WO2020163468A1

WO2020163468A1 - Dose feedback mechanisms and assemblies for user feedback

Info

Publication number: WO2020163468A1
Application number: PCT/US2020/016779
Authority: WO
Inventors: Xian-Ming Zeng; Imran Shaikh; Abhishek Gupta
Original assignee: Lupin Inc.
Priority date: 2019-02-06
Filing date: 2020-02-05
Publication date: 2020-08-13

Abstract

The present disclosure relates to a medicament dispenser for dispensing medicament. The dispenser may be for use in dispensing medicament in a liquid, pressurized aerosol, pre-filled container and in any medicament dispenser where dose related feedback is required. Mechanisms and assemblies provide dose related feedback to the user of the medicament dispenser and the physical interfaces and attributes associated with providing such feedback. The present disclosure also relates to dose feedback assemblies that can be adapted to various form factors, various individual components and elements of the container-closure system, and/or various target user interfaces. The dispenser is suited for dispensing propellant based pressurized inhalation aerosols for oral and/or nasal delivery; aqueous or non-aqueous systems for oral and/or nasal delivery; liquid dispensers for nasal delivery, multi-dose pre-filled syringes or pens; or dispensers for intra-muscular or subcutaneous delivery and powders for pulmonary administration and tablets, capsules, pellets or agglomerates for oral administration. The dispenser may dispense a propellant based pressurized inhalation aerosol comprising one or more active pharmaceutical ingredient(s)(API) and optionally, one or more propellant, cosolvent, solubilizer, emulsifier, surfactant, salt, acid and micronized or non-micronized pharmaceutically acceptable carrier(s) and/or excipient(s), wherein the dispensing process includes a press and breathe type or breath actuated or other multi-step operation medicament dispensers.

Description

DOSE FEEDBACK MECHANISMS AND ASSEMBLIES FOR USER FEEDBACK

FIELD

[001] The present disclosure relates to a medicament dispenser for dispensing medicament. Mechanisms and assemblies provide dose related feedback to the user of the medicament dispenser and the physical interfaces and attributes associated with providing such feedback.

BACKGROUND

[002] Dose indicator or counters are useful in a wide variety of applications, and are especially important in the field of medicament dispensers where an accurate determination of the number of doses of medicament remaining in a medicament container might otherwise be difficult to obtain. Examples of such a medical dispenser includes liquid, pressurized aerosol, pre-filled containers and in any medicament dispenser where dose related feedback is required, e.g., pressurized metered-dose inhaler (pMDI), dry powder inhaler (DPI), pre-filled container, tablet/capsule dispenser, etc.

[003] Metered dose inhalers (MDI) are devices that deliver a specific amount of medication to the lungs, in the form of a short burst of aerosolized medicine that is usually self- administered by the patient via inhalation. Metered-dose inhalers include pressurized metered- dose inhalers and dry-powder inhalers. Generally, pMDIs include three major components: an aerosol canister where the formulation resides for administration to the lungs, a metering valve which is disposed in the canister and which allows a metered quantity of the formulation to be dispensed with each actuation, and an actuator which holds the canister and allows the patient to operate the device and directs the aerosol into the patient's lungs. Dry powder inhalers are devices that deliver a specific amount of medication to the lungs in the form of dry powder.

[004] Metered dose inhalers are used in order to administer an accurate dose of medicament. A more recent development is the so-called“breath actuated inhaler” which delivers a dose of drug through a mouthpiece in response to inhalation by the user. BAIs are preferred in circumstances where the coordination between user inhalation and manual depression of the aerosol canister is imperfect. For example, children have difficulty synchronizing actuation of the MDI with inhalation. Sometimes patients breathe out before inhalation is complete. [005] Unfortunately, one of the drawbacks of self-administration from conventional inhalers is that they provide no convenient way for patients to track the number of doses remaining in the canister at any given time. Thus, the illusion is created that the inhaler is still capable of providing useful doses of medicament simply because the canister contains liquid. This is potentially hazardous for the user since dosing becomes unreliable.

[006] Thus, integration of dose-counting mechanisms into MDI drug products enables users to assess how many doses remain in the obscured canister. It is recommended that manufacturers integrate a dose-counting device into new MDIs as either a numerical countdown indicating the number of remaining doses or as color-coding indicating the device should not be used.

[007] U.S. Pat. No. 5,349,945 includes a counting device for aerosol dispensers with a rotatable display means having a rack of teeth which is driven by a ratchet during the dispensing of a medicament dose. Each tooth on the rack corresponds to a single dose. However, miscounting might occur with one poor tooth. This requires all of the teeth in the rack to be perfect.

[008] U.S. Pat. No. 5,988,496 describes a device for counting doses of substance issued by a dispenser. The device includes a first count wheel and second count wheel mounted to rotate about a common axis of rotation. The first count wheel includes a drive tongue that is movable between a rest position, in which it does not cooperate with the second count wheel, and a drive position, in which it cooperates with the second count wheel to cause it to rotate about the common axis of rotation. The drive tongue is forced into position by action of a cam. Such device might possess difficulty in robust transfer and distribution of motion upon actuation.

[009] Although such devices have provided the advantage of being able to provide some measure of the number of doses of medicament dispensed from a container and/or the number of doses remaining therein, there remains room for improvement. In particular, it has proven difficult to provide dose counters that reliably“count” the release of medicament doses from containers. Moreover, there is also regulatory pressure to minimize the number of false counts. Naturally, there is a need to develop a dose feedback mechanism that is efficient and robust.

[010] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgement or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavor to which this specification relates. SUMMARY:

[Oi l] The present disclosure provides for mechanisms and assemblies for providing dose related feedback to the user of the medicament dispenser and the physical interfaces and attributes associated with providing such feedback. The dispenser may dispense medicament in a liquid, pressurized aerosol, pre-filled container, or in any medicament dispenser where dose related feedback is required. The present disclosure also relates dose feedback assemblies that can be adapted to various form factors, various individual components and elements of the container-closure system, and/or various target user interfaces. The dispenser is suited for dispensing propellant based pressurized inhalation aerosols for oral and/or nasal delivery; aqueous or non-aqueous systems for oral and/or nasal delivery; liquid dispensers for nasal delivery and powders for pulmonary administration and tablets, capsules, pellets or agglomerates for oral administration; or pre-filled syringes or pens or dispensers for intra muscular or subcutaneous delivery. The dispenser may dispense a propellant-based pressurized inhalation aerosol comprising one or more active pharmaceutical ingredient(s)(API) and optionally, one or more propellant, cosolvent, solubilizer, emulsifier, surfactant, salt, acid and micronized or non-micronized pharmaceutically acceptable carrier(s) and/or excipient(s), wherein the dispensing process includes a press and breathe-type or breath-actuated or other multi-step operation medicament dispensers. The present disclosure also relates to dry powder inhaler-type devices comprising one or more active pharmaceutical ingredient(s) and optionally, one or more micronized or non-micronized pharmaceutically acceptable carrier(s) and/or excipient(s) wherein the dispensing process includes multi-step operation medicament dispensers such as open, dispense, and close.

[012] In some embodiments, the mechanism of actuation leads to change in the number of doses (increment or decrement) and provides dose related feedback (e.g., number remaining, number consumed, and/or life-cycle of the product) to the user of the medicament dispenser.

[013] In some embodiments, the mechanism of actuation leads to change in the number of doses (increment or decrement) and also leads to the exhaustion/evacuation of the contents of the primary packaging to provide dose-related feedback (e.g., number remaining, number consumed, and/or life-cycle of the product) to the user of the medicament dispenser.

[014] In some embodiments, the dose count feedback is provided through a dose indicator assembly, wherein dose feedback mechanism includes a mechanism by which the dose-related (e.g., number remaining, number consumed, and/or life-cycle of the product) visual feedback (e.g., readout) is provided to the use. [015] In some embodiments, the dose feedback mechanism is provided through a dose indicator assembly which further comprises dose indicating means.

[016] In some embodiments, the dose feedback mechanism is provided through a dose indicator assembly including printed tape, a belt, or a scroll.

[017] In some embodiments, a‘window’ (or interface or display) provides the dose-related (e.g., number remaining, number consumed, and/or life-cycle of the product) visual feedback (e.g., readout) to the user of the medicament dispenser.

[018] In some embodiments, the dose feedback mechanism ranges from numbers‘0’ to‘200’ which are displayed through the window (or interface or display).

[019] In some embodiments, a large window (or interface or display) displays the individual digits (e.g., numerical feedback) in a vertical or horizontal orientation and provides for the dose related (e.g., number remaining, number consumed, and/or life-cycle of the product) visual feedback (e.g., read-out) to the user of the medicament dispenser.

[020] In some embodiments, the dose feedback mechanism includes the operation of a plunger coupled with a driving cam of the dose indicator assembly, transforming motion from actuation/operation of the medicament dispenser to the dose feedback mechanism of the medicament dispenser.

[021] In some embodiments, the rectilinear motion of the primary packaging of the medicament dispenser during the actuation/operation of the medicament dispenser is converted to rotational motion of the dose feedback mechanism.

[022] In some embodiments, the rectilinear motion of the mechanism for actuation/operation of the medicament dispenser is mechanically converted to rectilinear motion for the operation of the dose feedback mechanism and wherein this rectilinear motion is further converted to the rotational motion of the dose feedback mechanism of the medicament dispenser.

[023] In some embodiments, the rotational motion of the mechanism for operating/opening/actuating the medicament dispenser is mechanically converted to rectilinear motion which is further converted into the rotational motion of the dose feedback mechanism of the medicament dispenser.

[024] In some embodiments, the dose feedback mechanism is directly connected to the mechanism of operating/opening/actuating the medicament dispenser.

[025] In some embodiments, the dose feedback mechanism includes a scroll having an ascending or descending read-outs, printed or etched or embossed or colored thereon.

[026] In some embodiments, the dose feedback mechanism includes a scroll that moves synchronously and simultaneously with the movement of the primary packaging and provides read-out printed or etched or embossed or colored thereon through the window (or interface or display).

[027] In some embodiments, the dose feedback mechanism includes a scroll that moves synchronously and simultaneously with the movement of the primary packaging and with the aid of one or more wheels or shafts and provide read-out printed or etched or embossed or colored thereon through the window (or interface or display).

[028] In some embodiments, the dose feedback mechanism includes a plunger, cam, dummy wheel, driving roller, driven roller, one or more locks to prevent the reverse rotation of the dummy wheel and/or a dose indicating means for providing a dose-related visual feedback to the user of the medicament dispenser.

[029] In some embodiments, the dose feedback mechanism includes a plunger and driving cam wherein rectilinear motion of the plunger is converted in rotational motion through cam; a dummy wheel, driving roller, driven roller, one or more locks to prevent the reverse rotation of the dummy wheel and/or a dose indicating means for providing a dose related visual feedback to the user of the medicament dispenser wherein it comprises a scroll to provide a count ranging from‘O’ to‘200’; wherein the driving cam rotates the dummy wheel which further rotates the driving roller; thereby moving the scroll to provide the readout of the count.

[030] In some embodiments, a dose indicator assembly includes a mount, plunger, cam, dummy wheel, driving roller, driven roller and/or a dose indicating means for providing a dose- related visual feedback to the user of the medicament dispenser.

[031] In some embodiment, a dose indicator assembly includes a mount, plunger, cam, dummy wheel, driving roller, driven roller and/or a dose indicating means including a scroll for providing a dose-related visual feedback to the user of the medicament dispenser.

[032] In some embodiments, the dose feedback mechanism includes a plunger and cam drive mechanism that allow for an efficient and robust transfer and distribution of motion from the actuation/operation of the medicament dispenser to and within the dose feedback mechanism and allow for relative serial reduction in the unit count of doses remaining in the medicament dispenser. The dose feedback mechanism also allows for relative serial reduction of the unit count of doses remaining in the medicament dispenser. The dose feedback mechanism provides for lower friction and smooth operation.

[033] In some embodiments, the dose feedback mechanism includes a plunger and cam drive that prevent an inadvertent miss in the transfer and distribution of motion of the primary packaging within the dose indictor mechanism and prevent a false higher remaining dose count within the medicament dispenser. The dose feedback mechanism provides for lower friction and smooth operation.

[034] In some embodiments, the dose feedback mechanism provides features to prevent reverse movement of dose indicating means in the medicament dispenser.

[035] In some embodiments, the dose feedback mechanism provides features that lend its utility in a reusable dose feedback mechanism and in a separable cartridge or cassette for re use and re-loading of the medicament dispenser.

[036] In some embodiments, the dose feedback mechanism includes a mechanical dose indicating mechanism and an electronic dose indicating mechanism that operate in a synchronous, collective, tandem, and redundant manner.

[037] In some embodiments, the material of construction of the components of the dose feedback mechanism includes acrylonitrile butadiene styrene (ABS), poly carbonate/ acrylonitrile butadiene styrene terpolymer blend (PC/ABS), Polyoxymethylene (POM), nylon, stainless steel and/or silicone rubber.

[038] In some embodiments, the material of construction of the components of the dose feedback mechanism includes acrylonitrile butadiene styrene (ABS), poly carbonate/ acrylonitrile butadiene styrene terpolymer blend (PC/ABS), Polyoxymethylene (POM) and/or nylon.

[039] In some embodiments, the dose feedback mechanism also provides for complete dose lock-out and complete operation lock-out features after all doses in the medicament dispenser are dispensed and the medicament dispenser is exhausted.

BRIEF DESCRIPTION OF DRAWINGS

[040] Fig. 1 A shows an isometric view of an embodiment of the medicament dispenser.

[041] Fig. IB shows a partial-exploded isometric view of a different embodiment of the medicament dispenser.

[042] Fig. 2 shows an exploded view of the medicament dispenser shown in Fig. 1 A, showing a dose indicator assembly.

[043] Fig. 3 shows an actuator and the dose indicator assembly shown in Fig. IB assembled together.

[044] Fig. 4 shows the view of a window displaying the count.

[045] Figs. 5A, 5B and 5C show various isometric views of the actuator shown in Fig. 1 A. [046] Fig. 6 shows a sectional view showing the actuator shown in Fig. 1 A, balancer and dose indicator assembly.

[047] Fig. 7A shows a half-moon balancer.

[048] Fig. 7B shows a bar type balancer.

[049] Fig. 7C shows a disc type balancer.

[050] Fig. 8 shows an arrangement of a dose indicator assembly and a balancer.

[051] Fig. 9 shows a dose indicator assembly.

[052] Figs. 10A and 10B show an exploded view of the dose indicator assembly and its operation.

[053] Fig. 11 shows an isometric view of a mount of the dose indicator assembly.

[054] Fig. 12 shows an isometric view of a driving roller

[055] Fig. 13 shows an isometric view of a driven roller

[056] Fig. 14 shows an isometric view of a driving cam

[057] Fig. 15 shows an isometric view of a cam plunger link

[058] Figs. 16A and 16B show different isometric views of a dummy wheel.

[059] Figs. 17A and 17B show a scroll and its representation.

[060] Figs. 18-20 show the operating cycle of a dose indicator with an initial dose count of 120 doses.

DETAILED DESCRIPTION:

[061] The present disclosure provides for mechanisms and assemblies for providing dose related feedback to the user of the medicament dispenser and the physical interfaces and attributes associated with providing such feedback.

[062] A medicament dispensers, as disclosed herein, have a variety of structural configurations and can be used for dispensing liquids, powders, tablets, capsules, pellets or pucks, or mixtures thereof for nasal, pulmonary or oral administration. In particular, the medicament dispensers can be used to dispense a liquid comprising one or more active pharmaceutical ingredient(s) (API) and optionally, one or more pharmaceutically acceptable carrier(s) and/or excipient(s). The dispenser may dispense a propellant based pressurized inhalation aerosol comprising one or more active pharmaceutical ingredient(s)(API) and optionally, one or more propellant, cosolvent, solubilizer, emulsifier, surfactant, salt, acid, and micronized or non-micronized pharmaceutically acceptable carrier(s) and/or excipient(s), wherein the dispensing process includes a press-and-breathe type, breath-actuated, or other multi-step operation medicament dispensers. Further, the present disclosure relates to dispensing powdered medicament wherein the dispensing process includes a press-and-breathe type or breath-actuated or other multi-step operation medicament dispensers.

[063] One or more active pharmaceutical ingredient(s) (APIs) that can be used can be selected from analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, e.g., diltiazem; antiallergics, e.g., cromoglycate (e.g. as the sodium salt), ketotifen or nedocromil (e.g. as the sodium salt); antiinfectives e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine; antihistamines, e.g., methapyrilene; anti-inflammatories, e.g., beclomethasone (e.g. as the dipropionate ester), fluticasone (e.g. as the propionate ester), flunisolide, budesonide, rofleponide, mometasone e.g. as the furoate ester), ciclesonide, triamcinolone (e.g. as the acetonide) or 6a,9a-difluoro-l ip- hydroxy- 16a-methyl-3-oxo- 17a.-propionyloxy-androsta-l,4-diene-17P-carbothioic acid S-(2- oxo-tetrahydro-furan-3- yl) ester; antitussives, e.g., noscapine; bronchodilators, e.g., albuterol (e.g. as free base or sulphate), salmeterol (e.g. as xinafoate), ephedrine, adrenaline, fenoterol (e.g. as hydrobromide), formoterol (e.g. as fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (e.g. as acetate), reproterol (e.g. as hydrochloride), rimiterol, terbutaline (e.g. as sulphate), isoetharine, tulobuterol or 4- hydroxy - 7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)- benzothiazolone; adenosine 2a agonists, e.g. 2R,3R,4S,5R)-2-[6-Amino-2-(l S- hydroxymethyl-2-phenyl- ethylamino)-purin-9-yl]-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro- furan-3,4-diol (e.g. as maleate);. a4 integrin inhibitors e.g. (2S)-3-[4-({[4- (aminocarbonyl)-l- piperidinyl]carbonyl}oxy)phenyl]-2-[((2S-)-4-methyl-2-{[2-(2

methylphenoxy)acetyl]amino}pentanoyl)amino]propanoic acid (e.g. as free acid or potassium salt), diuretics, e.g., amiloride; anticholinergics, e.g., ipratropium (e.g. as bromide), tiotropium, atropine or oxitropium; hormones, e.g., cortisone, hydrocortisone or prednisolone; xanthines, e.g., aminophylline, choline theophyllinate, lysine theophyllinate or theophylline; therapeutic proteins and peptides, e.g., insulin or glucagon; vaccines, diagnostics, and gene therapies. It will be clear to a person skilled in the art that, where appropriate, the medicaments may be used in the form of salts, (e.g., as alkali metal or amine salts or as acid addition salts) or as esters (e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimize the activity and/or stability of the medicament

[064] The term“dose feedback mechanism” includes the mechanism by which the dose related (e.g., number remaining, number consumed, and/or life-cycle of the product) visual feedback (e.g., read-out) is provided to the user. [065] In some embodiments, the dose feedback mechanism includes the actuator, the dose indicator assembly, the balancer, and the window.

[066] An actuator houses a dose indicator assembly, the canister, bottle or medicament carrier (such as reel of blisters) containing the formulation, the balancer and the window. The actuator may contain plunger guides that allow for the plunger of the dose indicator assembly to move in a rectilinear motion during the operation/actuation of the medicament dispenser.

[067] The rectilinear motion means a straight line motion. A body is said to experience rectilinear motion if any two particles of the body travel the same distance along two parallel straight lines with uniform velocity. The rectilinear motion may constitute reciprocal motion.

[068] In some embodiments, the dose feedback mechanism comprising of the dose indicator assembly includes a mount, plunger, cam, dummy wheel, driving roller, driven roller and/or a dose indicating means for providing a dose related visual feedback to the user of the medicament dispenser.

[069] The mount holds and locates all the components of the dose indicator assembly and has one or more features such as driving roller shaft, driven roller shaft and a lock to prevent reverse rotation of the dummy wheel.

[070] The driving roller has a hollow shaft. The driving roller has spur gears. These spur gears are always in contact with dummy wheel spur gear.

[071] The driving roller shaft has driving roller guides which support the driving roller.

[072] The driven roller shaft has driven roller guides which support and guide the scroll wounded around driven roller.

[073] The plunger includes a means for engagement to the cam. It is pushed down during actuation/operation. A plunger has an arrangement to attach a spring which assists in the return movement of the plunger after actuation/operation. A is plunger configured for rectilinear motion.

[074] A“driving cam” is a rotating or sliding piece in a mechanical linkage used in transforming rectilinear motion into the rotary motion. The driving cam has driving studs. A cam plunger link, pin short and pin long connects the driving cam with plunger.

[075] A dummy wheel has radial ratchets and spur gears. The dummy wheel has slits on its surface. The slits and wheel lock prevent the reverse rotation of the dummy wheels.

[076] The term“ratchet” includes a type of gear or arrangements of teeth in such way that it allows continuous linear or rotary motion in only one direction while preventing motion in the opposite direction. [077] A dose indicating means includes a printed tape, belt or a scroll.

[078] As used herein the terms printed tape, belt or a scroll can be used interchangeably.

[079] A dose indicating means includes a scroll having ascending or descending read-outs, printed, etched, embossed or colored thereon.

[080] The primary packaging in case of MDI refers to a bottle, canister or actuator, and its components such as mouth piece cover.

[081] The balancer transfer distributes and equalizes the force of primary packaging on the linear racks. The balancer resides on top of the two linear rack of the dose indicator assembly. The rectilinear or rotational motion of the primary packaging material, (e.g., canister, bottle or cover) is transferred to the dose indicator assembly via the balancer. The balancer can have different shapes such as disc type, half moon, and/or bar type. The balancer may have one or more slot(s) for plunger. The balancer may further have a guide for guiding the movement of the balancer.

[082] In some embodiments a dose indicator assembly includes: a mount, a plunger, a driving cam, a dummy wheel, and/or a dose indicating means for providing a dose related visual feedback to the user of the medicament dispenser.

[083] In some embodiments, the dose feedback mechanism includes the dose indicator assembly which includes: a mount, a plunger, a driving cam, a dummy wheel, a driving roller, a driven roller and/or a dose indicating means which includes of a scroll for providing a dose related visual feedback to the user of the medicament dispenser.

[084] In some embodiments, the dose feedback mechanism includes of the dose indicator assembly which includes: a mount, a plunger, a driving cam, a dummy wheel, a driving roller, a driven roller and/or a dose indicating means which includes a scroll for providing a dose related visual feedback to the user of the medicament dispenser. The driving roller, dummy wheel and the driving cam may be coaxial.

[085] In some embodiments, the dose feedback mechanism includes the dose indicator assembly which includes: a mount comprising driving roller shaft, driven roller shaft and a lock; a plunger; a driving cam; a dummy wheel, a driving roller, a driven roller, a cam plunger link, a pin short, a pin long and/or a dose indicating means which includes a scroll wound around the driven roller for providing a dose related visual feedback to the user of the medicament dispenser. The driving roller, dummy wheel and the driving cam may be coaxial.

[086] In some embodiments, the dose feedback mechanism comprises of the dose indicator assembly which includes: a mount comprising driving roller shaft, driven roller shaft and a lock; a plunger; a driving cam; a dummy wheel; a driving roller; a driven roller; cam plunger link; pin short; pin long and a dose indicating means which includes a scroll wound around the driven roller for providing a dose related visual feedback to the user of the medicament dispenser. The driving roller, dummy wheel and the driving cam are coaxial. The driving roller shaft holds the driving roller and driven roller shaft holds the driven roller. The plunger and driving cam are connected by the cam plunger link, pin short and pin long.

[087] In some embodiments, the dose feedback mechanism includes of the dose indicator assembly which includes: a mount comprising driving roller shaft, driven roller shaft and a lock; a plunger; a driving cam; a dummy wheel; a driving roller; a driven roller; a cam plunger link; a pin short; a pin long and/or a dose indicating means which includes a scroll wound around the driven roller for providing a dose related visual feedback to the user of the medicament dispenser. The driving roller, dummy wheel and the driving cam are coaxial. The driving roller shaft holds the driving roller and driven roller shaft holds the driven roller. The plunger and driving cam are connected by the cam plunger link, pin short and pin long. The driving cam rotates the dummy wheel which further rotates driving roller.

[088] In some embodiments, when the primary packaging, e.g. canister or bottle are depressed to actuate/operate the medicament dispenser the motion is transferred to the plunger which moves it in a downward direction. The downward motion of the plunger is transferred to the driving cam which further converts it to the rotational motion. The driving cam have the radially placed driving studs that drive a dummy wheel which further drive the driving roller leading to advancement of scroll on the driving roller hollow shaft of the driving roller. The spring assists in the return movement of the plunger after actuation/operation. The radial ratchets of the dummy wheel together with the wheel lock prevent the reverse rotation of the dummy wheels during the return movement of the plunger. The scroll moves upon every actuation or operation. The mechanism of actuation leads to change in the number of doses (increment or decrement) and provides dose related feedback (e.g. number remaining; number consumed and/or life-cycle of the product) to the user of the medicament dispenser.

[089] When the primary packaging e.g. cover of dry powder inhaler is opened to actuate/operate the medicament dispenser the motion is transferred to the plunger which moves it in a downward direction. The downward motion of the plunger is transferred to the driving cam which further converts it to the rotational motion. The driving cam has the radially placed driving studs that drive a dummy wheel which further drive the driving roller leading to advancement of scroll on the driving roller hollow shaft of the driving roller. The spring assists in the return movement of the plunger after actuation/operation. The radial ratchets of the dummy wheel together with the wheel lock prevent the reverse rotation of the dummy wheels during the return movement of the plunger. The scroll moves upon every actuation or operation. The mechanism of actuation leads to change in the number of doses (increment or decrement) and provides dose related feedback (e.g. number remaining; number consumed and/or life- cycle of the product) to the user of the medicament dispenser.

[090] In some embodiments, the dose feedback mechanism includes of the dose indicator assembly which includes: a mount comprising a shaft, a plunger configured for rectilinear motion, a driving cam configured to convert the rectilinear motion of the plunger into rotational motion, the driving cam configured to rotate about the shaft, a dummy wheel interfacing with the driving cam, and a dose indicating means for providing a dose related visual feedback to the user of the medicament dispenser

[091] In some embodiments, the dose feedback mechanism includes: the actuator; the dose indicator assembly including a mount, a plunger, a driving cam, a dummy wheel, a driving roller, a driven roller and a dose indicating means which includes a scroll for providing a dose related visual feedback to the user of the medicament dispenser; the balancer; and/or the window for displaying the change in the number of doses (increment or decrement) and provides dose related feedback (e.g. number remaining; number consumed and/or life-cycle of the product) to the user of the medicament dispenser.

[092] In some embodiments, the dose feedback mechanism includes: the actuator; the dose indicator assembly including a mount, a plunger, a driving cam, a dummy wheel, a driving roller, a driven roller and a dose indicating means which includes of a scroll for providing a dose related visual feedback to the user of the medicament dispenser; the balancer; and/or the window for displaying the change in the number of doses (increment or decrement) and provides dose related feedback (e.g. number remaining; number consumed and/or life-cycle of the product) to the user of the medicament dispenser. The driving roller, dummy wheel and the driving cam are coaxial.

[093] In some embodiments, the dose feedback mechanism includes: the actuator; the dose indicator assembly including a mount comprising driving roller shaft, driven roller shaft and a lock; a plunger; a driving cam; a dummy wheel; a driving roller; a driven roller; a cam plunger link; a pin short; a pin long; a dose indicating means which includes a scroll for providing a dose related visual feedback to the user of the medicament dispenser; the balancer; and/or the window for displaying the change in the number of doses (increment or decrement) and provides dose related feedback (e.g. number remaining; number consumed and/or life-cycle of the product) to the user of the medicament dispenser. The driving roller, dummy wheel and the driving cam are coaxial. The driving roller shaft holds the driving roller and driven roller shaft holds the driven roller. The plunger and driving cam are connected by the cam plunger link, pin short and pin long. The driving cam rotates the dummy wheel which further rotates driving roller.

[094] The presence of the cam drive and the plunger prevents an inadvertent miss in the transfer and distribution of motion of the primary packaging within the dose feedback mechanism and prevents a false higher remaining dose count within the medicament dispenser.

[095] The presence of the cam drive and the plunger allows for an efficient and robust transfer and distribution of motion from the actuation/operation of the medicament dispenser to and within the dose feedback mechanism and allows for relative serial reduction in the unit count of doses remaining in the medicament dispenser.

[096] Figs. 1 A and IB show types of actuators 36 for metered dose inhalers having a window 48. A canister 56 or bottle 65 can be inserted in to the actuator 36.

[097] Fig. 2 shows an exploded view of the medicament dispenser showing actuator 36, dose indicator assembly 57, dose indicator assembly cover 58 and window 48.

[098] Fig. 3 shows an assembled view of actuator 36 and dose indicator assembly 57.

[099] Fig. 4 shows the view of window 48 displaying the count through the window.

[100] Figs. 5 A, 5B and 5C shows top isometric views of an actuator showing the dose indicator assembly 57, the balancer disc 43 and the window 48. The dose indicator assembly 57 provides dose count feedback ranging from numbers‘O’ to‘200’ which are displayed synchronously and simultaneously through the window 48. The actuator 36 includes an actuator plunger guide 69 that allows plunger 17 to move in a rectilinear motion through actuator plunger guide 69 during the operation/actuation of the medicament dispenser. As shown, the dose indicator may only include a single plunger 17. The balancer disc 43 includes a balancer slot for plunger 68 that is aligned with the plunger 17 and actuator plunger guide 69 on the actuator 36. The balancer disc 43 resides on top of the actuator plunger guide 69 of the actuator 36 and the dose indicator assembly 57. The rectilinear motion of the canister 56 or bottle 65 within the body of the actuator 36 is transferred to the dose indicator assembly 57 via the balancer disc 43. The operation/actuation of the medicament dispenser includes rectilinear motion of the canister 56 or bottle 65 within the body of the actuator 36 transferred to the plunger 17 on the dose indicator assembly 57 via the balancer disc 43.

[101] Fig. 6 shows a sectional view showing the actuator 36, disc type balancer 43, dose indicator assembly 57, plunger 17 and actuator plunger guide 69.

[102] Figs. 7A, 7B and 7C show different types of balancers. Fig. 7A shows half-moon type balancer 38 having balancer half-moon guide 39 and a balancer slot for plunger 66. The balancer half-moon guide 39 on the balancer half-moon 38 moves within the actuator slot for balancer 40 (see figs. 5B and 6) and provides support during the rectilinear motion of the balancer under the pressure from the canister 56 or bottle 65. Fig 7B shows bar type balancer 41 with balancer bar surface 42. Fig 7C shows balancer disk type balancer 43 having balancer slot for plunger 66. The balancer serves the functions of providing a dynamic guide for the canister 56 or bottle 65 and the transfer, distribution and equalization of the force on the plunger 17 of the dose indicator assembly 57 from the rectilinear motion of the canister 56 or bottle 65. This efficient and consistent transfer of force from the motion of the canister 56 or bottle 65 to the dose indicator assembly 57 allows for a consistent and efficient operation of the dose indicator assembly 57 and prevents an inadvertent miss in the change in dose count during the actuation/operation of the medicament dispenser.

[103] Fig. 8 shows an arrangement of dose indicator assembly 57 and disc type balancer 43. The tip of plunger 17 fits into the balancer slots for plunger 66.

[104] Fig. 9 shows a dose indicator assembly. The dose indicator assembly may only include a single drive mechanism at one end of the scroll 55, although in other embodiments, the dose indicator assembly may include additional drive mechanism(s), for example on the opposite side of the scroll 55. The figure shows the mount 1, driving roller 13, driven roller 16, plunger 17, dummy wheel 9, driving cam 19, cam plunger link 20, pin short 21, pin long 22, driven roller shaft 50, driving roller guide 51, the scroll 55 and the spring 60. As shown, the dose indicator assembly may only include a single driving cam 19 and a single dummy wheel 9. The mount 1 holds and locates all the components of the dose indicator assembly and has wheel lock 34, driving roller shaft 49, driven roller shaft 50, driving roller guide 51 and driven roller guides 54 (see fig. 11). The driving roller 13 has driving roller hollow shaft 44 and spur gears 53 (see fig. 12). The driving roller hollow shaft 44 rides on the stationery driving roller shaft 49. The driven roller 16 rides on the driven roller shaft 50 and guided by the driven roller guide. The scroll 55 is wound around the driven roller 16 and the other end is connected to the driving roller 13. The driving cam 19 has the driving stud 23 (see fig. 14). The dummy wheel 9 has the radial ratchets 24 and the spur gears 52 (see figs. 16A and 16B). The driving stud 23 of the driving cam 19 are always in contact with radial ratchets 24 of the dummy wheel 9. The driving cam 19 is connected to the plunger 17 through the cam plunger link 20, pin short 21, and pin long 22. This dose indicator set-up allows for a three digit (units) read-out and feedback on dose numbers in a medicament dispenser ranging from‘O’ to‘200’ via a printed or etched or embossed or colored scroll 55. [105] Figs. 10A and 10B show exploded views of the dose indicator assembly and its operation. The driving cam 19 converts the rectilinear motion of the plunger 17 to rotational motion. The cam plunger link 20, pin short 21 and pin long 22 connect the plunger 17 to the driving cam 19. The cam plunger link 20 also contributes towards conversion of the linear motion of the plunger 17 to the rotary motion of the dummy wheel 9. The driving cam 19 rotates about the stationary driven roller shaft 50 on the mount 1. The driven roller shaft 50 may extend from only one side of the mount 1. For example, one end of the driven roller shaft

50 may extend from the mount 1 and the driving cam 19 may rotate about the opposite end of the driven roller shaft 50. The driving stud 23 on the driving cam 19 rotate the dummy wheel 9 via the radial ratchets 24. The radial ratchets 24 allow unidirectional motion of the dummy wheel 9. The dummy wheel spur gears 52 drives the driving roller 13 via the spur gears 53 of the driving roller. The driving roller 13 driven by the dummy wheel 9 rides on the stationary driving roller shaft 49. The spur gears 53 of driving roller are in contact with the spur gears 52 of the dummy wheel 9. The driven roller 16 rotates about the stationary driven roller shaft 50 which is fixed on mount 1. The driven roller 16 is supported by the driven roller guides 54 of the driven roller shaft 50. A scroll 55 is wound around the driven roller 16. The other end of the scroll 55 is fixed on the driving roller hollow shaft 44 of the driving roller 13. During each actuation/operation of the medicament dispenser the driving roller hollow shaft 44 of the driving roller 13 rotates incrementally, thereby moving the scroll 55 over driven roller 16 to the driving roller and displaying the dose count through the window 48 on the actuator 36.

[106] Fig. 11 shows an isometric view of mount 1. The mount 1 has wheel lock 34, driving roller shaft 49, driven roller shaft 50, driving roller guide 51 and driven roller guides 54. The mount 1 provides for a stationery fixture that holds all the moving components of the dose indicator assembly 57. The driven roller 16, dummy wheel 9 and the driving cam 19 rotate about the driven roller shaft 50 on the mount 1 (see fig. 9). The driving roller shaft 49 locates the driving roller 13 via the driving roller hollow shaft 44 (see fig. 9). The driving roller guide

51 prevents lateral motion of the driving roller 13. The wheel lock 34 prevents the reverse rotation of the dummy wheel 9. The driven roller guides 54 prevent the lateral motion of the driven roller 16 and also guides the scroll 55.

[107] Fig. 12 is an isometric view of driving roller 13. The driving roller spur gears 53 and driving roller hollow shaft 44.

[108] Fig. 13 is an isometric view of driven roller 16.

[109] Fig. 14 is an isometric view of driving cam 19. The driving cam 19 has driving stud 23. [110] Fig. 15 is an isometric view of cam plunger link 20. The driving cam 19 and the plunger 17 are connected by cam plunger link 20 and pin short 21 and pin long 22.

[111] Figs. 16A and 16B show different isometric views of dummy wheel 9. The dummy wheel 9 has slits 14, radial ratchets 24 and spur gear 52.

[112] Figs. 17A and 17B show a scroll 55 and its representation.

[113] Figs. 18-20 show the operating cycle of the dose indicator with an initial dose count of 120 doses. The spring 60 loaded plunger 17 provides a rectilinear motion. The plunger 17 is driven by the motion of the canister 56 or bottle 65 through the actuator 36 either by the press and breathe operation by the user or by breath actuated mechanism of the medicament dispenser. The operation/actuation of the medicament dispenser involves the rectilinear motion of the canister 56 or bottle 65 within the body of the actuator 36 which is transferred to the plunger 17. The plunger 17 allows for an efficient and robust transfer and distribution of motion from the actuation/opening of the medicament dispenser to and within the dose indicator assembly 57 and allows for relative serial reduction in the unit count of doses remaining in the medicament dispenser. The spring 60 assists in the return movement of the plunger 17 after actuation/operation. The cam plunger link 20, pin short 21 and pin long 22 connects the plunger 17 to the driving cam 19. The plunger 17 rotates the driving cam 19 via the plunger link 20 in the clockwise and counter clockwise direction as the plunger 17 moves in the reciprocal motion i.e up and down in the actuator. The driving cam 19 converts the rectilinear motion of the plunger 17 to rotational motion. The cam plunger link 20 also contributes towards conversion of the rectilinear motion of the plunger 17 to the rotary motion of the dummy wheel 9. The driving cam 19 includes driving stud 23 that rotates the dummy wheel 9 via the radial ratchets 24. The radial ratchets 24 on the dummy wheel 9 prevent the bi-directional motion of the dummy wheel 9. The dummy wheel 9 drives the driving roller 13 in the opposite direction. The driving roller 13 and the driven roller 16 rotate about the driving roller shaft 49 and the driven roller shaft 50, respectively. Initially the scroll 55 is wound around the driven roller 16 of the driving roller 13 and the other end of the scroll 55 is fixed on the driving roller hollow shaft 44. The rotation of the dummy wheel 9 causes the scroll 55 to advance over the driving roller hollow shaft 44 from the driven roller 16 (refer fig. 19). When the canister 56 or bottle 65 is not depressed and returns back to its original state, the spring 60 un-compresses and moves the plunger 17 vertically to its original state (see fig. 20). The wheel lock 34, slits 14 and radial ratchets 24 prevents the reverse rotation of the dummy wheel 9. At this stage there is no movement of the dummy wheel 9 and hence the scroll 55. The scroll 55 moves upon each actuation/operation leads to change in the number of doses providing life-cycle of the product to the user of the medicament dispenser.

[114] It is intended that the scope of the present disclosure should not be limited by any particular embodiment described herein. While various embodiments have been described above, it should be noted that they have been presented by way of example only, and not limitation. Numerous changes to the disclosed embodiments can be made in accordance with the disclosure herein without departing from the spirit or scope of the invention.

Claims

Claims:

1. A dose indicator assembly comprising,

a mount comprising a shaft;

a plunger configured for rectilinear motion;

a driving cam configured to convert the rectilinear motion of the plunger into rotational motion, the driving cam configured to rotate about the shaft;

a dummy wheel interfacing with the driving cam; and

a dose indicating means for providing a dose related visual feedback to the user of the medicament dispenser.

2. The dose indicator assembly according to claim 1, wherein driving cam comprises driving studs configured to rotate the dummy wheel.

3. The dose indicator assembly according to claim 1, wherein the dose indicating means provides a count ranging from numbers‘O’ to‘200’ which are displayed synchronously and simultaneously.

4. The dose indicator assembly according to claim 1, wherein the dose indicating mean comprises a scroll having an ascending or descending read-outs, printed or etched or embossed or colored thereon.

5. The dose indicator assembly according to claim 4 wherein the dose indicator assembly further comprises a driving roller shaft, a driver roller shaft, a driving shaft guide, a driven roller shaft guide and a wheel lock to prevent reverse rotation of the scroll.

6. The dose indicator assembly according to claim 1, wherein the plunger is a spring loaded plunger which moves in the rectilinear motion during the actuation of the medicament dispenser.

7. The dose indicator assembly according to claim 6, wherein the plunger is driven either by the press and breathe operation by the user or by breath actuated mechanism of the medicament dispenser.

8. The dose indicator assembly according to claim 7, wherein a cam plunger link connects the plunger to the driving cam.

9. The dose indicator assembly according to claim 1 wherein the driving cam comprises a driving stud that rotates the dummy wheel via radial ratchets of the dummy wheel.

10. The dose indicator assembly according to claim 5, wherein the dummy wheel rotates the driving roller.

11. The dose indicator assembly according to claim 10, wherein rotation of the driving roller causes the scroll to advance over the driven roller from the driving roller providing a dose related visual feedback to the user of the medicament dispenser.

12. The dose indicator assembly according to claim 5, wherein radial ratchets of the dummy wheel together with the wheel lock prevent the reverse rotation of the driving roller.