Patent Publication Number: US-11654243-B2

Title: Inner housing for a drug delivery device

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application is a continuation of U.S. application Ser. No. 14/812,133, filed on Jul. 29, 2015, which is a continuation of U.S. application Ser. No. 13/375,186, filed on Mar. 9, 2012, which is a U.S. National Phase Application pursuant to 35 U.S.C. § 371 of International Application No. PCT/EP2010/057456, filed on May 28, 2010, which claims priority to U.S. Provisional Patent Application No. 61/182,818, filed on Jun. 1, 2009 and European patent Application No. 09009042.4, filed on Jul. 10, 2009. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
    
    
     FIELD OF INVENTION 
     The present application is generally directed to dose setting mechanisms for drug delivery devices. More particularly, the present application is generally directed to a dose setting mechanism comprising an inner housing and used for drug delivery devices. Aspects of the invention may be equally applicable in other scenarios as well. 
     BACKGROUND 
     Pen type drug delivery devices have application where regular injection by persons without formal medical training occurs. This may be increasingly common among patients having diabetes where self-treatment enables such patients to conduct effective management of their disease. 
     There are basically two types of pen type delivery devices: resettable devices (i.e., reusable) and non-resettable (i.e., disposable). These types of pen delivery devices (so named because they often resemble an enlarged fountain pen) are generally comprised of three primary elements: (i) a cartridge section that includes a cartridge often contained within a housing or holder; (ii) a needle assembly connected to one end of the cartridge section; and (iii) a dosing section connected to the other end of the cartridge section. A cartridge (often referred to as an ampoule) typically includes a reservoir that is filled with a medication (e.g., insulin), a movable rubber type bung or stopper located at one end of the cartridge reservoir, and a top having a pierceable rubber seal located at the other, often necked-down, end. A crimped annular metal band is typically used to hold the rubber seal in place. While the cartridge housing may be typically made of plastic, cartridge reservoirs have historically been made of glass. 
     The needle assembly is typically a replaceable double-ended needle assembly. Before an injection, a replaceable double-ended needle assembly is attached to one end of the cartridge assembly, a dose is set, and then a dose is administered. Such removable needle assemblies may be threaded onto, or pushed (i.e., snapped) onto the pierceable seal end of the cartridge assembly. 
     The dosing section or dose setting mechanism is typically the portion of the pen device that is used to set a dose. During an injection, a spindle contained within the dose setting mechanism presses against the bung or stopper of the cartridge. This force causes the medication contained within the cartridge to be injected through an attached needle assembly. After an injection, as generally recommended by most drug delivery device and/or needle assembly manufacturers and suppliers, the needle assembly is removed and discarded. 
     Different types of pen delivery devices, including disposable (i.e., non-resettable) and reusable (i.e., resettable) varieties, have evolved over the years. For example, disposable pen delivery devices are supplied as self-contained devices. Such self-contained devices do not have removable pre-filled cartridges. Rather, the pre-filled cartridges may not be removed and replaced from these devices without destroying the device itself. Consequently, such disposable devices need not have a resettable dose setting mechanism. 
     In contrast to typical disposable pen type devices, typical reusable pen delivery devices feature essentially two main reusable components: a cartridge holder and a dose setting mechanism. After a cartridge is inserted into the cartridge holder, this cartridge holder is attached to the dose setting mechanism. The user uses the dose setting mechanism to select a dose. Before the user injects the set dose, a replaceable double-ended needle assembly is attached to the cartridge housing. 
     This needle assembly may be threaded onto or pushed onto (i.e., snapped onto) a distal end of the cartridge housing. In this manner, a double ended needle mounted on the needle assembly penetrated through a pierceable seal at a distal end of the cartridge. After an injection, the needle assembly is removed and discarded. After the insulin in the cartridge has been exhausted, the user detaches the cartridge housing from the dose setting mechanism. The user can then remove the empty cartridge from the cartridge retainer and replace the empty cartridge with a new (filled) cartridge. 
     Aside from replacing the empty cartridge with a new cartridge, the user must somehow prepare the dose setting mechanism for a new cartridge: the dose setting mechanism must be reset to a starting or initial position. For example, in certain typical resettable devices, in order to reset the dose setting mechanism, the spindle that advances in a distal direction during dose injection must somehow be retracted back into the dose setting mechanism. Certain known methods of retracting this spindle back into the dose setting mechanism to a restart or an initial position are known in the art. As just one example, certain known reset mechanisms require a user to turn back or push back (retract) the spindle or some other portion of the dose setting mechanism. 
     Resetting of known dose setting mechanisms have certain perceived disadvantages. One perceived disadvantage is that the pen device user has to disassemble the device to either remove an empty cartridge or somehow reset the device. As such, another perceived disadvantage is that such devices have a high number of parts and therefore such devices are typically complicated from a manufacturing and from an assembly standpoint. For example, certain typical resettable pen type devices are not intuitive as to how a user must replace an empty cartridge or how a user is to reset the device. In addition, because such resettable devices use a large number of components parts, such resettable devices tend to be large and bulky, and therefore not easy to carry around or easy to conceal. 
     There is, therefore, a general need to take these disadvantages associated with resetting issues into consideration in the design and development of resettable drug delivery devices. Such desired drug delivery devices would tend to reduce the number of component parts and also tend to reduce manufacturing costs while also making the device less complex to assemble and manufacture. Such desired devices would also tend to simplify the steps required for a user to reset a dose setting mechanism while also making the device less complex and more compact in size. 
     SUMMARY 
     It is an object of the present invention to provide an improved dose setting mechanism for a drug delivery device. 
     This object is solved by a dose setting mechanism comprising an inner housing with means for guiding a dial sleeve and/or a driver of said mechanism. 
     According to an exemplary arrangement (first embodiment), a dose setting mechanism for a drug delivery device comprises an outer housing and an inner housing having an external groove. The inner housing guides the driver to dispense a dose set by the dose setting mechanism. A dial sleeve is disposed between the outer and inner housing and is rotatably engaged with the external groove of the inner housing. When a dose is set, the dial sleeve is rotated with respect to both the outer housing and the inner housing. The dial sleeve is translated away from both the outer housing and the inner housing. Preferably, said external groove of said inner housing comprises a helical groove having a constant pitch. 
     The inner housing may comprise an internal surface having a mechanical configuration that guides said driver to dispense said dose set by said dose setting mechanism. According to a first aspect of this embodiment, said mechanical configuration of said inner housing comprises a spline that guides said driver to dispense said dose set by said dose setting mechanism. Alternatively, said mechanical configuration of said inner housing may comprise a groove that guides said driver to dispense said dose set by said dose setting mechanism. 
     To improve the mechanical properties of the dose setting mechanism, said dial sleeve may have a generally smooth outer surface. Preferably, a scale arrangement is provided along a portion of said generally smooth outer surface. According to a further aspect of this embodiment, said scale arrangement provided along said portion of said generally smoother outer surface is viewable only through a window provided in an outer housing of said dose setting mechanism. 
     The dose setting mechanism may be coupled to a cartridge holder. For a disposable drug delivery device, said dose setting mechanism is permanently coupled to said cartridge holder. 
     In addition, the dose setting mechanism may further comprise a spindle which is operatively coupled to said driver, such that when said inner housing guides said driver to dispense said dose set by said dose setting mechanism, said driver pushes said spindle to act on a cartridge bung while said spindle translates in a distal direction to expel said dose from said cartridge. 
     Independent from the above mentioned features of the first exemplary arrangement (first embodiment), according to a second exemplary arrangement (second embodiment), a mechanism for setting a dose comprises a spindle for acting on a cartridge bung and a driver cooperating with the spindle. The arrangement also comprises an inner housing having an inner surface. The inner surface of the inner housing dictating movement of the driver during a dose dispensing step so that the spindle acts on the cartridge bung. 
     Preferably, said inner surface of said inner body comprises at least one longitudinal groove. As an alternative, said inner surface comprises at least a portion of a helical groove. As a further alternative, said inner surface may comprise a male groove guide. 
     Independent from the above mentioned features of the first and second exemplary arrangement, according to a third exemplary arrangement (third embodiment), a drug delivery device comprises an outer body and an inner body having an external helical groove. A dial sleeve is engaged with the external groove of the inner body and positioned between the outer body and the inner body. A driving member is positioned within the inner body. A clutch is operatively coupled to the dial sleeve and the driving member. The clutch allows the dial sleeve and the driving member to rotate together during a setting of a dose of the drug delivery device. 
     In addition, a spindle may be provided operatively coupled to said driving member, such during said injection of said dose, said inner body guides said driving member and said driving member driver pushes said spindle to dispel a dose of medication from a cartridge. Further, said spindle may comprise at least one groove, said at least one groove allowing said spindle to translate in a distal direction to expel said dose from said cartridge. 
     Independent from the above mentioned features of the first, second and third exemplary arrangement, according to a fourth exemplary arrangement (fourth embodiment), a dose setting mechanism for a drug delivery device is provided comprising an outer housing, an inner housing, a driver and a dial sleeve. The inner housing has an external groove, with said inner housing being operatively coupled to the driver and guiding said driver to dispense a dose set by said dose setting mechanism. The dial sleeve is disposed between said outer housing and said inner housing, with the dial sleeve being rotatably engaged with said external groove of said inner housing, such that when a dose is set by said dose setting mechanism, said dial sleeve and driver are both rotated with respect to both said outer housing and said inner housing and are translated away from both said outer housing and said inner housing. Preferably, the external groove of said inner housing comprises a helical groove having a constant pitch. 
     According to a further development of this fourth embodiment, the inner housing comprises an internal surface, which comprises a mechanical configuration that guides said driver to dispense said dose set by said dose setting mechanism. The mechanical configuration of said inner housing may comprise a spline that guides said driver to dispense said dose set by said dose setting mechanism. As an alternative, the mechanical configuration of said inner housing may comprise a groove that guides said driver to dispense said dose set by said dose setting mechanism. 
     To improve the mechanical properties of the dose setting mechanism, said dial sleeve may have a generally smooth outer surface. Preferably, a scale arrangement is provided along a portion of said generally smooth outer surface. According to a further aspect of this embodiment, said scale arrangement provided along said portion of said generally smoother outer surface is viewable only through a window provided in an outer housing of said dose setting mechanism. 
     The dose setting mechanism may be coupled to a cartridge holder. For a disposable drug delivery device, said dose setting mechanism is permanently coupled to said cartridge holder. 
     According to a further aspect of this fourth embodiment a spindle is provided, which is operatively coupled to said driver, such that when said inner housing guides said driver to dispense said dose set by said dose setting mechanism, said driver pushes said spindle to act on a cartridge bung while said spindle translates in a distal direction to expel said dose from said cartridge. 
     A further aspect of the present invention is directed to the ratio of the length of the inner housing or body to the length of further components of the dose setting mechanism of a drug delivery device. Preferably, the inner housing has a length L in its axial direction which is essentially the same as the length of the dose setting mechanism, or the outer housing or the dose dial sleeve. Although it is preferred to choose the length L of the inner housing being nearly exactly the same as the length of the outer housing, preferred embodiments include a length L of the inner housing being between about 75% to about 125%, preferably between 90% and 110%, of the length of the dose setting mechanism, or the outer housing or the dose dial sleeve. 
     These as well as other advantages of various aspects of the present invention will become apparent to those of ordinary skill in the art by reading the following detailed description, with appropriate reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Exemplary embodiments are described herein with reference to the drawings, in which: 
         FIG.  1    illustrates a first embodiment of a resettable drug delivery device; 
         FIG.  2    illustrates the drug delivery device illustrated in  FIG.  1    with the cap removed; 
         FIG.  3    illustrates a sectional view of the first embodiment of the drug delivery device of  FIG.  2    in a first position; 
         FIG.  4    illustrates a sectional view of the first embodiment of the drug delivery device of  FIG.  2    in a second position; 
         FIG.  5    illustrates a sectional view of the first embodiment of the drug delivery device of  FIG.  2    in a third position; 
         FIG.  6    illustrates a first arrangement of the driver illustrated in  FIGS.  2 - 5    comprising a first driver portion and a second driver portion; 
         FIG.  7    illustrates a distal end of the spindle of the dose setting mechanism illustrated in  FIGS.  2 - 5   ; 
         FIG.  8    illustrates a sectional view of a second embodiment of a dose setting mechanism of the drug delivery device illustrated in  FIG.  1   ; 
         FIG.  9    illustrates a partial sectional view of the second embodiment of the dose setting mechanism illustrated in  FIG.  8   ; 
         FIG.  10    illustrates a close up view of Gap a illustrated in  FIG.  8   ; 
         FIG.  11    illustrates a second arrangement of the driver illustrated in  FIGS.  6 - 8    comprising a first driver portion and a second driver portion; 
         FIG.  12    illustrates the dose setting mechanism illustrated in either  FIGS.  2 - 5    or  FIGS.  6 - 8   , and 
         FIG.  13    illustrates the dose setting mechanism illustrated in  FIG.  12    in which a user has set a dose. 
     
    
    
     DETAILED DESCRIPTION 
     Referring to  FIG.  1   , there is shown a drug delivery device  1  in accordance with a first arrangement of the present invention. The drug delivery device  1  comprises a housing having a first cartridge retaining part  2 , and dose setting mechanism  4 . A first end of the cartridge retaining part  2  and a second end of the dose setting mechanism  4  are secured together by retaining features. In this illustrated arrangement, the cartridge retaining part  2  is secured within the second end of the dose setting mechanism  4 . A removable cap  3  is releasably retained over a second end or distal end of a cartridge retaining part. As will be described in greater detail, the dose setting mechanism  4  comprises a dose dial grip  12  and a window or lens  14 . To set a dose of medication contained within the drug delivery device  1 , a user rotates the dose dial grip  12  and the window allows a user to view the dialed dose by way of a dose scale arrangement  16 . 
       FIG.  2    illustrates the medical delivery device  1  of  FIG.  1    with the cover  3  removed from the distal end of the medical delivery device. As illustrated, a cartridge  20  from which a number of doses of a medicinal product may be dispensed is provided in the cartridge housing  6 . Preferably, the cartridge  20  contains a type of medicament that is administered often, such as once or more times a day. 
     The term “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, 
     wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a proteine, a polysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, an antibody, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound, 
     wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis, 
     wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, 
     wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exedin-3 or exedin-4 or an analogue or derivative of exedin-3 or exedin-4. 
     Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin. 
     Insulin derivates are for example B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. 
     Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Arg-Leu-Phe-Ile -Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2. 
     Exendin-4 derivatives are for example selected from the following list of compounds: 
     H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
     H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
     des Pro36 [Asp28] Exendin-4(1-39), 
     des Pro36 [IsoAsp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), 
     des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), 
     des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or 
     des Pro36 [Asp28] Exendin-4(1-39), 
     des Pro36 [IsoAsp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), 
     des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), 
     des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), 
     des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
     wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative; 
     or an Exendin-4 derivative of the sequence 
     H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2, 
     des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2, 
     H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
     H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
     des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
     H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2, 
     H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
     H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
     des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, 
     des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2, 
     H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
     H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
     des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
     H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2, 
     H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
     H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
     des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
     H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2, 
     H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2; 
     or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exedin-4 derivative. 
     Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin. 
     A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra low molecular weight heparin or a derivative thereof, or a sulphated, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. 
     Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g. salts having a cation selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are described in “Remington&#39;s Pharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology. 
     Pharmaceutically acceptable solvates are for example hydrates. 
     A bung or stopper (not illustrated in  FIG.  2   ) is retained in a first end or a proximal end of the cartridge  20 . 
     The dose setting mechanism  4  of the drug delivery device illustrated in  FIG.  2    may be utilized as a reusable (and hence resettable) or a non-reusable (and hence non-resettable) drug delivery device. Where the drug delivery device  1  comprises a reusable drug delivery device, the cartridge is removable from the cartridge housing  6 . The cartridge  20  may be removed from the device without destroying the device by merely the user disconnecting the dose setting mechanism  4  from the cartridge holder  6 . 
     In use, once the removable cap  3  is removed, a user can attach a suitable needle assembly to the distal end of the cartridge holder. Such needle unit may be screwed onto a distal end of the housing or alternatively may be snapped onto this distal end. A replaceable cap  3  is used to cover the cartridge holder  6  extending from the dose setting mechanism  4 . Preferably, the outer dimensions of the replaceable cap  3  are similar or identical to the outer dimensions of the dose setting mechanism  4  so as to provide an impression of a unitary whole when the replaceable cap  3  is in position covering the cartridge holder  2 . 
       FIG.  3    illustrates a sectional view of the dose setting mechanism  4  removably connected to the cartridge holder  6 . The dose setting mechanism  4  comprises an outer housing  40  containing a spindle  42 , a number sleeve  10 , a clicker  75 , a clutch  26 , and a driver  30 . A first helical groove  19  extends from a first end of a spindle  42 . In one arrangement, the spindle  42  is generally circular in cross section however other arrangements may also be used. The first end of the spindle  42  (a distal end  43  of the spindle  42 ) extends through a pressure plate  64 . A spindle bearing  50  is located at the distal end  43  of the spindle  42 . The spindle bearing  50  is disposed to abut a second end of the cartridge piston  18 . The driver  30  extends about the spindle  42 . 
     The clutch  26  is disposed about the driver  30 , between the driver  30  and a number sleeve  10 . The clutch  26  is located adjacent the second end of the driver  30 . A number sleeve  10  is provided outside of the clutch  26  and radially inward of the housing  40 . The main housing  40  is provided with a window  14  through which a part of an outer surface  11  of the number sleeve  10  may be viewed. 
     Returning to  FIGS.  1 - 2   , a dose dial grip  12  is disposed about an outer surface of the second end of the number sleeve  10 . An outer diameter of the dose dial grip  12  preferably corresponds to the outer diameter of the housing  40 . The dose dial grip  12  is secured to the number sleeve  10  so as to prevent relative movement between these two components. In one preferred arrangement, the dose dial grip  12  and number sleeve  10  comprise a one piece component that is rotationally coupled to a clutch and drive sleeve and axially coupled to the number sleeve  10 . However, alternative coupling arrangements may also be used. 
     Returning to  FIGS.  3 - 5   , in this arrangement, driver  30  comprises a first driver portion  44  and a second driver portion  46  and these portions extend about the spindle  42 . Both the first and the second driver portions  44 ,  46  are generally cylindrical. As can be seen from  FIG.  6   , the first drive portion  44  is provided at a first end with a first radially extending flange  56 . A second radially extending flange  58  is provided spaced a distance along the first driver portion  44  from the first flange  56 . An intermediate helical groove  62  is provided on an outer part of the first driver portion  44  extending between the first flange  56  and the second flange  58 . A portion or a part helical groove  68  extends along an internal surface of the first driver portion  44 . The spindle  42  is adapted to work within this part helical groove  68 . 
     A dose limiter  38  (illustrated in  FIG.  3   ) is located between the driver  30  and the housing  4 , disposed between the first flange  56  and the second flange  58 . In the illustrated arrangement, the dose limiter  38  comprises a nut. The dose limiter  38  has an internal helical groove matching the helical groove  62  of the driver  30 . In one preferred arrangement, the outer surface of the dose limiter  38  and an internal surface of the housing  40  are keyed together by way of splines. This prevents relative rotation between the dose limiter  38  and the housing  40  while allowing relative longitudinal movement between these two components. 
     Referring back to  FIGS.  2 - 5   , essentially, in normal use, the operation of the dose setting mechanism  4  occurs as follows. To dial a dose in the arrangement illustrated in  FIGS.  1 - 5   , a user rotates the dose dial grip  12 . The driver  30 , the clutch  26  and the number sleeve  10  rotate along with the dose dial grip  12 . In this preferred arrangement, the clicker  75  is disposed between a distal end  23  of the clutch  26  and a flange  80  of the drive sleeve  46 . The clicker  75  and the internal surface of the housing  40  are keyed together by way of splines  65   a,    65   b.  This prevents rotation of the clicker  75  with respect to the housing  40  either during dose selection or during dose administration. 
     The number sleeve  10  extends in a proximal direction away from the housing  40 . In this manner, the driver  30  climbs the spindle  42 . As the driver  30  and the clutch rotates, a distal portion  23  of the clutch drags over the clicker  75  to produce a click. Preferably, the distal portion includes a plurality of splines that are disposed such that each click corresponds to a conventional unit dose, or the like. 
     At the limit of travel, a radial stop on the number sleeve  10  engages either a first stop or a second stop provided on the housing  40  to prevent further movement. Rotation of the spindle  42  is prevented due to the opposing directions of the overhauled and driven threads on the spindle  42 . The dose limiter  38 , keyed to the housing  40 , is advanced along the thread  62  by the rotation of the driver  30 . 
       FIG.  2    illustrates the medical delivery device after a desired dose of 79 International Units (IU) has been dialed. When this desired dose has been dialed, the user may then dispense the desired dose of 79 IU by depressing the dial grip. As the user depresses the dial grip  12 , this displaces the clutch  26  axially with respect to the number sleeve  10 , causing the clutch  26  to disengage. However the clutch  26  remains keyed in rotation to the driver  30 . 
     The driver  30  is prevented from rotating with respect to the main housing  40  but it is free to move axially with respect thereto. The longitudinal axial movement of the driver  30  causes the spindle  42  to rotate and thereby to advance the piston  18  in the cartridge  20 . 
     In normal use, the first and second portions  44 ,  46  of the driver  30  are coupled together when the dose dial sleeve  10  is rotated. That is, in normal use, the first and second portions  44 ,  46  of the driver  30  are coupled together with the dose dial sleeve  10  when a user sets a dose by turning the dose dial grip  12 . After each dispensed dose, the spindle  42  is pushed in a distal direction, acting on the bung  18  of the cartridge  20  to continue to expel a dialed dose of medication out of an attached needle assembly releasably connected to the distal end  8  of the cartridge holder  6 . 
     After a user uses the drug delivery device  1  to dispense all of the medication contained in the cartridge  20 , the user may wish to replace the empty cartridge in the cartridge holder  6  with a new cartridge. The user must then also reset the dose setting mechanism  4 : for example, the user must then retract or push the spindle  42  back into the dose setting mechanism  4 . 
     If the user decides to replace an empty cartridge and reset the device  1 , the first and second driver portions  44 ,  46  must be de-coupled from one another. After decoupling the first driver portion  44  from the second driver portion  46 , the first driver portion  44  will be free to rotate while the second driver portion  46  will not be free to rotate. 
     During a device resetting step, rotating the first driver portion  44  achieves at least two results. First, rotation of the first driver portion  44  will reset the axial position of the spindle  42  with respect to the dose setting mechanism  4  since rotation of the first driver portion  44  causes the spindle  42  to rotate. Rotation of the spindle  42  (because the spindle is splined with the spindle guide  48 ) moves the spindle in a proximal direction back into the dose setting mechanism. For example,  FIG.  7    illustrates one arrangement for connecting the spindle  42  to the spindle guide  48 . In  FIG.  7   , the spindle  42  comprises a first spline  51  and a second spline  52 . The spindle guide  48  comprises an essentially circular member having an aperture. The aperture includes two inner protruding members  55 ,  57  that engage the first and second splines  51 ,  52  respectively, so that the spindle guide  48  locks onto the spindle and rotates along with the spindle during spindle rotation. 
     Second, rotation of the first driver portion  44  will also axial move or reset a dose limiter  38  to an initial or start position. That is, as the first driver portion  44  is rotated back to an initial start position, because the dose limiter  38  is threadedly engaged to the outer groove and splined to an inner surface of a housing portion, such as the outer housing  40 . In this configuration, the dose limiter  38  is prevented from rotating but will move along the outer groove  62  of the first driver portion  44  as this portion is rotated during a resetting step. In addition, because it is splined to longitudinal splines  65   a,    65   b  of the outer housing  4 , the clicker  75  is also prevented from rotating during this resetting step. 
     Referring to a first driver arrangement illustrated in  FIG.  3   , the two portions of the driver  30  are decoupled when the first driver portion  44  is pulled axially away from the second driver portion  46 . This may be achieved by the use of a biasing means (such as at least one spring) that interacts together when the cartridge holder  6  is removed from the front or distal end of the device to first lock the relative rotation between the spindle  42  and a spindle guide  48  through which the spindle passes, and then to push this spindle guide  48  and also nut  66  axially a fixed distance. Because the spindle  42  is rotationally locked to this spindle guide  48  and is threadedly engaged with the spindle nut  66 , the spindle  42  will move axially. 
     The spindle  42  is coupled via a groove engaged to the first driver portion  44 . The first driver portion  44  is prevented from rotation by a clutched connection to the second driver portion  46 . In one preferred arrangement, the second driver portion  46  is prevented from rotation by the clicker detent  75  which resides between the clutch and the flange  80  of the drive sleeve  46 . Therefore, axial movement of the spindle  42  decouples the two driver portions  44 ,  46  so that the clutched connection becomes de-coupled. 
     This sequence of operation as the cartridge holder  6  is removed or disconnected from the dose setting mechanism  4  is illustrated in  FIGS.  3 - 5   . In  FIG.  3   , the various component parts of the drug delivery device include: a dose setting housing  40 , a cartridge  20 , a spindle  42 , first driver portion  44 ; second driver portion  46 , spindle bearing  50 , spindle guide  48  a spring plate  54 ; a main spring  60 , a pressure plate  64 , a cartridge holder  20 ; a spindle nut  66 ; and a second spring  70 . In this preferred arrangement, the spindle guide  48  is rotationally fixed relative to the spindle  20 . In addition, the spring plate  54  pressure plate  64  and spindle nut  66  are all rotationally fixed relative to the outer housing. 
     In  FIG.  3   , the cartridge holder  6  is fitted via apertures in the pressure plate  64  and applies a load to the spring plate  54 . This compresses the first biasing means or main spring  60 . These apertures in the pressure plate  64  (not shown) allow the pressure plate  64  to move away from the spring plate  54  (in a distal direction towards the cartridge holder  6 ) under the action of the second biasing means or second spring  70 . This will open up a Gap “a” as shown in  FIG.  3   . Gap “a” is a gap created between the pressure plate  64  and the spring plate  54 . This will also open Gap “b”, a gap between the spindle nut  66  and the spring plate  54 . This Gap b is illustrated in  FIG.  3   . The Gap b in conjunction with the light force from the second spring or biasing means  70  moves the spindle nut  66  towards the distal end of the drug delivery device  1 . This applies light pressure to the spindle guide  48 . 
     The spindle guide  48  is compressed under the action of the second spring  70  between the spindle nut  66  and pressure plate  64 . This light force coupled with the friction coefficient on either side of a flange of the spindle guide  48  through which this force acts, provides a resistance to rotation of the spindle guide  48  and therefore a resistance to rotation of spindle  42  as well. One advantage of this configuration is that at the end of a dose, it is advantageous to prevent the spindle  42  from back-winding into the dose setting mechanism  4  under light residual loads that may remain from the cartridge bung  18 . By preventing the spindle  42  from back-winding in a proximal direction, a distal end  43  of the spindle  42  (and hence the spindle bearing  50 ) remains on the bung  18 . Maintaining the distal end  43  of the spindle  42  on the bung  18  helps to prevent a user from administrating a potential under-dose. 
     When the user delivers a dose, as the dispense force increases, the rearward load on the spindle nut  66  increases to a point at which the spindle nut  66  travels back in a proximal direction and compresses the second spring  70 . This releases the axial force acting on the spindle guide  48 . This removes the resistance to rotation of the spindle guide  48  and hence spindle  42 . This configuration therefore prevents back-winding of the spindle  42  under low loads caused by the cartridge bung  18  but does not add to the dispense force once this dispense force has increased above a certain threshold level. 
       FIG.  4    illustrates the dose setting mechanism  4  of  FIG.  3    with the cartridge holder  6  rotated to release a connection type between the housing  40  of dose setting mechanism  4  and the cartridge holder  6 . In one arrangement, this connection type  22  is a bayonet connection. However, those of ordinary skill in the art will recognize that other connection types  22  may be used as well such as threads, snap locks, snap fits, luer locks and other similar connection types. In the arrangement illustrated in  FIGS.  3 - 5   , by rotating the cartridge holder  6  with respect to housing  40 , features that were initially acting on the spring plate  54  to compress the main biasing means  60  through apertures in the pressure plate  64 , rotate so that they now release this force created by the main biasing means  60 . This allows the spring plate  54  to move in a distal direction until the spring plate  54  contacts the spindle nut  66  on an inside face of the spindle nut  66 . 
     In this second condition, the previous discussed Gap “a” (from  FIG.  3   ) has now been reduced to a Gap “c” (as seen in  FIG.  4   ). In this manner, the relative high axial force from the main biasing means  60  acts through the spring plate  54  to the spindle nut  66  and from the spindle nut  66  through the spindle guide  48  to the pressure plate  64 . This relative high axial force from the main biasing means  60  is sufficient to prevent the spindle guide  48 , and hence spindle  42 , from rotating. 
     After sufficient rotation of the cartridge holder  6 , the cartridge holder  6  disengages from the connection type  22  with the housing  40 . The cartridge holder  6  is then driven in an axial direction away from the housing  40  by the main biasing means  60  (i.e., in a distal direction). However, during this movement, the main spring  60  continues to load the cartridge holder  6  through the spindle guide  48  and therefore the spindle  42  is prevented from rotation. As the spindle  42  is also threaded to the first driver portion  44 , the first driver portion  44  is also pulled axially in a distal direction and in this manner becomes disengaged from the second driver portion  46 . The second driver portion  46  is axially fixed and is prevented from rotation. In one arrangement, the second driver portion  46  is prevented from rotation by clicker elements and prevented from axial movement by its axial coupling to the number sleeve. 
       FIG.  5    illustrates the dose setting mechanism illustrated in  FIG.  3    in a third position, that is, with the cartridge holder  6  removed. As the cartridge holder  6  is removed from the housing  40 , the bayonet features shown in  FIG.  5    (illustrated as round pegs extending radially inwards on inside of inner housing), limit travel of the pressure plate  64  but allows Gap “c” (as shown in  FIG.  4   ) to increase to a wider Gap “d” (as shown in  FIG.  5   ). As a result, Gap “e” develops. Gap “e” removes the high spring force created by the main biasing means  60  from the spindle guide  48 . The dose setting mechanism  4  in  FIG.  4    is now ready to be reset. 
     To reset this dose setting mechanism  4 , a user retracts the spindle  42  in a proximal direction back into the housing  40  by pushing on the distal end  43  of the spindle  42 . Therefore, during this re-setting step of the dose setting mechanism  4 , as the spindle  42  is pushed back into the dose setting mechanism  4 , the movement of the spindle  42  causes the spindle nut  66  to move back against a light spring force created by the second biasing means  70 . This movement releases the axial load and hence resistance to rotation from the spindle guide  48 . Therefore, as the dose setting mechanism  4  is reset by the spindle  42  rotating back into the dose setting mechanism  4 , the spindle guide  48  also rotates. 
     As the spindle  42  is pushed back further into the dose setting mechanism  4 , the spindle  42  rotates through the spindle nut  66 . As the first driver portion  44  is de-coupled from the second driver portion  46 , the first driver portion  44  rotates (with the flexible elements  102 ,  103  running on a conical surface groove  90  formed by the first annular ring  91  on the second half of the drive sleeve  46 ,  FIGS.  5  and  6   ). This accommodates the axial and rotational movement of the spindle  42 . 
     As the first driver portion  44  rotates during reset, first driver portion  44  also re-sets the dose nut. More specifically, as the first driver portion  44  rotates, the dose nut which is not rotatable since it is splined to an inner surface of the housing  40 , traverses along the helical groove  62  provided along an outer surface of the first driver portion  44  and traverses back to an initial or starting position. In one preferred arrangement, this starting position of the dose nut resides along the first radial  56  flange of the first driver portion  44 . 
     After the dose setting mechanism  4  has been reset, the dose setting mechanism  4  must be re-connected to the cartridge holder  6 . When re-connecting these two components, the process generally works in reverse. However, this time the axial compression of the main spring  60  causes the first driver portion  44  to re-engage with the second driver portion  46 . In this manner, the flexible elements re-engage with the second annular ring  94  on the second driver portion  46 . 
       FIG.  6    illustrates a first arrangement of the second driver portion  46  and the first driver portion  44  illustrated in  FIGS.  3   . As shown in  FIG.  6   , second driver portion  46  is generally tubular in shape and comprises a first annular groove  90  at a distal end of the second driver portion  46 . The first annular groove  90  comprises a conical face  91 . The second driver portion further comprises a second annular groove  94  and at least one spline  96  positioned along a surface of the second driver portion. 
     The first driver portion  44  is also generally tubular in shape and comprises a first and a second flexible element  102 ,  103  and a plurality of spline recesses  100 . These plurality of recesses  100  releasably connect the longitudinal spline  96  of the first driver portion  44  to second driver portion  46  when both first and second driver portions  44 ,  46  are pushed axially together so that they releasably engage one another. When pushed together, the flexible elements  102 ,  103  of the first driver portion  44  are pushed over the first annular groove  90  of the second driver portion  46  and then stop when the flange  80  of the second driver portion abuts the first axial flange  56  of the first driver portion  44 . 
     The first driver portion  44  also includes a plurality of ratchet features  104 . These ratchet features  104  are provided at a distal end  106  of the first driver portion  44 . These ratchet features  104  engage similar ratchet features on the spring plate  25  which are splined to the housing  2 . (See e.g.,  FIGS.  3 - 5   ) At the end of the re-setting step, these ratchet features engage one another so as to prevent the first driver portion  44  from rotating. This ensures that as the spindle  42  is reset further, the first driver portion moves axially to re-engage the second driver portion  46  rather than rotate on the conical face  90 . These features also orientate the spring plate  25  relative to the second driver portion  44  so that the two driver portions  44 ,  46  engage easily during assembly or after reset. Therefore, these ratchet features also prevent the coupling features  100 ,  96  from clashing with one another. 
     A second arrangement of resettable dose setting mechanism is illustrated in  FIGS.  8 - 10   .  FIG.  8    illustrates a section view of a second arrangement of a dose setting mechanism  200 . Those of skill in the art will recognize that dose setting mechanism  200  may include a connection mechanism for releasably connecting to a cartridge holder, like the cartridge holder  6  illustrated in  FIG.  2   . However, as those of ordinary skill in the art will recognize, the dose setting mechanism may also include a permanent connection mechanism for permanently connecting to a cartridge holder. 
       FIG.  9    illustrates a portion of the dose setting mechanism illustrating the driver operation.  FIG.  10    illustrates a close up view of the coupling between the first driver portion and the second driver portion illustrated in  FIG.  9   . The second arrangement of the dose setting mechanism  200  operates in generally a similar fashion to the first arrangement of the dose setting mechanism  4  illustrated in  FIGS.  1 - 5   . 
     With reference to  FIGS.  8 - 10   , the dose setting mechanism  200  comprises a dose dial grip  202 , a spring  201 , an outer housing  204 , a clutch  205 , a driver  209 , a number sleeve  206 , a clicker  220  and an inner housing  208 . Similar to the driver  30  illustrated in  FIGS.  2 - 5   , driver  209  of dose setting mechanism comprises a first driver portion  207  and a second driver portion  212 . In one arrangement, the first driver portion  207  comprises a first component part  210  and a second component part  211 . Alternatively, the first driver portion  207  is an integral component part. 
     Where the dose setting mechanism  200  illustrated in  FIGS.  8  and  9    comprises a resettable dose setting mechanism, the driver  209  is de-coupled from the dose setting mechanism  200  when the first driver portion  207  is pushed axially towards the second driver portion  212  (i.e., pushed in a proximal direction). In one arrangement, this may be achieved by pushing axially on a distal end of the spindle  214 . This does not require any mechanism associated with removal of a cartridge holder. The mechanism is also designed such that the first and second driver portions  207 ,  212  and the spindle  214  remain locked together rotationally during dose setting as well as during dose administration. 
     An axial force on the spindle  214  causes the spindle  214  to rotate due to its threaded connection to the inner housing  208 . This rotation and axial movement of the spindle  214  in turn causes the first driver portion  207  to move axially towards the second driver portion  212 . This will eventually de-couple the coupling elements  250  between the first driver portion  207  and second driver portion  212 . This can be seen from  FIG.  11   . 
     This axial movement of the first driver portion  207  towards the second driver portion  212  results in certain advantages. For example, one advantage is that the metal spring  201  will compress and will therefore close the Gap a illustrated in  FIGS.  8 - 10   . This in turn prevents the clutch  205  from disengaging from the clicker  220  or from the number sleeve  206 . As illustrated in  FIG.  9   , a distal end of the clutch  205  comprise a plurality of clutch teeth  203 . These clutch teeth  203  engage a plurality of clicker teeth  222  disposed at a proximal end of the clicker  220 . As such, when a user dials a dose, these clutch and clicker teeth engage one another to produce a click. Preferably, the clicker teeth  222  are disposed such that each click corresponds to a conventional unit dose, or the like. Therefore, when the dose dial grip  202  and hence the clutch  205  are rotated, an audible sound is heard as the clutch teeth ride  203  over the clicker teeth  222 . 
     The second driver  212  is prevented from rotating since it is splined to the clutch  205 . The clicker  220  comprises a plurality of splines  221   a,  b. These splines  221   a,  b are splined to an inner surface of the inner housing  208 . Therefore, when the Gap a is reduced or closed up, the second driver portion  212  cannot rotate relative to either the housing  204  or the number sleeve  206 . As a consequence, the number sleeve  206  cannot rotate relative to the housing  204 . If the number sleeve  206  is prevented from rotating then, as the spindle  214  is retracted back into the dose setting mechanism  200  and thereby re-set, there will be no risk of the number sleeve  206  being pushed out of the proximal side of the dose setting mechanism  200  as a result of a force being applied on the spindle  214 . 
     Similarly, when the drug delivery device is being dispensed, the user applies an axial load to a dose button  216 . The dose dial grip  202  is rotatably coupled to the dial sleeve and non-rotatably coupled to the dose button  216 . The dose button  216  is axially coupled to the clutch  205  and this prevents relative axial movement. Therefore, the clutch  205  moves axially towards the cartridge end or the distal end of the dose setting mechanism  200 . This movement disengages the clutch  205  from the number sleeve  206 , allowing for relative rotation while closing up the Gap a. 
     As described above, this prevents the clutch  205  from rotating relative to the clicker  220  and hence relative to the housing  204 . However, in this scenario, it also prevents the coupling between the first driver portion  210  and the second driver portion  212  from becoming disengaged. Therefore, any axial load on the spindle  214  only disengages the first and second driver portions  207 ,  212  when the dose button  216  is not axially loaded. This therefore does not happen during dispense. 
     With the dose setting mechanism  200 , as a user dials a dose with the dose dial grip  202 , the metal spring  201  is selected to be strong enough to maintain engagement of both clutched couplings: the clutched coupling between the clutch  205  and the number sleeve  206  and clutched coupling between the first driver portion  207  and second driver portion  212 . 
       FIG.  11    shows in detail of a first arrangement of the first driver portion  207  and the second driver portion  212  illustrated in  FIG.  8   . As illustrated in  FIG.  11   , the second driver portion  212  is generally tubular in shape and comprises at least one drive dog  250  located at a distal end of the second driver portion  212 . The first driver portion  207  also has a generally tubular shape and comprises a plurality of recesses  252  sized to engage with the drive dog  250  on the second driver portion  212 . The construction of the drive dog and recesses allow disengagement with the drive dog  250  when the first and second driver portions are axially pushed together. This construction also creates a rotational coupling when these components are sprung apart. A dose limiter may be provided on first driver portion  207  and operates similarly to the dose limiter  38  illustrated in  FIG.  3   . 
     In this arrangement, the first driver portion  207  comprises a first portion  211  that is permanently clipped to a second portion  210 . In this arrangement, the first portion  211  comprises the drive dogs  252  and the second component  210  includes the outer groove for the last dose nut as well as an internal groove  254 . This internal groove  254  is used to connect to the spindle  214  and drives the spindle  214  during dose administration. 
     In the illustrated arrangement, the internal groove  254  comprises a part helical groove rather than a complete helical groove. One advantage of this arrangement is that it is generally easier to manufacture. 
     As may be seen from the arrangement illustrated in  FIGS.  8 - 10    there is, in addition, certain feature enhancements over the dose setting mechanism  4  lustrated in  FIGS.  3 - 5   . These can be added independently of the ability to re-set the device to replace an empty cartridge with a new cartridge. These enhancements, therefore, are relevant to both a re-settable and non-re-settable dose setting mechanism. 
     One of the advantages of both arrangements illustrated but perhaps in particular in the arrangement illustrated in  FIGS.  8 - 11    is that the dose setting mechanism  200  has a reduced number of components over other known dose setting mechanisms. In addition, apart from the metal coil spring  201  (see  FIGS.  9  and  10   ), all of these components making up the dose setting mechanism  200  may be injection molded using inexpensive and unsophisticated tooling. As just one example, these components making up the dose setting mechanism  200  may be injection molded without the expense and sophistication of a rotating core. 
     Another advantage of a dose setting mechanism  200  comprising an inner housing  208  such as that illustrated in  FIGS.  8 - 11    is that the dose setting mechanism  200  can be designed, with a slight modification, as a drug delivery device platform that is now capable of supporting both re-settable and non-resettable drug delivery devices. As just one example, to modify the re-settable dose setting mechanism  200  variant illustrated in  FIGS.  8 - 11    into a non-resettable drug delivery device, the first driver portion  211  and  210  and the second driver portion  212  can be molded as one unitary part. This reduces the total number of drug delivery device components by two. Otherwise, the drug delivery device illustrated in  FIGS.  8 - 11    could remain unchanged. In such a disposable device, the cartridge holder would be fixed to the housing or alternatively, made as a single one piece body and cartridge holder. 
     The illustration in  FIGS.  8 - 11    shows an inner housing  208  having a length “L”  230  generally similar in overall length to the dose setting mechanism  200  (cf.  FIGS.  12 ,  13   ). As will be described, providing the inner housing  208  with a length of “L” has a number of advantages over other known dose setting mechanisms that do not utilize an inner body or an inner body having a length generally equal to that of the length of a dose setting mechanism. 
     The inner housing  208  comprises a groove  232  provided along an external surface  234  of the inner housing. A groove guide  236  provided on an inner surface  238  of the number sleeve  206  is rotatably engaged with this groove  232 . 
     One advantage of this dose setting mechanism  200  utilizing the inner housing  208  is that the inner housing  208  can be made from an engineering plastic that minimizes friction relative to the number sleeve  206 , groove guide  236  and the groove  232 . For example, one such an engineering plastic could comprise Acetal. However, those of ordinary skill in the art will recognize that other comparable engineering plastics having a low coefficient of friction could also be used. Using such an engineering plastic enables the material for the outer housing  204  to be chosen for aesthetic or tactile reasons with no friction related requirements since the outer housing  204  does not engage any moving components during normal operation. 
     The inner housing  208  also enables the number sleeve  206  to be provided with a helical groove guide  236  on an inner surface  238  of the number sleeve  206 , rather than providing such a helical groove guide on an external surface  240  of the number sleeve  206 . Providing such an internal groove guide results in a number of advantages. For example, this results in the advantage of providing more surface area along the outer surface  240  of number sleeve  206  so as to provide the scale arrangement  242 . More number sleeve surface area may be used for drug or device identification purposes. Another advantage of providing the helical groove  236  on the inner surface  238  of the drive sleeve  206  is that this inner groove  236  is now protected from dirt ingress. In other words, it is more difficult for dirt to become logged in this inner groove interface than if the groove were provided along the outer surface  240  of the number sleeve  206 . This feature is particularly important for a re-settable drug delivery device which will have to function over a much longer period of time compared to a non-resettable device. 
     The effective driving diameter (represented by ‘D’) of the grooved interface between the number sleeve  206  and the inner housing  208  is reduced compared to certain known drug delivery devices for the same outer body diameter. This improves efficiency and enables the drug delivery device to function with a lower pitch (represented by ‘P’) for this groove and groove guide connection. In other words, as the helix angle of the thread determines whether when pushed axially, the number sleeve will rotate or lock to the inner body wherein this helix angle is proportional to the ratio of P/D. 
     The number sleeve  206  can be made the length of the mechanism “L”  230  rather than having to split this length into the space required for the number sleeve  206  and a space required for a clicker and a dose limiter. One advantage of this configuration is that it ensures a good axial engagement between the number sleeve  206  and the outer housing  204 . This improves the functionality (and perceived quality) of the dose setting mechanism when a user uses the drug delivery device to dial out a maximum settable dose.  FIG.  13    illustrates the dose setting mechanism  200  dialed out to a maximum settable dose of 80 International Units (“IU”). 
     Another advantage is that it enables the scale arrangement  242  to be hidden within the outer housing  204  even when the number sleeve  206  is fully dialed out as may be seen from  FIG.  13   . However, the design does not limit the position of the window  14  to that shown in  FIG.  8    but allows this window  14  to be positioned at near the dose dial grip  202  of the device. In arrangements illustrated in  FIGS.  12  and  13   , the scale arrangement  242  will only be visible by way of the window  14 . 
     Also the driver  209  (whether made in two portions or just one unitary component) can be made with a plain internal through hole plus a thread form that can be molded with axially moving core pins. This avoids the disadvantage of a driver having an internal thread with more than one turn and therefore requires a core pin to be rotated out several turns during a de-molding process. 
     One potential disadvantage of utilizing a dose setting mechanism comprising the inner housing  208  is that the use of the inner housing  208  adds a component part to the overall dose setting mechanism  200 . Consequently, this inner housing  208  will tend to increase the overall wall thickness that must be designed to fit between the clutch  205  and number sleeve  206 . One way to work around this design issue, as illustrated in  FIG.  8   , is to reduce the diameter of the clutch  205  and number sleeve  206 . This in turn can be achieved because the thread form between the driver  209  and the spindle  214  comprises a male internal feature on the driver  209  and a female external groove form on the spindle  214  that are overlapping with (on a similar diameter with) the spindle groove form that interfaces with the groove along the inner surface  234  of the inner housing  208  or body portion. 
     The overlapping of groove forms on the spindle  214  reduces the effective diameter of the thread interface with the driver  209 . This also reduces the potential outer diameter of the driver  209  enabling the addition of the inner housing  208  without increasing the overall outer diameter of the dose setting mechanism  200 . Another added benefit of the reduced effective diameter of the thread interface with the driver  209  is that it improves efficiency of the drug delivery device during dispense as explained above. 
     The window  244  through which the scale arrangement  242  may be viewed can either be just an aperture in the outer housing  204  or can include a clear lens or window designed to magnify the scale arrangement (i.e., printed or laser marked dose numbers) along a portion of the outer surface  240  on the number sleeve  206 . 
     The connection of a cartridge holder into the outer housing  204  can be achieved using either a screw or bayonet type connection. Alternatively, any similarly robust design used in drug delivery devices requiring a largely cylindrical part to be removed and then reattached could also be used. 
     Exemplary embodiments of the present invention have been described. Those skilled in the art will understand, however, that changes and modifications may be made to these embodiments without departing from the true scope and spirit of the present invention, which is defined by the claims.