GB2530980A - Simulated cigarette - Google Patents

Abstract

A simulated cigarette comprising a housing 1, containing a reservoir 2 configured to receive and contain a dose of inhalable formulation, a means for controlling flow from the reservoir, and outlet passage from said means to an outlet in the housing from which a user inhales, thus delivering the formulation by pulmonary administration, wherein a deliverable daily dose, using one or more simulated cigarettes, comprises less than 60mg of nicotine, preferably 40 to 18mg or less. Preferably the deliverable daily dose is a maximum daily dose and the dose is received from a refill pack containing preferably 2 to 20mg of nicotine. The daily dose of inhalable formulation can be provided by 2 or 5 refill packs, or the refill pack may contain 15 to 30 doses. A dose may comprise 0.1 to 1mg, or 0.2 to 0.7mg nicotine and subsequent doses may comprise 0.66 to 0.69mg, 0.21 to 0.23mg or 0.43 to 0.45mg nicotine. Each dose may be consumed at a rate of one inhalation every 15 seconds for up to 4 minutes. Preferably the simulated cigarette further comprises a breath actuated valve, heater 6 and power source 9, and the composition comprises ethanol, propylene glycol and a propellant such as HFA.

Description

Snn&ats Uu ette the invention relates to a simulated cigarette for effectively delivering a safe daily dose of an inhalahie formulation comprising nicotine.

the smoking of tobacco is an addictive activity associated with thc pieasurabe teeing caused by nicotine, and reinforced by the habits and rituals of the smoker. These attributes combine to make it very difficult to give up smoking, despite the numerous adverse health effects of the carbon monoxide. tar, and other combustion products of tobacco. it is not the nicotine itself that is harntful to health, rather the by-products of tobacco smoke.

There are a number of smoking cessation aids currently on the market for use in effctive nicotine replacement therapy (NR'[), such, as mcotme skin patches, nEcotme-containmg gums, nicotine cartridues. and nicotine simulated cigarettes. These aids attempt' to achieve the increase in blood nicotine content provided by tobacco smoke without the associated dangerous ny-products. Among the various modes of'NRT, nicotine inhale.rs most closely replicate thc rituals ofsmoking. A class of nicotine inhalers are tenned vaporizers' or electronic cigarettes'. In electronic "e"-cigareltes, as is the case in ot vents Ml ooaeco igaiet..e', n ene rust Ic heated ir order to he ora y to a user (to result iii combustion in the case of a conventional cigarette or to result in vnonsrion in the case of an c-cigarette) Such hcatng results in the gercration o harinlid by-products, such as aldehydes, ketones, nitrosamines and heavy metals, which are then also delivered to the user via inhalation, *Thus, there are otental health conse-queMes of using ecigarettes as NRT.

The present invention provides a simulated cigarette fbi use in NRT. Thus, the present invention provides a simulated cigarette comprising a housing having a generafly cigarette-like shape and size a reservoir within the housing configured to receive and contain a dose of inhalahie formulation; a moans for controlling the flow from the reservoir; an outlet passage from the means thy controlling the flow from the. reservoir to n outk in ti c housing troT htch cut eta usr inhak e hrm at on wherur a deliverable daily dose of inhalable fonnuiation is delivered by pulmonary administration usi g one or more of saul si ml ted cgaiUte wherein said de ivei able daily dose comprises ess than 60mg of nicotine or a pharmaceutically acceptable salt thereof Each aspect or embodiment as defined herein may be combined with any other aspect(s) or embothmentts) unless clearly indicated to the contrary. In particular any fealure indicated as being preferred or advantageous may be combined with any other feature or feaurres indicated as being preferred or advantageous.

It has been surprisinsly Found that the simulated cigarette according to the prese.n.t invention delivers a highly consistent do& of nicotine to the user, and when used in the manner of the present invention are capaWe of relieving or preventing nicotine craving associated with tobacco dependence using lower doses of nicotine than in known orally inhalable NRT modes, When used according to the dosing regimen described herein, the Mescntl aimed ornLlacd ga cUe is apah!e of rLplLeing nan' oldie itua s associated with smoking, which provides a psycholosical boost to the physiological eileeN." the dUr'lnisLic meotine I h s erh es e'tectn re id O niLonne cla%' ng ot flhdr IWY4 symptors asso iated wn toiaco dependenc.s ng o'er iant ties ot nicotine than are required to achieve the same kvel of relief in dosage regimens known for existing orally inhaiablc nicotine ftnTnuiat.ions, In another aspect of the present invention, the reservoir receives said dose of inhalahie fonnulation from a refill pack.

The term "diameter' as used herein encompasses the largest dimension of a droplet, DropLet oiaiiter rUerred to hereir may tie measurci usin a Mthe"n Spiaytie clevce the teim "D 10 as ec herein iefer 0 3 droplet d aneter that no more thcn C %ol ci the droplets in afbrmulation have a smaller diameter than. The term "Dv50" as used a herein reibrs to a droplet diameter that no more than 50 %voi of the droplets in a formulation have a smaller diameter than. The term "Dv90" as used herein refers to a droplet diameter that no more than 90 %voi of the droplets in a formulation have a smalk' diameter than Dv 10, Dv 50 and)v90 v'du may he dctc r ind usmt a \lalv tin Spraytec device, The term "nicotine free base" as used herein refers to the form of nicotine that predominates at high p1-i levels, he. at phi levels above 7.

The Lerm "C,,.a," as used herein refers to the maximum measured concentration of a compound, in this case nicotine, in the boodstream of a subject.

The term "t," as used herein refers to the time iaken to achieve C, fioni admrn straflon o' the comound The terms "patient", "subject" and "user" are used interchangeably herein, and refer to an animal, preferably a human, to whom NRT is applied 1' he term "deliverable daily dose" means the euniulati%e amount of nicotine that is pulminarily administered to the user over the course of a 24 hour period. According to aspects oi'the p-resent invention the inhalable fbrmulation is released from the refill pack into the reservoir of a simulated cigarette by action ala pressure gradient between the two devices. The deliverable daily dose of nicotine is the amount of nicotine that can be transferred tint the rePH pack to the user via iterative doses of an empty reservoir of a simulated cigarette, accounting for escape of formulation during refils.

When introducing elements of the present disclosure or the preferred embodiments(s) thereof the articles a", "an", the" and "said' are intended to mean that the-re are one or more of the elements. The terms "comprising", including" and "having' are intended to 4.

he inclusive, and mean that there may be additional elements other than tile listed elements.

The present invention pro4des a simulated cigarette, comprising: a housing having a generally cigarette-like shape and size; a reservoir within the housing configured to receive and contain a dose of irihaiahle tormulaton; a means for conrrollmg the flow from the reservoir; an outlet passage from the means for controlling the flow from the reservoir to an outlet in the housing from which outlet a user inhales the formulation, wherein a celwerable dai:y dose at mhaiahle rormnulation is denvered by pulmonary acmnustrauon using one or more of said simulated cigarettes, wherein said deliverable daily dose comprises!ess than 60mg of nicotine or a phannaceutically acceptable salt thcreof.

iii an embodiment of the invention, the reservoir receives said dose of inhalable formulation from one or more refill packs, such that the deliverable daily dose is contained in said one or more refill packs.

According to one embodiment of the uresent invention, the total content of nicotine or a pharmaceutically acceptable salt thereof of the daily close contained in the one or more refill packs is 0,2 mg or more and does not exceed 75mg, 70mg. 65mg, 60mg, 55mg.

50mg. 45mg, 40mg, 35mg, 3Oma, 25mg, 20mg, 19mg, 18mg, 17mg, 16mg, 15mg, 14mg, 3 ng 2mg, II na, lOng 9 Sn g 0mg h Sing, Snm, 2 g 7mg, 6 5mg, orh, 5mg, 4.5mg 4mg, 3.5mg. 3mg, 2.5mg, 2mg, 1.5mg, 1mg, 0.9mg, 0.b'rng, 0.7mg, 0.6mg, 0.5mg. 0.45mg, 0.4mg, 0.35mg, 0.3mg. or 0.25mg.

In an embodiment of the invention, the deliverable daily dose of nicotine or a phaimaect'ucally acecptcblc salt t it coin, a. least 60%, p eferab.y at lea\t 70%, more picferahly at least 75% of the total dose of nkotlre oi pharn a..eutiuall acceptable salt thertot cn arcc in th nkal thie forudahon previdd m the ore r m c icfL' PC cks a Iii an asnect of the present nvenuon the tu y dc's ot rha tHe tormulat'o" comr.tses a deliverable daily dose that is 0.2mg or more, and does not exceed 60mg 55mg,SOmg, 45mg, 40mg, 35mg, 30mg, 25mg, 20mg, 19mg, 18mg, 17mg, 16mg. 15mg, 14mg, 13mg, 12mg, 11mg, 10mg, 9.5mg, 9mg, 8.5mg, 8mg. 7.5mg. 1mg, 6.5mg, 6mg, 5.5mg, 5mg.

4.5mg. 4mg, 3.5mg, 3mg, 2.5mg, 2mg, .5mg. 1mg, 0.9mg, 0.8mg, 0.7mg, 0,6mg, 0.5mg, 0.45mg, 0.4mg, 0.35mg, 0.3mg, 0.25mg or 0.2mg. In a prctbrred embodiment, the deliverable daily dose is 40mg or less, preferably 20mg or less, more preferably I 8mg or less, in some embodiments when using the simulated cigarette of the present invention the subject is free to seIfadminister a dose that is lower than the daily dose provided herein, and the daily dose described herein is a maximum daily dose, In an. aspect of the present invention, the simulated cigarette delivers a deliverable dose of nicotine or pharmaceutically acceptable salt thereof which is substantially temperature independent. In an embodiment of the invention, the simulated cigarette delivers a deliverable dose wnieh is constant across a temperature range of from about 15°C to about 2.00°C, preferably about 1 5°C to about 180°C. more prelbrably from about 20°C to about 80°C. Accordingly, in an embodiment of the invcntion the methods and dosage regimens of the present invention are administered at a temperature of 50°C or less, preferaHy 37°c or less more prof eraHy 30°C r less Alter atn'J, the formulati i heated to a tempe auie of uncle 180°C us ig a eatn g leme"t comor sed v the hoisn-', such that some or all components of the fbrmulation arc volatilized. Preferably the formulation is heated to 80°c, In embodiments ofthe present invention, a refill pack may comprises from about 2mg to about 30mg, or about 2mg to about 25mg, or about 2mg to about 20mg. or about 3mg. to a do.. t ng abou.. 4ma t.. ahou' 18mg or about Sm: to about i ng 0' ant ut brig to about 16mg, or about 7mg to about 15mg or about 8mg to about 14mg, or abc/Lit 8mg to about 13mw., or about 8mg to about 12 mg, or about 8mg to about 11mg, or about 9mg to abo J 0'r' "cotm O a ph.'rmaut calls aeceptab e theieof preferred embodimems, the refill pack may comprise about 13mg to about 20mg, preferably about 16mg to ahcaa 18mg, more preferably about 17mg to about 1 8mg nicotine or a pharmaceutically acceptable salt thereof. In an alternative prcfbrred embodiment, the refill pack may comprise from about 7mg to about 14mg, preferably about 8mg to about 13mg, more preferably about 11mg to about 12mg nicotine or a pharmaceutically acceptable salt tIlere(f. ian alternative preterred embodiment, the refill pack may comprise from about 2mg to about 7mg, preferably about 3mg to about 6mg, more preftrahiy from about 4mg to about 5mg nicotine or a phannaceuticailv acceptable salt thereof According to the present invention, the deflverable dose of nicotine or a pharmaceutically acceptable salt thereof provided by the refill pack is at least 60%, preferably at least 70%, more preferably at Least 75%, more preferably at least 78% of the total amount of nicotine or pharmaccuicafly acceptable sait thereof contained in the refill packs.

In particularly preferred embodiments, the refill pack comprises from about 16mg to about 18mg nicotine or a pharmaceutically acceptable salt thereof and provides a deliverable dose of at least 75%. preferably at least 78% of the total amount of nicotine or pharmaceutically acceptable salt thereof contained in the refill pack. In alternative prerrt a tmoodlmaa tic rJill pack c mpnscs from about 1mg to ih u' 12 ng nicotine or a pharmaceutically acceptable salt thereof and provides a deliverable dose of at least 73%, preferably at least 78% of the total amount of nicotine or pharmaceutically acceptable salt thereof contained in the refill pack. in alternative preferred embodiments, the refill pack comprises from about 4mg to about 5mg nicotine or a pharmaceutically accentable aP hcrol and p ooa.' e nerahie dose mat ea 75%, nteteta5l\ at east 78% of the total amount of nicotine or pharmaceutically acceptable salt thereof contained in the reflhl pack.

The one or more refill packs may consist of the number of refill packs necessary for a dcli red eel y dose of nhalab,g fcrmua ion &ccrdtng o the piecent irvcntion me preferred embodiment of the invention, the total nicotine content is such that the delivered daily dose of the present invention is provided in two refill packs. in an alternative preferred embodiment, the refill packs comprise from about 2mg to about 7mg nicotine or a pharmaceutically aeccptaHc salt thereof, and the deLivered daily dose of inhalable formulation is provided in five refill packs, or alternatively in four refill packs.

In an embodiment of the present invention, the refill pack comprises from about 5 doses to about 40 doses, wherein a dose is an amount oflnhalahle formulation necessary to fill the reservoir ofa simulated cigarette, In a preferred embodiment the refill pack comprises from about 10 doses to about 35 doses, or about 15 doses to about 30 doses, or about 17 doses to about 25 doses ofinhalahie ibrmuiation, In a preferred embodiment the refill pack comprises aporoximately 20 doses of inhalable tbrmulation.

in one embodiment of tac present invention each dose comprises approximately 0.imgd mg nicotine or a phanriaceutically acceptable salt thereof; or approximately 02mg--0.9mg, or approximately 0.3mg-OSmg, or approximately ft3mg-0.7mg, or approximately 0.4mg- 0.6mg. or approximately 04mg-ft5mg, or approximately 0.4 -06mg nicotine or a phanna.ceutically acceptable salt thereof In a preferred embodiment each dose comprises approximately 066mgM.ô9rng nicotine or a pharmaceutically acceptable salt thereof, or approxmatek' 043rng-0.45 mg ntcottne or a pharmaceuttcally acceptable sa it thereof; or approximately 0.21 mg-*0.23 nicotine or a phrirmaceutically acceptable salt thereof 1n one e nhodaner i ot t"c pres.nt invnHo, ili fi4 do'<e admwntyed o a a ni kited cigarette acord If 0 thc n cnt rs& men s"niprlse ss nieot'ne than Crc secord ant subsequent doses. Thus, in an embodiment of the invention, the first dose comprises less Ilum approxtmately I mg nicottne or a pharmaceutically acceptable salt thereof, preferably less than approximately 0.43 tug, more preferably approximately 0M2-0.3 rng.

In thcsc cm xxi nent the -Lc nd and sukscqueni dost s tray ( mfnse appi 0' riately 0.1 mg I tug nicotine or a pharmaceutically acceptable salt thereof, or approximately ft2mg-09mg, or approximately 0,3mg-0.Bmg, or approximately 03mg-0Ymg, or approximately 0.4mg-0.bmg, or approximately ft4mg-0.Smg, or approximately 0.4-C ómp flt( tine r a pharmaecu icalT accitabk,alt te ot prodd tha the a uo Inc content of the first dose is less than the second and subsequent doses. In a preferred embodiment the first dose comprises less nicotine or a pharmaceutically acceptable salt thereof than the second and subsequent doses, wherein the second and subsequent doses comprise approximately 0.66mg*-0.69mg nicotine or a pharmaceutically acceptable salt thereof, or approximately 043mg.-045 tug nicotine or a pharmaceutically acceptable salt thereof or approximately 0.2lmg-0.23 nicotine or a pharmaceutically acceptable salt ttiereof, in a preferred embodiment of the invention, each dose contains approximate y 5-15 inhalations, preferably approximately 6-12 inhalations, more preferably approximately T 10 inhalations, more preferably about $ inhalations or about 9 inhalations, In a preferred embocument each dose is consumed at a rate of approximately one inhalation per 0.05 minutes to one inhaiation per 2 minutes, preferably approximately one inhaistion per 0,1 minutes to one inhalation per 1 minutes, preferably approximately one inhalation per 0.2 minutes lo one inhalation per 0.5 minutes, more preferably approximately one inhalation per 0,25 minutes. hi a prelbrred embodiment of the invention each dose is consumed over a period of up toiC minutes, or up to 6 minutes, or up to 5 minutes, and preferably up to 4 rntnutcs, more preterably up to 3 minutes and more preferably up to 2 minutes.

Typically at least sonic (such as, for example, at least 10 %vol) of the droplets have a size of Iron C i to pm Such atop Us rna be £pe ted in the det, lung, and art therefoic particularly able to enter the blood stream via the pulmonary route. Fypically at least onn tuch a', mi L\amp.1 leasr 10°'ni l; of the dropltt have a cii imea of 1pm 04 to 0.5 urn, Such droplets are particularly able to mimic the pnarmaeokmeuc profile of a conventional cigarette, since conventional cigarette smoke has a mean particle diameter in the range offrorn 0.4 to 0.5 tm.

Whci hv 4o nuLtia ict the p'eser nyc men is delitet:d to usu yia one of the simulated elgarenes described below, the droplets may exhibit the following droplet size profile: Dv 90 of less than 20 inn, typically less than 5 m, more typically less than 3, even more tynieally less than 29 pm, and/or Dv 50 of less than 6 rim, typically less than 0 pm, more typically less than 0.7 p-i, er nioi e tp'a'1y less t"ar 0 6 ri, and/o? Dv 10 of iess than 2 pm. typically less than 03 pm, more typically less tItan 0,25 pm, even more typically less than 0,2 pm.

This particular droplet size profile is similar to the particle size profile of tobacco smoke.

Accordingly. the pharmacokinetic profile of the delivered formulation closely mimics that of a conventional cigarette. In particular, delivery of the formulation to a user generates an extended. peak of' high nicotine concentration with a short i,e. the time from first inhalation to the maximum nicotneplasma level, As a result, the formulation is highlv effective for usc hi NRT and is capable of effectively relieving nicotine craving associated with tobacco dependence or wilhdrawai symptoms associated with tobacco dependence at lower deliverable doses of nicotine than other orally inhalable modes of NRT.

tn a further aspect. the refill pack may comprise a pressurised container containing the formulation to refill the reservoir of the simulated cigarette wit]i the inhalable form ulat ion.

The pressurised container oflhe present invention may take the form of a pressurised canister, for exampie, a pressuriscd aluminium canister, The canister may be fully recyclable and/or reusable. The canister may be refilled as required by a vending ifs machine or a larger container coiuainrng the desired {brrnulation under a high pressure eralic U J one rn'oe mnI the canister is ar AW501 lirirnurn canister The pressun'sed container may he capable ordispensing the fbrmulation as a mixture of ijerosolised droplets. Preferably, the mixture has a particle size distribution that s similar to tobacco smoke, The mixture may have the appearance of a vapour or smo&e.

The pressurised container may be pressuriserl to a pressure of from 3 x I 5 Pa to 1.5 x i(Y Pa, preferably from 5 x I o Pa to 2 x 1 0° Pa, more preferably from 5.5 x I C' Pa to i x I (l's ia Pa, even more preferably at about 6 x 100 Pa.

Pref ibly die s ulalsd ugarvk is onflgurcd to cje drlets offc' mulat'on aercrum n which at least 97 ?4vol of the droplets have a diameter of less than 10 urn, preferably at least 98 %vol, more preferably at least 98.5 %vol, even more preferably at least 99 %vol.

Droplets of diameter less than 10 pm are deposited in the lungs, meaning that a pharrnaeokinetic profile similar to that of a conventional cigarette is provided.

Preferably the simulated cigarette is configured to eject droplets of formulation therefrom having the following size profile: Dv 90 of less than 20 pm, preferably less than 5 am, more ureferably less than 3 pm, even more preferably less than 2.9 pin, and/or Dv 50 of less than 6 pm, preferably less than 0.& pm, more preferably less thai 0.7 pm. even more preferably less than 0.6 pm. arid/or Dv 10 of less than 2 pim preferably less than 0.3 pm, more preferably less than 0 S 11 ccr mole ptet abi) h.ss than 02 urn Accordingly, in one embodiment, the simulated cigarette is configured to eject droplets with the ibliowing size prcrflle: Dv 90 <20 pm, Dv 50 <6 pm and Dv 10<2 pm; preferably with the thllowing size profile: Dv 90 < 5 pin, Dv 50 c 0.8 pin and Dv 10 < 0.3 pm; more preibrably with the following size profile: Dv 90 <3 pm, Dv 50 <0.7 pm and Dv 10< 0.25 urn; even more preferably with the following size profile: Dv 90 <2.9 un, Dv 50 <0.6 urn and Dv 10< 0.2 urn, Such a size profile is similar to that of a conventional cigarette, meaning that the pharmacokinetie profile provided closely mimics that of a conventional cigarette.

The simulated cigarette may provide a user with a nicotine arterial c. of up to 1.5 ag/mi, typically from 2 to 10 ng/ml, or even from 4 to S ng/mi. values greater than about 2 ng/ml provide a user with a head rush" as experienced when smoking a conventional cigarette.

The simulated cigarette may provide these C,. values with a i,,,< of from 10 seconds to minutes. typically from 5 minutes to iS minutes, often about 12 minutes. Compared to simulated cigareffe devices of the prior art, such 4,, values are closer to those exhibited by conventional cigarettes, Accordingly, the present invention more closely mimics the pharmaeokinetie profile of a conventional cigarette, and is therefore particularly effective for use in NR'i' or as an alternative to recreational smoking of' eonvention& cip,arcttes.

Preferably the simulated cigarette is configured to eject formulation therefrom at a rate of from 0.5 to 3 litres per minute. This rate is similar to the rate smoke is ejected from a conventional cigarette, Preferably the simulated cigarette is con ligured to provide an inhalation resistance of from I to 7 icPa, preferably about 4 kFa, Ibis inhalation resistance s nmlar 0 that p ovidL 3 y a couw itional eig te Vt'a n ft sin uktted. gaettt. Is configured to have the above ejection rate and/c'.r inhalation resistance, preferably the simulated cigarette is configured to deliver nicotine to a user at a rate of from 0.01 to 0.06 mg/mI. This is less than a conventional cigarette, However, since the habitual aspects of stroking have been mimicked by the above cjection rate and inhalation resistance, a user will experience the same level of satistactton with a lower level of inhaled nicotine in comparison to conventional srnokina cessation aids, In an embodiment of the present invention, the simulated. cigarel.te is configured to prc'ide a.msc crcot v,tl a meoti e veiou C., o up to 15 ig'ml and/Dt w di a of from 10 seconds to 20 minutes.

In one embodiment, the inhaiahle composition comprises a propellant, In another embodiment, the inhalabie composition comprises a solvent. In a preferred embodiment the soh'ent comprises a a monohydric alcohol; and a glycol and/or glycol ether, eharaeterised in that the ratio of monohydrie alcohol glycol and/or glycol ether by weight is from 6;l to 1:1.

in a preferred embodiment, the inhalable composition comprises nicotine or a pharmaceutically acceptable derivative or salt thereoi a propel kmit; a monohvdne alcohol; and a glycol and/or glycol ether, characterised in that the ratio of monohydrie alcohol glycol and/or glycol ether by weight is horn 6:1 to 1:1 A particularly preferred formulation comprises, based on the total weight of the formuLation: from 0.03 to 0.05 %w/w menthol, preferably about 0.04 %w/w, from 025 to 0.4 %w/w propylene glycol. preferably about 0.34 %w/w.

from 0.9 to I %w/w ethanol, preferably about 0.95 %w/w, saccharin, and ci then ififrorn DM25 %w/w to 0.03 %w/w nicotine or a pharmaceutically acceptable derivative or salt thereoi preferably about 0.028 %w/w, or (ii) from 0.054 %w/w to 0.058 %1w nicotine or a pharmaceutically acceptable derivative or salt thereof; preferably about 0.056 %w/w, or --13 (lii) horn 0.08 Yow!w to 0,088 %w!w nicotine or a Pharmaceuticafly acceptable derivative or salt thereof, preferably about 0084 %w/w, the balance being I WA-I 34a. wherein the ratio of nicotine to saccharin by weight is from 95:1 to 8:1, preferably about 8.75:1.

in an embodiment of the invention, the outlet passage is preferably a breathactivated valve.

In some embodiments the simulated cigarette has a breath-acflvated valve and the housing has an outlet end and an opposite end and the simulated cigarette further comprises: a formulation flow path for the flow of the formulation from the reservoir along the flow path arid out of the outlet at the outlet end of the housins; a flexible diaphragm within the housing defining an air flow path from an air inlet to an air outlet at the outlet end of the housing; a valve element movable with the diaphragm and biased by -a biasing force into a position in which it closes the formulation how path; wherein sueflon on the outlet end causes a flow through the air flow path providing a pressure differential over the valve element thereby lifting the valve element against the biasing force to open the formulation flow path; and wherein the biasing force is arranged to close the fOrmulation flow path once the suction ceases.

ProfOrably the simulated cigarette has a hreathactivaied valve and the breath-activated valve is a non-metered valve between the outlet and the reservoir, the breath-activated valve coinprtstng a flow path extem in' from tie ese ow 07 the o tiet e'd, t leat portion of the flow path heirg a defonnabl.e tube, and a clamping member which pinches the deformable tube closed when no suction force is applied to the device and releases the lube to open the flow path when suction is applied at the outlet, to provide uninterrupted flow from the rescrvcir to the outlet. This simulated cigarette is referred to hereinafter as a pmch valve" -imula eL ciga cUe Preferably the simulated cigarette further comprises a re-till valve in communication with the reservo!r via which the reservoir may he refilled. The simulated cigarette may he re-filled from a refill pack according to a Further asuect of the present invention.

Preferably the size of the reservoir, the pressure within the reservoir and the size of the outlet at its narrowest point are arranged so that, when the outlet valve is fully opened, the reservoir will discharge in less than 30 seconds.

In an embodiment of the invention, the simulated cigarette comprises a heating element and/or vibrating transducer to selectively volatilize at least some components of the fbrmulation, and a power source arranged to supply electrical power to the heater and/or vibrating transdt.icer when the user inhales from the simulated cigarette. The heater is preferably configured to heat the fhrmuiation to a temperature that will volatilise some, but not all, of the components of the formulation. This means that the temperatures required are less than those of the prior art. This thither reduces the power requirement of the simulated cigarette and prevents the degradation of the inhaled formulation. Thus, preferably, the heater Is arranged to heat the formulation to between 40 and 180°C and preftrably 40°C to 100°C, The ability to dispense at these temperatures is based on a recognition by the inventors that it is not necessary to volatilise all components of the formulation, Instead, the temperature is set at a level at which only certain components of the fhrmulation will volatilise.

Additionally or alternatively, other mechanisms may be employed to effect a fine aerosolisation of the non-voiatjhsed fbrmulaton components, :or example, the formulation may incLude a propellant to increase the pressure in the reservoir resulting in improved aerosolisation.

kiditrualk or elterna9vc y thee may be at leact one aufiow path arranged o d a' an n through the side of the cigarette as a user inhales from an inhaling end, and

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impinge on the formulation leaving the heater at. the inhaling end. Such airflow will reduce the mean particle size of the plume. Preferahy there is more than one such path, and preibrably the paths are arranged to generate swirl around the main axIs of the sunulated cigarette thereby generating further turbulence and causing greater reduction in particle size.

The airflow paths are preferably arranged to pass through a constriction in the vicinity of the outlet end of the simulated cigarette thereby generating a Venturi effect and promoting suchon of the fbrmulation out of the simulated cigarette. The simulated cigarette may he configured to have a throughtiow of air from one end to the other when the user inhales from the outlet end. However. preferably, one or both of the effect of the propellant in the reservoir and the Venturi effect provided by the airflow paths provides the motive force to expel the tormulaton from the reservoir.

file present invention also extends to a combnation of a simulated cigarette and a refill pack, the simulated cigarette comprising a reservoir for an inhalable composition, a heating Je nenttc, select vely ohtihse at least so're ecmpt nents of toe eo'ipos ion and at least one simulated cigarette capacitor arranged to supply electrical power to the heater when a user inhales from the simulated cigarette; the refill pack comprising a refill reservoir of inhalahie eomposit!on and a battery coupled to a refill capacitor, and being arranged to engage with the simulated cigarette and to refill the reservoir and recharge the snul,ted ctgirete capacitor fiom the ref 11 caa&itor whc em he heer is cofgrcd to heat the composition to a temperature that tvul volatilise some, but not all of the components of the Composition, wherein a deliverable daily close of inhalable composition is contained in one or more refill pack and is delivered by pulmonary adni inistration using one or more of said simulated cigarette, wherein said deliverable daily dose comprises less than 60mg of nicotine or a pharmaceutically acceptable salt thereoC The simulated cigarette cf this combination may have any of the preferred ibatures referred to herein. Preferably the pack is arranged to fully recharge and refill the simulated cigarette from empty in less than 30 seconds and preferably less than 10 seconds.

The bat-tery may he reehargable, but is preferably rori-reehargahie. Preferably, the refill reservoir is pressurised with a propeliant or a compressed gas, the simulated cigarette reservoir having a closable refill valve and the refill pack having a complementary refill valve such that engagement of the simulated cigarette with the pack will cause the two refill valves 10 open thereby allowing the pressurised composition to flow into the simulated cigarette reservoir. The refill nack is preferably configured such that it will automatically terminate thc ref-ill and recharge operations.

Preferably, the refill reservoir is pressurised with a propellant or a compressed gas, the sirnultcd g. tetle escrv a hay -g a closable req \alvc an the refill pek ha'ng a complementary refill valve such that engagement of the simulated cigarette with the pack will cause the two refill valves to open thereby allowing the pressurised composition to flow into the simulated cigarette reservoir.

The refill pack is preferably configured such that it will automatically terminate the refill and recharge operations. An exarnpe ofa combination eta simulated cigarette and refill pack will now be described with reference to the accompanying drawings, in which: Fig. I is a schematic cross-section eta simulated cigarette; Fig. 2 is a schematic crossscction ofa simulated cigarette within a refill pack; and Fig 3 is a a. 1 diagram toi the reehargir g oberanor I he srmulate-d c]garette s ni the term or a simulated cigarette navmg a generany cylindrical configuration the approximate size ofa cigarette. The simulated cigarette has a cylindrical housing I which may be in one or more pans. The housing may he wrapped with a paper-like wrap to provide a more realistic cigarette--like appearance and thel> Within the housing I is a reservoir 2 of inhMable composition. The reservoir 2 has an outlet 3, flow from which is controlled by a ball valve 4 which is opened by an electromagnetic actuator against the action crfa spring 5 which biases the ball valve 4 onto the ciullet 3. As an aflernative, the outlet vaNce may he a breath operated valve as mt do>c ostu w \ 0 0I 1/01 58>' and \ 02014 0 138 Downstream of the ball vaive 4 is a heater 6. This is made of any highiy efficient conductive material, preferably tibreglass, and has an internal pathway 7 along its central axis for the passaae of composition. The heating element 6 is powered by a super capacitor S (also known as an ultra-cap'acdor). A suitable capacitor is sold by Maxwell lechnologies as part of the HC series. This preferably has a capacity of3-7 F and a ciane&r,iffnm to 10mm rd a lenih of 5 to 50mm k it nev be moit than ore capacitor provided. Fig. I also shows an optional battery 9 which will charge the capacitor S. However, the current preference is for no battery to be present. The capacitor S is connected to the heater 6 by a wire 10. Cireuliry ii is provided to control the operation of the simulated cigarette.

The simulated cigarette has an inhaling end 12 and a refill end-13> The inhaling end is provided with an outlet orifice 14 which is in communication with the internal pathway 7 fror the heater. Surrounding the heater 6 in the vicinity of the irihahng end 12 are a number of air paths 15 as shown in Fig. 1. in practice. there may he a number of air paths arranged -around tire axis, but there are preferably 2 to 4 such pass-ages. These are angled with mspect to the main axis of t*-e simulated cigarette as shown. They may also he offset with respect to the axis such they gencrate a swirl of the air about the main axis. In particular, the air paths are configured to generate a cnturi effect eausir-.g suction in the internal pathway 7 of the heater 6 when a user inhales ire-rn the inhaling end 12.

The refill end is provided with a refill valve 16 in the form ofa ball valve which opens against the action of a spring 17 which biases the valve closed onto a refill nozzle 18. The refill valve 16 is connected to the reservoir 2 by a refill conduit 19 which extends past the capacitor S to provide fluid communication between the refill nozzle 8 and the reservoir 2:..A pair of electrical contacts 20 with exposed ends 21 are arranged to provide an electrical conncction from the refill end 3 to the opposite termmals of the capacitorS. When a uscr inhales from the inhaling end 12, air flow is detected by a sensor switch (not shownl in the air flow path 15 triggering the current flow from the capacitor S to the heater 6 in order to heat the composition, The composition or pflsL s 3thanol botH g pc nit 78 4 C), iLc'tme (hoilir a point 24 7°C) piupyene glycol (boiling point 188°C) and HFA (boiling point -26°C). Thus, by heating the composition to a tcmpcraturc of under 180°C, all hut the nicotine and propylene glyo±enc are volalibsed Prckrah y r c iposnsm is hmitec to 80°C viich v comprise the ethanol but not the propylene glycoh The result of this heating is a mixture of nonvolathised liquid fbrmatiori and vapour.

At the same time, the ball valve 4 is opened by the electromagnetic actuator, Thus, the composition in the reservoir 2, which may be pressurised to fcn-example, 6 bar if a propellant is used, leaves the reservoir along the internal pathway 7 assisted by the suction Force generated by the airflow in the air paths 15. ibis airflow also serves to hreak up the composition ensuring that the plume emItted from the outlet orifice 4 has a aeroso isatton 1ra nio oLs ugl v t mo iary deno flon The refill pack will now he dcscrihed by reference to Fig, 2, This shows the siniulakd cigarette of Fig. I inserted into the rcfl1 pack with the refill end 13 lowennost, The refill pack ms af pr'xurately tee sic and shape ii a c{ indart ci retfr pee hut a'n ave any configuration.

The refill pack comprises a housing 30 and is broadly divided into three sections namely, from lefl to right (in Fig. 2), a storage port:31 to receive the simulated cigarette, a power supply i 4accpQ*n retTh3& j%o arc connected across: the base:ofthehousfiig :39 as tacribed below.

The ersupptr3tcadatr4ih s:cha * thebfr:fl as shqwn in Els C 4iSfly36 i:d resenqfr* ! pis'$$d by a plqg3 i:whlth:4bwnwardEy by:aspting:39 bet MccbyascrScap4& The bottom cniSfthe reservoir istconreaed byta refill duct4l j:gfift valn4 14 beneath th muEt c,çpp 31. tiictè4l valve 41s flvM whhis4iasi: ekised by aspringad which Wøpenedin use by f erefill nosle 1$ f$* siinàlated cijrette which presses dbnwardiy eu the refill vake 4.

A t1cssptIng 43 Is pitvkS in thflouIng 30 uitdenieath the siiütatS cigarette iS r 3tThpIp$wiiipuswslnwtateflinnway*onThnefithngpSdon to a stotage: tth wki St t tug: tpl* This:iy. be itt. thrcxan'uple byreleSrug the:sthmtatedcLgrette whenta:Sn pS is detS:whIckiadcates Stt tofu; tin i os$ot Whets hen ser ir2i: b clgatetteisinsertedlnw thc hoting: 34) ht ot&thtonsh6*ñ iii F;2a dt to ovcftOt: tltftlcase:sjng42. Th ifihlnOElc l8:Opth:t1te tflll: vaLve 42:sitthThauhe pteitirWiñThe I öir 33 iisuffleióttóflft St refill ElVo t6iiVthó:*ithUIá óia* 2 thereby allowing composition to flow alongThe refill conduit t áád lThkt&the :25 rescrvoirt ThefrefiWopcratibwWautomailc&lyterminatcdasdesclibed above and the sleasespthgisrges the simul*e4c1prewto the Storagc:pothtitht At the same tune as the simulated cigarette is being refilled, the ends 21 of the electr,cat c$iZQ cS 44 pJ outer 45 charging pl$e the houSing :3ft, OhictarSeetai euptedió t:apr4I. ThU caw hesinwtzd øtt, capacitor S to be recharged sirnuhaneously with the refill. The recharge Circuit is shown in Fig. 3.