromoglycate in finely divided and un-agglomerated form. A substantial proportion of the individual drug particles have sizes and shapes, which allow deep penetration into the lung and yet are free-flowing so as to allow capsule filling.

International Patent Application WO 93/25198, hereby incorporated by reference, is directed to an ultrafme powder for inhalation. The powder comprises a drug and hydroxypropyl cellulose and/or hydroxypropylmethylcellulose. More than 80 weight percent of the particles in the powder are said to have a particle diameter of 0.5-10 microns. The powder is said to be able to reach the lower windpipe and bronchi. Due to the disadvantages of known drug delivery discussed above (as well as other disadvantages) there exists a need in the art for the development of a device and method for facilitating delivery of a wide range of therapeutic agents for gastrointestinal deposition and which minimize pulmonary deposition of materials having undesirable or unknown pulmonary toxicology but which are approved for oral delivery.

Oral drug delivery systems, devices and methods for oral powders are disclosed in PCT/IBO 1/00251, hereby incorporated by reference in its entirety for all purposes.

OBJECTS OF THE INVENTION

It is an object of the invention to provide a method, device and system for the delivery of a dose of a therapeutic agent in multiparticulate form for gastrointestinal deposition.

It is an object of the invention to provide a method, device and system for the oral administration of a dose of a therapeutic agent in multiparticulate form into the oral cavity of a patient for gastrointestinal deposition.

It is an object of the invention to provide a method, device and system for the dispensing of a dose of a therapeutic agent in multiparticulate form, for subsequent administration into the oral cavity for gastrointestinal deposition.

It is a further object of the invention to provide a method, device and system for delivery of multiple doses of a therapeutic agent in multiparticulate form, which minimizes the need for inert pharmaceutical excipients.

It is a further object of the invention to provide a method, device and system for delivery of multiple doses of a therapeutic agent in multiparticulate form for fast, standard, sustained, controlled, or targeted release.

It is a further object of the invention to provide a method, device and system for the delivery of a dose of a therapeutic agent for gastrointestinal deposition, which protects the active ingredient from contamination and moisture.

It is a further object of the invention to provide a method, device and system for the delivery of a dose of a therapeutic agent for gastrointestinal deposition, which allows for the dosing to be adjustable based on the needs of an individual patient or patient population. It is a further object of the invention to provide a method, device and system for the delivery of a dose of a therapeutic agent for gastrointestinal deposition, which can be used for a wide variety of agents for a wide variety of therapies, e.g. to treat systemic and/or local conditions.

It is a further object of the invention to provide a method, device and system for the delivery of a dose of a therapeutic agent for gastrointestinal deposition, which provides an acceptable variability from dose to dose and batch to batch.

It is a further object of the invention to provide a method of producing a unit dose of a drug without limitation to the compressibility or dose amount of the drug.

It is a further object of the invention to provide a method and system for the delivery of a dose of a therapeutic agent for gastrointestinal absorption, which can be administered and swallowed without the aid of a fluid.

It is a further object of the invention to provide a method and device for the delivery of a dose of a multiparticulate therapeutic agent, in which the device can be positioned substantially below the mouth of the patient during actuation.

It is a further object of the invention to provide a method and device for the delivery of a dose of a multiparticulate therapeutic agent, in which the actuator of the device can be equally accessible by the patient for self-administration and/or by a caregiver for administration to another.

The above objects of the invention and others are achieved by virtue of the present invention, which in certain embodiments provides a drug delivery system for delivery of a drug for gastrointestinal deposition.

SUMMARY OF THE INVENTION

The present invention provides a drug delivery device for administering a multiparticulate therapeutic agent into an oral cavity of a human patient for gastrointestinal deposition. The device includes a housing, a delivery unit, a metering unit and an actuator. The housing defines a reservoir capable of containing multiple doses of the therapeutic agent. The delivery unit defines a delivery receptacle, is moveable between a closed position and an extended position, and is capable of delivering a unit dose of the therapeutic agent into the oral cavity when the delivery unit is in the extended position. The metering unit defining a dose receptacle and is moveable between a loading position, in which the dose receptacle communicates with the reservoir, and an unloading position, in winch the dose receptacle communicates with the delivery receptacle when the delivery unit is in the closed position. The actuator, upon actuation, is capable of causing the metering unit to move from the loading to the unloading position so as to meter the unit dose and move the unit dose from the reservoir to the delivery receptacle, and the actuator prevents the delivery unit from being moved from the closed position until after the metering unit has moved from the loading to the unloading position.

The drug delivery device may be used together with a multiparticulate therapeutic agent that includes drug particles having a mean diameter of greater than 10 μm and less than 1 mm. In certain embodiments, when the delivery unit is in the extended position, the delivery receptacle is above the metering unit. The delivery unit may be pivotably mounted to the housing, and/or removably attached to the housing. The delivery receptacle may be capable of delivering the unit dose using a movement of air within the delivery receptacle.

In certain embodiments, the delivery unit may further define an outlet passage having a funnel shape so as to cause an acceleration or a deceleration of drug particles of the multiparticulate therapeutic agent during a delivery of the unit dose to the oral cavity.

The actuator may include a lever and a linkage between the lever and the metering unit, wherein the lever prevents the delivery unit from moving from the closed position until after the metering unit has moved from the loading to the unloading position. The drug delivery device may further include a waste container defining an opening, wherein the delivery receptacle is capable of communicating with the opening of the waste container when the delivery unit is in the closed position.

In certain embodiments, the delivery unit may include a delivery housing defining a delivery outlet and a waste outlet and may further include a flexible inner tube rotatablc about an axis defined by the flexible inner tube within the delivery unit. A rotation of the flexible inner tube may effect a movement of the delivery receptacle between a delivery position, in which the delivery receptacle communicates with the delivery outlet, a waste position, in winch the delivery receptacle communicates with the waste outlet, and a shut position, in which the delivery receptacle does not communicate with either the delivery or waste outlets. A cover may be removably disposed on the housing and capable of covering at least one of the delivery outlet and the waste outlet of the delivery unit when the delivery unit is in the closed position. In certain embodiments a cover might perform the function of the actuator, and thus the actuator may be capable of covering at least one of the delivery outlet and the waste outlet of the delivery unit when the delivery unit is in the closed position.

The metering unit may include a drum-shaped body defining the dose receptacle and rotatably mounted within a sleeve having a loading opening and an unloading opening. The dose receptacle may cornmunicate with the loading opening when the metering unit is in the loading position and may communicate with the unloading receptacle when the metering unit is in the unloading position. The reservoir may define, at its lower end, an exit opening communicating with the loading opening so that a rotation of the body witlnn the sleeve is capable of metering a unit dose of the therapeutic agent from the multiple doses of the therapeutic agent in the reservoir.

The housing may further define an inteπnediate passage communicating with the unloading opening of the sleeve capable of providing communication between the dose receptacle and the delivery receptacle.

The delivery unit may be capable of delivering the unit dose to a tongue of the oral cavity when the delivery unit is in the extended position. The actuator may be further capable of effecting delivery of the unit dose from the delivery unit to the oral cavity and may be further capable of moving the metering unit from the unloading position back again to the loading position. Upon a subsequent actuation the actuator may be capable of causing the metering unit to move from the loading to the unloading position so as to meter a second unit dose and move the second unit dose from the reservoir to the delivery receptacle.

In order to promote patient compliance, certain embodiments of the invention include a counter which indicates the number of doses actuated. Alternatively, the dosing device can include an indicator to display the number of doses remaining in the dosing device. The ability to count remaining doses is useful especially to a patient who may have forgotten if a previous dose has been taken. A counter also minimizes the likelihood of the patient miscounting the proper dosage and taking a double dose or skipping a dose due. The counter will also keep the user apprized as to when the drug will run out and will help to improve patient compliance by allowing for proper planning for the patient to frequent a pharmacy in a timely manner. This can reduce the likelihood of a patient being "surprised" when the system does not provide any unit doses. The device can alternatively count the doses delivered by counting up, or can count down to show the number of unit doses remaining in the system. The counter can be an electrical or mechanical mechanism which are commonly known in the art. The indicator can also be a visual mechanism, e.g., the formulation could fall below a colored marker which would indicate the number of doses remaining, the device can expose the internal formulation to view in a window, or other mechanisms known in the art. In certain embodiments, the unit doses can be premetered in individual packaging, e.g., a blister pack. In such embodiments, the dosecounting mechanism can comprise having numbers printed onto each premetered package which can be displayed to show the doses actuated or the remaining doses.

The device may also include a second actuator capable of propelling the unit dose from the delivery unit to the oral cavity. The second actuator may be capable of propelling the unit dose and may use forced air, a catapult mechanism, or gravity.

The present invention also provides a method for administering a multiparticulate therapeutic agent into an oral cavity of a human patient for gastrointestinal deposition. The method includes using an actuator to move a metering unit defining a dose receptacle from a loading position in which the dose receptacle communicates with a reservoir containing multiple doses of the therapeutic agent to an unloading position, in which the dose receptacle communicates with a deliveiy receptacle, the moving of the metering unit from the loading position to the unloading position effecting a metering of the unit dose and moving the unit dose from the reservoir to a delivery receptacle of a delivery unit. The method also includes moving the deliveiy unit from a closed position to an extended position after the actuating of the actuator. The method also includes delivering the unit dose from the delivery unit into the oral cavity.

The method may be used together with a therapeutic agent wherein the unit dose includes drug particles having a mean diameter of greater than 10 μm and less than 1 mm.

The opening of the delivery unit may include moving the delivery unit so that the delivering receptacle is above the metering unit and/or may include pivoting the delivery unit on the housing.

The delivering of the unit dose may be performed using a movement of air within the delivery receptacle and/or may include accelerating or decelerating drug particles of the unit dose using a funnel shape defined by an outlet passage of the delivery unit.

The method may also include closing the delivery unit after the delivering of the unit dose so as td enable the delivery receptacle to communicate with a waste container and or rotating a flexible inner tube of the delivery unit so as to effect a movement of the delivery receptacle between a delivery position, in which the delivery receptacle communicates with the delivery outlet, a waste position, in which the delivery receptacle communicates with the waste outlet, and a shut position, in which the delivery receptacle does not communicate with either the delivery or waste outlets.

The method may also include covering at least one of the delivery outlet and the waste outlet of the delivery unit using a cover (or using the actuator) when the delivery unit is in the closed position.

The delivering of the unit dose may be performed so as to deliver the unit dose to a tongue of the oral cavity when the delivery unit is in the extended position, and/ or may be performed using the actuator

The method may also include moving the metering unit from the unloading position back again to the loading position and/or causing the metering unit to move from the loading to the unloading position so as to meter a second unit dose and move the second unit dose from the reservoir to the delivery receptacle using a subsequent actuation of the actuator. The method may also include counting a number of unit doses moved from the reservoir using a counter.

The delivery of the unit dose may be performed using a second actuator so as to propel the unit dose from the delivery unit to the oral cavity and may use forced air, a catapult mechanism, or gravity.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following, the present invention will be elaborated upon wiuVreference to the drawings, in which:

Fig. 1 shows a cross-sectional view of one embodiment of a drug delivery device according to the present invention in a non-actuated state;

Fig. 2 shows a cross-sectional view of the drug delivery device of Fig. 1 in a fully actuated state; Fig. 3 shows a perspective view of the drug delivery device of Fig. 1 in a non- actuated state;

Fig. 4 shows a perspective view of the drug delivery device of Fig. 1 in a non- actuated state with a portion of the delivery housing removed;

Fig. 5 shows a perspective view of the drug delivery device of Fig. 1 in a partially actuated state;

Fig. 6 shows a perspective view of the drug delivery device of Fig. 1 in a further partially actuated state;

Fig. 7 shows a perspective view of the drug delivery device of Fig. 1 in a fully actuated state with the delivery unit in a closed position;

Fig. 8 shows a perspective view of the drug delivery device of Fig. 1 in a fully actuated state with the delivery unit in an extended position and the delivery receptacle in a shut position;

Fig. 9 shows a perspective view of the drug delivery device of Fig. 1 in a fully actuated state with the delivery unit in an extended position and the delivery receptacle in a delivery position;

Figs. 10a and 10b show perspective views of a second and a third embodiment of drug delivery devices according to the present invention;

Figs. 1 la and 1 lb show perspective views of a fourth embodiment of a drug delivery device according to the present invention;

Figs. 12a and 12b show perspective views of a fifth embodiment of a drug deliveiy device according to the present invention;

Fig. 13 shows a perspective view of a sixth embodiment of a drug delivery device according to the present invention;

Figs. 14a and 14b show perspective views of a seventh embodiment of a drug delivery device according to the present invention;

Fig. 15 shows a perspective view of an eighth embodiment of a drug delivery device according to the present invention;

Fig. 16 shows a perspective view of a ninth embodiment of a drug delivery device according to the present invention;

Figs. 17a, 17b, and 17c show perspective views of a tenth embodiment of a drug delivery device according to the present invention;

Figs. 18a, 18b, and 18c show perspective views of an eleventh embodiment of a drug delivery device according to the present invention; Figs. 19a and 19b show perspective views of a twelfth embodiment of a drug deliveiy device according to the present invention; and

Figs. 20a - 20f show perspective views of a thirteenth embodiment of a drug deliveiy device according to the present invention.

DETAILED DESCRIPTION

With reference to the embodiment shown in Fig. 1, drug delivery device 10 includes housing 11, which defines reservoir 12 containing a supply (i.e. multiple doses) of multiparticulate therapeutic agent 13. The reservoir may include a cone- shaped region and have an exit opening 31 at its lower end to assist in guiding the multiparticulate therapeutic agent 13 toward exit opening 31. Underneath reservoir 13 is metering unit 16, which may include a drum-shaped body rotatable within sleeve 32 and defining dose receptacle 17. Metering unit 16 is shown in its loading position with dose receptacle 17 facing upward and in communication with reservoir 13 via exit opening 31. Dose receptacle 17 may be sized corresponding to the desired dose amount, so that when in the loading position the amount of multiparticulate therapeutic agent 13 that falls into dose receptacle 17 from reservoir 13 will correspond to the desired dose amount. Actuator 18, which may include lever 19 and linkage 20, is configured so that, upon actuation, metering device 16 moves from the loading position to an unloading position (shown in Fig. 2).

Referring to Fig. 2, delivery device 10 is shown with lever 19 fully actuated and metering unit 16 in the unloading position so that dose receptacle 17 communicates with intemiediate passage 35 of housing 11. Delivery unit 14 includes delivery housing 23 and flexible inner tube 26. Delivery housing defines delivery outlet 24, winch communicates with intermediate passage 35, and waste outlet 25, which communicates with waste container 21 via opening 22 of waste container 21. Delivery unit 14 is pivotably connected to housing 11 at delivery pivot point 38. Deliveiy unit 14 includes delivery receptacle 15, which, as shown in Fig. 2, communicates with dose receptacle 17 via intermediate passage 35. In actuating actuator 18 by moving lever 19, linkage 20 moves metering unit 16 from the loading position (in the non-actuated state shown in Fig. 1) to the unloading position (in the fully actuated state shown in Fig. 2). As metering unit 16 rotates within sleeve 32, dose receptacle 17 comes out of communication with loading opening 33 and reservoir 12, thus metering a u t dose of therapeutic agent 13 according to the size of dose receptacle 17 within sleeve 32. As metering unit 16 further rotates witlnn sleeve 32, it comes into the loading position and dose receptacle 17 comes into communication with unloading opening 34 and intermediate passage 35, and the umt dose of therapeutic agent 13 falls into intermediate passage 35. In addition, the actuation rotates inner tube 23 of delivery unit 14 so that delivery receptacle 15 moves from a waste position, in which delivery receptacle 15 communicates with waste outlet 25 of delivery housing 23 (shown in Fig. 1) to a delivery position, in which delivery receptacle 15 communicates with delivery outlet 24 of delivery housing 23 (shown in Fig. 2). Delivery receptacle 15 preferably reaches its delivery position simultaneously with, or before, dose receptacle 17 comes into communication with intermediate passage 35 so that the unit dose of therapeutic agent 13 falls into delivery receptacle 15 when metering unit 16 reaches its unloading position.

In both Figs. 1 and 2, delivery unit 14 is shown in its closed position. Drug delivery device 10 also includes cover 27, which is removably connected to housing 11 at hinge point 28. hi its closed position, cover 27 covers delivery unit 14 and both waste outlet 25 and delivery outlet 24 of delivery housing 23. Cover 27 may be opened to allow access to delivery unit 14, for example by pivoting cover 27 about hinge point 28. When cover 27 is opened, delivery unit may be moved from its closed position to an extended position (shown, for example, in Figs. 8 and 9) by pivoting delivery unit 14 about its pivot point 38. Cover 27 is shown in the closed position in Figs. 1 and 2.

Figs. 3-9 show perspective views of drug delivery device 10 shown in Figs. 1 and 2. Cover 27 and waste container 21 are not shown in Figs. 3-9 for clarity purposes. Fig. 3 shows the device in a non-actuated state with delivery unit 14 in the closed position and actuator 18 in the non-actuated position.

Fig. 4 likewise shows drug delivery device 10 in a non-actuated state with a portion of delivery housing 23 removed to reveal flexible inner tube 26 and delivery receptacle 15 communicating with waste outlet 25 of delivery housing 23. Lever 19 of actuator 18 is shown to be configured in a partial hook shape around the exterior of delivery housing 23 of deliveiy unit 14. This configuration prevents delivery unit 14 from moving out of its closed position.

Fig. 5 shows drug delivery device 10 in a partially actuated state with lever 19 of actuator 18 moved from its non-actuated position. The movement of lever 19 to this point causes flexible inner tube 26 of delivery unit 14 to rotate so that delivery receptacle 15 no longer communicates with waste outlet 25, but rather is in a shut position and is shut by delivery housing 23.

Fig. 6 shows drug delivery device 10 in a state in which lever 19 of actuator

18 is moved further from its non-actuated position. In this position actuator 18 has caused flexible inner tube 26 of delivery unit 14 to rotate further so that delivery receptacle 15 communicates with intermediate passage 34. In addition, the movement to this position of actuator 18 has caused metering unit 16 to rotate to its unloading position so that dose receptacle 17 is likewise in communication with intermediated passage 34, and thus also in communication with delivery receptacle 15. At this point, gravity causes the unit dose of therapeutic agent 13 to fall from dose receptacle 17 into delivery receptacle 15.

Fig. 7 shows drug delivery device 10 in its fully actuated state, in which lever

19 of actuator 18 has been moved to its fully actuated position. At this point, lever 19 has been moved beyond the far end of delivery unit 14 and the partial hook shape of lever 19 no longer prevents delivery unit 14 from its closed position. Delivery receptacle 15 has been moved to a shut position in which it no loriger communicates with delivery outlet 24, but rather is shut by delivery housing 23. In this manner, the unit dose of therapeutic agent 13 will not fall out of delivery receptacle 15 before it is ready to be delivered into the mouth of a patient.

Fig. 8 shows drug delivery device 10 with delivery unit 14 shown in its extended position represented by reference number 29. Reference number 30 indicates the closed position of deliveiy unit 14 (shown here in dashed lines). Delivery receptacle is in a shut position and is shut by delivery housing 23.

Fig. 9 shows drug delivery device 10 with flexible inner tube 26 rotated so that deliveiy receptacle 15 is in its delivery position and communicates with delivery outlet 24 of delivery housing 23. In this configuration, gravity causes the unit dose of therapeutic agent 13 to fall out of delivery receptacle 15 and into the mouth of the patient (not shown). The rotation of flexible inner tube 26 so that delivery receptacle 15 moves from a shut position to its delivery position, may be caused, for example by actuation of second actuator 37.

After administering the unit dose into the patient's mouth, delivery unit 14 may be moved back into its closed position, and lever 19 of actuator 18 may be moved back into its non-actuated position as shown in Fig. 4. As lever 19 returns to its non-actuated position, metering unit 16 returns to its loading position and dose receptacle is filled again with therapeutic agent 13. In addition, as lever 19 returns to its non-actuated position, delivery receptacle 15 moves into its waste position and in communication with waste outlet 25 of delivery housing 23 (as shown in Fig. 1). In the case that a patient actuates actuator 18, but, for some reason does not administer the unit dose from delivery receptacle 15 to his or her mouth, the unit dose will then fall into waste container 21 when the unit is closed. This feature helps to prevent a unit dose from remaining in an unprotected area of delivery receptacle 15 and, for example, deteriorating or becoming contaminated over time.

A subsequent actuation of actuator 18 causes a second unit dose of therapeutic agent 13 to be metered by metering device 16 and moved to delivery receptacle 15 in the same manner as previously described. Optionally, a dose counter 36 (shown in Figs. 1 and 2) may be disposed within the housing and in operable connection with actuator 18 or with metering unit 16 to count the number of unit doses that have been dispensed by the drug delivery device over time.

The present invention has been, thus far, described herein with reference to a first specific embodiment thereof. Figs. 10-24 illustrate additional embodiments incorporating variations of the first embodiment.

Referring to Fig. 10a, drug delivery device 1010a has lever handle 1001 la, while in Fig. 10b, drug delivery device 1010b includes lever handle 1001b in communication with slot 1004. The lever 19 of the embodiment of Fig. 1 is relatively long, and therefore can be subject to breakage from improper use or mishandling (for example, dropping) of the drug delivery device. The design of lever handles 1001a and 1001b shown in Figs. 10a and 10b provides protection against breakage to a lever and linkage that may be used to actuate the device.

Figs. 1 la and 1 lb show an embodiment of a drug delivery device 1110 having pivotably mounted delivery unit 114 and oppositely pivotably mounted delivery cover 1 127. Figs 12a and 12b show an embodiment of drug delivery device 1210 having rolling cover 1227, which protects delivery unit 1214 in the closed position. Rolling cover 1227 can be rolled around device 1210 to expose and allow delivery unit 1214 to be moved to an extended position.

Fig. 13 shows cover 1327 of drug delivery device 1310, which can be pivoted open to expose delivery unit 1314 and lever 1319. Cover 1327 may be lockable in an open position to provide a handle of device 1310 for the patient's use as he or she actuates lever 1319. Fig. 14 shows a similar device 1410, in which cover 1427 is made of two portions pivotable with respect to one another. In this embodiment, cover 1427 may be pivoted into an open position and folded together. Cover 1427 may also lock in an open position similar to the device of Fig. 13 to provide a handle for device 1410, as lever 1419 is actuated by a patient.

Fig. 15 shows device 1510 having cover 1527 pivotably mounted at hinge point 1528. Hinge point 1528 is also slidable along device 1510 (such as by being mounted within a slot in device 1510), so that cover 1527 may be pivoted open, and then slid along device 1510 to rest against the device. It may be useful to connect hinge point 1528 to an actuator, for example, so that the sliding of cover 1527 causes a unit dose to be metered and moved to a delivery receptacle. In Fig. 16, similar device 1610 includes cover 1627 pivotably mounted to the device at hinge point 1628. Hinge point 1628 is also slidably mounted to device 1610 so that cover 1627 may be first slid to an initially open position and then pivoted to rest against device 1610.

Figs. 17a, 17b, and 17c show device 1710 having cover 1727 slidably mounted to device 1710 (Fig. 17a). hi Fig. 17b, cover 1727 is shown in its open position and delivery unit 1714 is shown in an extended position. As shown in Fig. 17 c, depressing actuator 1718 may cause metering unit 1716 to move from a loading position in which dose receptacle is in communication with reservoir 1712, to an unloading position, in which dose receptacle 1716 is in communication with delivery receptacle 1715. As dose receptacle moves from the loading to the unloading position, it meters a unit dose of therapeutic agent 1713, which drops into delivery receptacle 1715 when it reaches the unloading position. Upon actuation of second actuator 1737 catapult mechanism 1701 causes the unit dose of therapeutic agent 1713 to be catapulted through delivery outlet 1724 of delivery unit 1714 and into the mouth of a patient (not shown).

Figs 18a, 18b and 18c show a device 1810 having sliding cover 1827. When cover 1827 is slid down, deliveiy unit 1814 may be moved to an extended position. Upon actuation of a first actuator 1818, metering unit 1817 rotates so as to cause dose receptacle 1816 to meter a unit dose of therapeutic agent 1813 and move the unit dose to delivery receptacle 1815. Upon actuation of a second actuator (not shown) the unit dose is propelled through delivery outlet 1824 of delivery unit 1814 and into the mouth of a patient (not shown). The unit dose may be propelled in one of numerous known ways, which are not illustrated in detail in Fig. 18c. Figs. 19a and 19b show device 1910. Actuation of actuator 1918 causes metering unit 1916 to meter a unit dose of therapeutic agent 1913 from reservoir 1912 and to move the unit dose to delivery receptacle 191 . Repeated actuation of second actuator 1937 causes fan 1901 to rotate, which causes a movement of air to move the unit dose of therapeutic agent 1913 from delivery receptacle 1915 through delivery outlet 1924 of delivery unit 1914 and into the mouth of a patient (not shown).

Figs. 20a - 20c show drug delivery device 2010 having cover 2027. Rotating cover 2027 around device 2010 causes an actuation of button 2001, which causes delivery unit 2014 to move to an extended position and causes device 2010 to expand. A unit dose may be metered from a reservoir and deposited in a delivery receptacle (not shown) in much the same way as previously described. A squeezing of device 2010 by a patient may cause the unit dose to move (as a result of a movement of air) from the delivery receptacle, though delivery unit 2014 and into the mouth of a patient (not shown).

The present invention has been described herein with reference to specific exemplary embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention as set forth in the claims that follow. The specification and drawings are accordingly to be regarded in an illustrative manner rather than a restrictive sense. A person of skill in the art will, of course, appreciate many ways of implementing the present invention, in addition to the embodiments described in Figs. 1-20.

Claims

WHAT IS CLAIMED IS:

1. A drug delivery device for administering a multiparticulate therapeutic agent into an oral cavity of a human patient for gastrointestinal deposition, the device comprising: a housing defining a reservoir capable of containing multiple doses of the therapeutic agent; a deliveiy unit defining a delivery receptacle, the delivery unit moveable between a closed position and an extended position, the delivery unit capable of delivering a unit dose of the therapeutic agent into the oral cavity when the delivery unit is in the extended position; a metering unit defining a dose receptacle, the metering unit moveable between a loading position, in which the dose receptacle communicates with the reservoir, and an unloading position, in which the dose receptacle communicates with the deliveiy receptacle when the delivery unit is in the closed position; and an actuator, wherein the actuator, upon actuation, is capable of causing the metering unit to move from the loading to the unloading position so as to meter the unit dose and move the unit dose from the reservoir to the delivery receptacle, the actuator configured so as to prevent the delivery unit from being moved from the closed position until after the metering unit has moved from the loading to the unloading position.

2. The drug delivery device as recited in claim 1 wherein the multiparticulate therapeutic agent includes drug particles having a mean diameter of greater than 10 μm and less than 1 mm.

3. The drug delivery device as recited in claim 1 wherein the delivery receptacle is above the metering unit when the delivery unit is in the extended position.

4. The drug delivery device as recited in claim 1 wherein the delivery unit is pivotably mounted to the housing.

5. The drug delivery device as recited in claim 1 wherein the delivery receptacle is capable of delivering the unit dose using a movement of air within the delivery receptacle.

6. The drug delivery device as recited in claim 5 wherein the delivery unit further defines an outlet passage having a funnel shape so as to cause at least one of an acceleration and a deceleration of drug particles of the multiparticulate therapeutic agent during a delivery of the unit dose to the oral cavity.

7. The drug delivery device as recited in claim 1 wherein the actuator includes a lever and a linkage between the lever and the metering unit, wherein the lever is configured so as to prevent the delivery unit from moving from the closed position until after the metering unit has moved from the loading to the unloading position.

8. The drug delivery device as recited in claim 1 further comprising a waste container defining an opening, wherein the delivery receptacle is capable of communicating with the opening of the waste container when the delivery unit is in the closed position.

9. The drug deliveiy device as recited in claim 8 wherein the delivery unit includes a delivery housing defining a delivery outlet and a waste outlet and further includes a flexible inner tube rotatable about an axis within the delivery unit, wherein a rotation of the flexible inner tube effects a movement of the delivery receptacle between a delivery position, in which the delivery receptacle communicates with the delivery outlet, a waste position, in which the delivery receptacle communicates with the waste outlet, and a shut position, in which the delivery receptacle does not communicate with either the delivery or waste outlets.

10. The drug delivery device as recited in claim 9 further comprising a cover removably disposed on the housing and capable of covering at least one of the deliveiy outlet and the waste outlet of the delivery unit when the delivery unit is in the closed position.

11. The drug delivery device as recited in claim 1 wherein the actuator is capable of covering at least one of the delivery outlet and the waste outlet of the delivery unit when the delivery unit is in the closed position.

12. The drug deliveiy device as recited in claim 1 wherein the metering unit includes a drum-shaped body defining the dose receptacle, the body rotatably disposed within a sleeve having a loading opening and an unloading opening, wherein the dose receptacle communicates with the loading opening when the metering unit is in the loading position and wherein the dose receptacle communicates with the unloading receptacle when the metering unit is in the unloading position.

13. The drug delivery device as recited in claim 12 wherein the reservoir defines, at its lower end, an exit opening communicating with the loading opening so that a rotation of the body within the sleeve is capable of metering a unit dose of the therapeutic agent from the multiple doses of the therapeutic agent in the reservoir.

14. The drug deliveiy device as recited in claim 13 wherein the housing further defines an intermediate passage communicating with the unloading opening of the sleeve so as to provide communication between the dose receptacle and the delivery receptacle.

15. The drug delivery device as recited in claim 1 wherein the delivery unit is capable of delivering the unit dose to a tongue of the oral cavity when the delivery unit is in the extended position.

16. The drug deliveiy device as recited in claim 1 wherein the actuator is further capable of effecting delivery of the unit dose from the delivery unit to the oral cavity.

17. The drug delivery device as recited in claim 1 wherein the actuator is further capable of moving the metering unit from the unloading position back again to the loading position.

18. The drug delivery device as recited in claim 1 wherein the actuator, upon a subsequent actuation, is capable of causing the metering unit to move from the loading to the unloading position so as to meter a second unit dose and move the second unit dose from the reservoir to the delivery receptacle.

19. The drug delivery device as recited in claim 18 further comprising a counter capable of counting a number of unit doses moved from the reservoir.

20. The drug delivery device as recited in claim 1 further comprising a second actuator capable of propelling the unit dose from the delivery unit to the oral cavity.

21. The drug delivery device as recited in claim 20 wherein the second actuator is capable of propelling the unit dose using at least one of forced air, a catapult mechanism, and gravity.

22. A method for administering a multiparticulate therapeutic agent into an oral cavity of a human patient for gastrointestinal deposition, the method comprising: using an actuator to move a metering unit defining a dose receptacle from a loading position, in which the dose receptacle communicates with a reservoir containing multiple doses of the therapeutic agent, to an unloading position, in which the dose receptacle communicates with a delivery receptacle of a delivery unit, the moving of the metering unit from the loading position to the unloading position effecting a metering of the unit dose and moving of the unit dose from the reservoir to the delivery receptacle; moving the delivery unit from a closed position to an extended position after the actuating of the actuator; and

• delivering the unit dose from the delivery unit into the oral cavity.

23. The method as recited in claim 22 wherein the unit dose includes drug particles having a mean diameter of greater than 10 μm and less than 1 nun.

24. The method as recited in claim 22 wherein in the opening of the delivery unit includes moving the deliveiy unit so that the delivering receptacle is above the metering unit when delivering the unit dose.

25. The method as recited in claim 22 wherein the opening of the delivery unit includes pivoting the delivery unit on the housing.

26. The method as recited in claim 22 wherein the delivering of the unit dose is performed using a movement of air within the delivery receptacle.

27. The method as recited in claim 26 wherein the delivering of the unit dose includes at least one of accelerating and decelerating drug particles of the unit dose using a funnel shape defined by an outlet passage of the delivery unit.

28. The method as recited in claim 22 further comprising moving the delivery unit back to a closed position after the delivering of the unit dose so as to enable the delivery receptacle to communicate with a waste container.

29. The method as recited in claim 28 wherein the delivery unit includes a delivery housing defining a delivery outlet and a waste outlet and further includes a flexible inner tube rotatable about an axis defined by the flexible inner tube within the delivery unit, and the method further comprises rotating the flexible inner tube so as to effect a movement of the delivery receptacle between a delivery position, in which the delivery receptacle communicates with the delivery outlet, a waste position, in which the delivery receptacle communicates with the waste outlet, and a shut position, in which the delivery receptacle does not communicate with either the delivery or waste outlets.

30. The method as recited in claim 22 further comprising covering at least one of the delivery outlet and the waste outlet of the delivery unit using a cover when the delivery unit is in the closed position.

31. The method as recited in claim 22 further comprising covering at least one of the delivery outlet and the waste outlet of the delivery unit using the actuator when the delivery unit is in the closed position.

32. The method as recited in claim 22 wherein the delivering of the unit dose is performed so as to deliver the unit dose to a tongue of the oral cavity when the delivery unit is in the extended position.

33. The method as recited in claim 22 wherein the delivering of the unit dose is performed using the actuator.

34. The method as recited in claim 22 further comprising moving the metering unit from the unloading position back again to the loading position.

35. The method as recited in claim 22 further comprising using a subsequent actuation of the actuator to cause the metering unit to move from the loading to the unloading position so as to effect a metering of a second unit dose and a moving of the second unit dose from the reservoir to the delivery receptacle.

36. The method as recited in claim 22 further comprising counting a number of unit doses moved from the reservoir using a counter.

37. The method as recited in claim 22 wherein the delivery of the unit dose is performed using a second actuator so as to propel the unit dose from the delivery unit to the oral cavity.

38. The method as recited in claim 37 wherein the delivery is performed using at least one of forced air, a catapult mechanism, and gravity.