Intranasal Cartridge Devices

• US 20080177246A1
• Filed: 01/09/2008
• Published: 07/24/2008
• Est. Priority Date: 01/09/2007
• Status: Active Grant

• Current Assignee: Mystic Pharmaceuticals Inc.
• Original Assignee: First City Tower
• Inventors: Brandenburg, Allen, Nelson, Jeffrey, Sullivan, Timothy R.
• Granted Patent: US 8,377,009 B2
• Time in Patent Office: Days
• US Class Current: 604/520
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 11/007 Syringe-type or piston-type sprayers or atomisers
• CPC Class Codes: A61M 11/06 of the injector type
• CPC Class Codes: A61M 15/0003 with means for dispensing more than one drug
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/0031 by bursting or breaking the package, i.e. without cutting or piercing
• CPC Class Codes: A61M 15/0036 hollow piercing means
• CPC Class Codes: A61M 15/004 with fixed piercing or cutting means
• CPC Class Codes: A61M 15/0051 the dosages being arranged on a tape, e.g. strips
• CPC Class Codes: A61M 15/0061 using pre-packed dosages having an insert inside
• CPC Class Codes: A61M 15/06 Inhaling appliances shaped like cigars, cigarettes or pipes
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 2202/0468 non-physiological
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/073 Syringe, piston type
• CPC Class Codes: A61M 2205/273 preventing reuse, e.g. of disposables
• CPC Class Codes: A61M 2205/276 preventing unwanted use
• CPC Class Codes: A61M 2205/583 by visual feedback
• CPC Class Codes: A61M 2205/584 having a color code
• CPC Class Codes: A61M 2205/6081 Colour codes
• CPC Class Codes: A61M 2206/16 : Rotating swirling helical flow, e.g. by tangential inflows
• CPC Class Codes: A61M 5/2425 : by compression of deformable ampoule or carpule wall
• CPC Class Codes: A61M 5/30 : Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
• CPC Class Codes: B05B 11/0035 : Pen-like sprayers
• CPC Class Codes: B05B 11/0081 : and for mixing the components in a common container as a mixture ready for use before discharging the latter
• CPC Class Codes: B05B 11/0083 : one of the components being in powder form
• CPC Class Codes: B05B 11/02 : Membranes or pistons acting on the contents inside the container, e.g. follower pistons
• CPC Class Codes: B05B 11/048 : characterised by the container, e.g. this latter being surrounded by an enclosure, or the means for deforming it B05B11/041, B05B11/046 take precedence
• CPC Class Codes: B05B 11/062 : designed for spraying particulate material
• CPC Class Codes: B05B 11/1056 : comprising rotatable or articulated levers B05B11/1053 takes precedence; lever actuated piston pumps B05B11/1009; lever actuated pumps with deformable chamber B05B11/1029
• CPC Class Codes: B05B 11/1057 : Triggers, i.e. actuation means consisting of a single lever having one end rotating or pivoting around an axis or a hinge fixedly attached to the container, and another end directly actuated by the user

Abstract

Intranasal delivery devices include dosage forms containing medical compositions for use in the intranasal devices, and methods of delivering medical compositions to the nasal mucosa of users. The devices dispense a predetermined quantity of fluid into the nasal passage of a user, in which the predetermined quantity of fluid is contained in, or produced in a dosage form or blister that is crushed by a plunger with sufficient force to drive the dosage form against a piercing mechanism, piercing the dosage form and forcing the liquid contents from the dosage form and through a delivery channel into a spray to be directed into the nasal passage of a user. The plunger is connected to a trigger device by a linkage that confers a mechanical advantage to the trigger mechanism.

Claims

1. A device for dispensing a predetermined quantity of fluid into the nasal passage of a user, said device comprising:

a body comprising a nozzle end designed for insertion into the nostril of a user;

a user operated trigger device;

a discharge nozzle;

an actuator in contact with the trigger device;

a plunger connected to the actuator;

a dosage form comprising a piercable membrane and containing the fluid; and

a piercing mechanism;

wherein operating the trigger causes the piercing mechanism to penetrate the dosage form and discharge the fluid through the discharge channel;

and further wherein the actuator modifies a mechanical force applied to the trigger device to the plunger.

2. The device of claim 1, wherein the actuator provides a mechanical advantage from the trigger device to the plunger.

3. The device of claim 1, wherein the actuator provides a mechanical disadvantage from the trigger device to the plunger.

4. The device of claim 1, wherein the actuator provides a combination of a mechanical advantage and a mechanical disadvantage from the trigger device to the plunger.

5. The device as described in claim 1, wherein a mechanical advantage is provided by a toggle mechanism actuator.

6. The device as described in claim 1, comprising:

an activation knob that is rotatable from a first position to a second position;

wherein the actuator is further defined as a toggle mechanism and wherein the activation knob is connected to the actuator such that when the activation knob is rotated from the first position to the second position, the toggle mechanism is rotated from an inactive first position to an activated position;

and wherein rotation of the toggle mechanism to the second position pushes the trigger device into an activated position.

7. The device as described in claim 6, wherein the actuator is a bar joined at one end to the activation knob in a flexible joint, joined to the piston at the opposite end in a flexible joint and forming approximately a 90°

central angle at the center point of the bar, wherein the center point is a flexible point.

8. The device as described in claim 7, wherein the trigger device is a button and wherein in the inactive position, the 90°

angle of the toggle is disposed substantially perpendicular to the direction of motion of the button, and in the activated position, the button is in contact with the apex of the central angle of the toggle.

9. The device as described in claim 7, wherein the activation knob, toggle mechanism and plunger are made as a single piece.

10. The device as described in claim 7, wherein the toggle comprises two bars, joined at the center with a hinge pin.

11. The device as described in claim 1, wherein a mechanical advantage is provided by a pivoting linkage actuator.

12. The device as described in claim 11, wherein the trigger device comprises a pivot mechanism comprising a pivot arm connected to the body by a pivot point and forming a pivot ram in contact with the plunger, wherein the pivot arm is pivotable about the pivot point from a ready position to a fired position, and further wherein pivoting the pivot arm from the ready position to the fired position causes the pivot ram to drive the plunger into the dosage form.

13. The device as described in claim 11, wherein the body comprises a stationary grip arm, wherein in the ready position the pivot arm is separated from the grip arm by a gap and when the pivot arm is in the fired position, the pivot arm is adjacent or contacting the grip arm.

14. The device as described in claim 11, wherein the design of the device incorporates an alignment guide for intranasal drug delivery, wherein when the device is held in the hand of a user such that the pivot arm is held by one or more fingers and the grip arm is held by the opposing thumb such that squeezing the pivot arm and grip arm together fires the device, placing the discharge nozzle into a nostril of the user and the gripping thumb in the depression in the chin under the lower lip provides for the correct alignment.

15. The device as described in claim 1, wherein a mechanical advantage is provided by a lever device actuator.

16. The device as described in claim 15, wherein the lever device is a lever arm and a linkage is connected to the lever arm by a slidable hinge and pin connection, wherein the lever arm is moveable from a storage position in which the lever arm is folded against the body, to a ready position in which the lever arm is raised from the body and connected to the body by a flexible connection, to a fired position in which the lever arm is folded against the body;

and further wherein the lever arm comprises a notch position such that when the lever arm is raised from the storage position to the ready position, the linkage slides along the lever arm in a forward direction until the end of the linkage engages the notch and when the linkage is engaged in the notch, the linkage is prevented from sliding along the lever arm in the rearward direction;

wherein when the lever arm is moved to the fired position, the notch forces the linkage against the plunger.

17. The device as described in claim 15, further comprising a bite arm extendable from the body, in a position such that when the discharge nozzle is placed in a nostril of a user and the bite arm is held in the teeth of the user, the device is positioned to control the direction of the discharge into the nasal passage of a user during use.

18. The device as described in claim 1, wherein a mechanical advantage is provided by an angled cam mechanism in which the device comprises:

one or more angled cams on the actuator wherein the cam comprises a forward face and a rearward face, each forming an angle with the plane of the actuator,

one or more angled cams on the trigger device, wherein the trigger cam comprises a forward face and a rearward face, each disposed at an angle relative to the plane of the actuator,

wherein the respective cams are disposed such that when a face of the actuator cam contacts a face of the trigger cam, horizontal motion of the actuator is translated to vertical motion of the trigger device, or vertical motion of the trigger device is translated to horizontal motion of the actuator.

19. The device as described in claim 18, comprising:

a body;

an activation pin extending through an opening in the body;

a sliding member contained within the body and connected to the activation pin, wherein the sliding member comprises one or more angled cam members;

a firing button comprising a bottom surface forming an angled cam positioned to interact with the one or more angled cams on the sliding member;

a plunger end connected to the sliding member; and

a chamber containing the piercable dosage form;

wherein the sliding member is slideable from a storage position to a ready position to a dispensing position;

wherein, when the sliding member is in the storage position, moving the activation pin moves the sliding member from the storage position to the ready position, and causes the sliding member to move toward the nozzle end, positioning the plunger end adjacent the chamber, and forcing a first face of the sliding member cam against an opposing first face of the angled cam on the button, forcing the button into a raised position, and positioning a second face of the angled cam on the sliding member adjacent a second face on the angled cam on the button; and

wherein, when the sliding member is in the ready position, pushing the firing button into the body forces the second face of the angled cam on the button to slide relative to the second face of the cam on the sliding member, forcing the plunger end into the chamber with a mechanical advantage relative to the force applied to the button, crushing the dosage form against the piercing mechanism and dispensing the contents of the dosage form.

20. The device as described in claim 19, wherein the device is configured to sequentially dispense two doses, and wherein the device comprises an elongated body having a first end and an opposing second end and wherein each end comprises:

a nozzle end designed for insertion into the nostril;

a discharge nozzle;

a dosage form comprising a piercable membrane and containing the fluid; and

a piercing mechanism;

and wherein the actuator comprises a plunger on each end thereof effective to sequentially dispense the contents of the piercable dosage forms from the first and second ends of the device.

21. The device as described in claim 1, comprising a latch that locks the dispensing mechanism upon discharge.

22. The device as described in claim 1, wherein the fluid comprises a medical composition in liquid form.

23. The device as described in claim 1, wherein the fluid comprises a medical composition in powdered form.

24. The device as described in claim 1, wherein the piercing mechanism is contained in the nozzle end of the body and is external to the dosage form.

25. The device as described in claim 24, wherein the piercing mechanism comprises:

a piercing point disposed adjacent the piercable membrane of the dosage form; and

a tube providing fluid communication from the piercing point to the discharge nozzle.

26. The device as described in claim 1, wherein the piercing mechanism comprises a piercing body, wherein the outer dimensions of the piercing body closely fit in the inner dimensions of the dosage form such that when the piercing body pierces the dosage form and discharges the fluid during use, the piercing body displaces substantially the entire internal volume of the dosage form.

27. The device as described in claim 1, wherein the piercing mechanism is contained in the dosage form.

28. The device as described in claim 27, wherein the piercing mechanism comprises:

an internal channel;

one or more inlet openings arranged to force one or more bends as the fluid flows into the internal channel;

a discharge outlet; and

features on the internal surface to control the spray pattern and droplet size of a fluid forced to flow through the nozzle.

29. The device as described in claim 28, wherein the features on the internal surface of the piercing mechanism comprise steps, flutes, ribs, or a combination thereof.

30. The device as described in claim 1, wherein the body of the device comprises one or more detent features to restrain the motion of the piston until a predetermined force is applied to the piston.

49. The device of claim 21, wherein the locking mechanism comprises tabs that lock the push button in the depressed position after dispensing the fluid.

50. The device of claim 21, wherein the locking mechanism comprises tabs that lock the piston in the forward position after dispensing the fluid.

51. The device of claim 1, comprising a toggle actuator, wherein the toggle actuator is broken or becomes separated by the push button after dispensing the fluid.

52. The device of claim 1, comprising a toggle actuator, wherein the actuator comprises a latch that engages a similar feature in the body to lock the toggle in the fired position after dispensing the fluid.

53. The device of claim 1, wherein the body is sealed against opening the body without destroying the device.

61. A method of controlling the direction of discharge into the nasal passage from an intranasal device of claim 1, comprising holding the device in one hand, placing the nozzle outlet into a nostril, and placing the nail side of the thumb of the hand holding the device against the chin in the recess below the lower lip.

31. A device for dispensing a predetermined quantity of fluid into the nasal passage of a user, said device comprising:

a user operated trigger device;

an actuator in contact with the trigger device;

a plunger connected to the actuator;

an dosage form containing the fluid;

a piercing mechanism;

a discharge nozzle; and

a bite arm positioned to control the direction of the discharge into the nasal passage of a user during use;

wherein operating the trigger causes the piercing mechanism to penetrate the dosage form and discharge the fluid through the discharge channel;

and further wherein the actuator provides a mechanical advantage or a mechanical disadvantage to the discharge process.

32. A device for dispensing a predetermined quantity of fluid into the nasal passage of a user, said device comprising:

a body;

a user operated trigger device;

an actuator in contact with the trigger device;

a plunger connected to the actuator;

an dosage form comprising a piercable membrane and containing the fluid; and

a piercing mechanism;

wherein operating the trigger causes the piercing mechanism to penetrate the dosage form and discharge the fluid through the discharge channel;

and further wherein the actuator provides a mechanical advantage or a mechanical disadvantage to the discharge process.

33. A device for dispensing a predetermined quantity of fluid into the nasal passage of a user, said device comprising:

a body;

a user operated trigger device;

an actuator in contact with the trigger device;

a plunger connected to the actuator; and

a removable tip comprising;

a discharge nozzle;

one or more dosage forms comprising a piercable membrane, wherein the one or more dosage forms contain a piercing mechanism and a predetermined quantity of fluid;

wherein the tip fits onto the body to place at least one dosage form adjacent the plunger;

wherein operating the trigger causes the piercing mechanism to penetrate the dosage form and discharge the fluid through the discharge nozzle;

and further wherein the actuator provides a mechanical advantage or a mechanical disadvantage to the discharge process.

34. The device as described in claim 33, further comprising a marker device disposed to leave a detectable mark on a user of the device during use.

35. The device as described in claim 34, wherein the marker is an ink pad.

36. The device as described in claim 33, wherein the tip is connected to the body with a bayonet fitting.

37. A device for dispensing a predetermined quantity of fluid in two separate discharges into nasal passages of a user, said device comprising:

a body;

a user operated trigger device;

an actuator in contact with the trigger device;

a discharge nozzle;

a plunger connected to the actuator wherein operating the trigger causes the plunger to crush the dosage form against the piercing mechanism to penetrate the dosage form and discharge the fluid through the discharge nozzle; and

a cylinder containing the plunger and providing a path for the plunger to contact and crush the dosage form;

wherein the discharge nozzle is rotatable from at least a first position to a second position, such that when the discharge nozzle is in the first position, a stop is positioned in the cylinder so that when the trigger is operated during use, the plunger is stopped after partial emptying of the dosage form, and when the discharge nozzle is in the second position, the stop is moved to allow the plunger to discharge substantially the entire contents of the dosage form when the trigger is operated during use;

and further wherein the actuator provides a mechanical advantage to the discharge process.

38. The device as described in claim 37, further comprising an alignment mark on the body and at least two position indicators on the rotatable nozzle, such that aligning a first position indicator with the alignment mark places the stop in the first position allowing partial discharge or the fluid from the dosage form, and aligning a second position indicator with the alignment mark places the stop in the second position allowing substantially complete discharge of the fluid from the dosage form.

39. The device as described in claim 37, wherein the rotatable nozzle comprises a shoulder and one or more channels, and wherein the plunger comprises one or more tabs such that when the rotatable nozzle is in the first position, the shoulder blocks the stroke of the plunger, and when the rotatable nozzle is in the second position, the tabs on the plunger are aligned with channels in the nozzle and the plunger path is unblocked.

40. A piercing nozzle for dispensing fluid from an dosage form in a controlled spray pattern and droplet size, the nozzle comprising a substantially elongate member with an inlet end and a discharge end, comprising:

an internal channel connecting the inlet end and the discharge end in fluid communication;

one or more inlet openings in the inlet end;

a discharge opening in the discharge end, and;

features on the internal channel surface to control the spray pattern and droplet size of a fluid forced through the nozzle.

41. The piercing nozzle as described in claim 40, wherein the one or more inlet ports provide a fluid path the into the internal channel, and wherein the fluid path includes one or more turns.

42. The piercing nozzle as described in claim 40, wherein the one or more inlet ports are arranged to produce a vortex in the fluid as it is forced through the nozzle.

43. The piercing nozzle as described in claim 40, wherein the features on the internal channel surface comprise steps, flutes, ribs, or a combination thereof.

44. The piercing nozzle as described in claim 40, comprising a piercing tip on the discharge opening.

45. The piercing nozzle as described in claim 40, comprising a piercing tip on the inlet end.

46. An dosage form containing the piercing nozzle of claim 40 and a medical composition.

47. An internally pierced dosage form comprising:

a substantially dome shaped, flexible blister;

a substantially round pierceable surface sealed to the base of the dome-shaped blister; and

an internal chamber;

wherein the internal chamber contains a piercing nozzle and a medical composition;

and wherein the piercing nozzle comprises;

an internal channel comprising features on the internal surface to control the spray pattern and droplet size of a fluid forced to flow through the nozzle;

one or more inlet openings providing a fluid path from the internal chamber of the dome shaped blister into the internal channel of the piercing nozzle; and

a discharge opening, wherein the internal channel provides fluid communication from the one or more inlet openings to the discharge opening;

wherein the fluid path comprises one or more bends as the fluid flows into the internal channel from the internal chamber.

48. The dosage form of claim 47, wherein the piercing nozzle comprises a base and a piercing end, and wherein the base is attached to the dome shaped blister and the piercing end is proximate the piercable surface.

54. A dosage form for administration in a liquid spray, comprising:

a blister and a backing, wherein the blister is divided into a first blister chamber and one or more second blister chambers, each separated from the first blister chamber by a secondary seal; and

a primary seal, wherein the second seal seals the circumference of the blister to the backing; and

a first liquid or powder composition within the first blister chamber and a second liquid or powder composition within at least one second blister chamber, wherein at least one of the compositions is a liquid;

wherein a secondary seal has less adhesion than the primary seal such that when a sufficient pressure is applied to a chamber, a secondary seal will release, allowing the contents of the pressurized chamber to flow into an adjoining chamber, mixing the contents of the adjoining chambers while the primary seal remains intact.

55. The dosage form as described in claim 54, wherein the first blister chamber is in the center of the blister and one or more second blister chambers partially or completely encircle the first blister chamber.

56. The dosage form as described in claim 54, wherein the chamber adjoining a pressurized chamber is made from a flexible material in an inverted shape such that flowing the contents of the pressurized chamber into the adjacent chamber causes the adjacent chamber to expand to hold the contents of both chambers.

57. The dosage form as described in claim 54, comprising an internal piercing device contained in the first blister chamber, wherein the internal piercing device comprises an internal channel comprising features on the internal surface to control the spray pattern and droplet size of a fluid forced to flow through the piercing device;

one or more inlet openings providing a fluid path from the blister chamber into the internal channel of the piercing device; and

a discharge opening, wherein the internal channel provides fluid communication from the one or more inlet openings to the discharge opening; and

wherein the fluid path comprises one or more 90°

bends as the fluid flows into the internal channel from the blister chamber.

58. A method for dispensing a pharmaceutical composition comprising two components, wherein the two components are mixed immediately prior to dispensing, the method comprising:

providing a multi chambered dosage form wherein a first component is contained in a first, crushable chamber and a second component is contained in a second, expandable chamber containing an internal piercing mechanism and discharge outlet, wherein the first and second chamber are separated by an adhesive seal;

providing a mechanical pressure to crush the crushable chamber, breaking the adhesive seal and forcing the contents of the crushable chamber into the expandable chamber; and

providing a second mechanical pressure to the expandable chamber to pierce the expandable chamber with the piercing mechanism and force the contents of the expandable chamber through the piercing mechanism and out the discharge outlet;

wherein at least one of the components is a liquid.

59. The method as described in claim 58 wherein the first and second chambers are arranged in a strip containing multiple sets of adjacent sealed chambers such that one chamber can be collapsed causing its contents to flow into the next chamber until the contents of all adjacent chambers of one set have been mixed in a single chamber of that set while the contents of all the remaining sets are kept separated.

60. The method of claim 59 wherein the strip is fed into a dispensing device comprising a first stage compression wheel or plunger to collapse the adjacent chambers of the dosage form into the primary chamber and then transport that primary chamber to a position where the contents are dispensed by the second stage plunger while leaving the remaining sets of chambers in their original separated state.