WO2011092536A1

WO2011092536A1 - Drug cartrigde different inner surface conditions

Info

Publication number: WO2011092536A1
Application number: PCT/IB2010/000609
Authority: WO
Inventors: Thomas Ballet; Franz Bruckert
Original assignee: Becton Dickinson France
Priority date: 2010-01-26
Filing date: 2010-01-26
Publication date: 2011-08-04

Abstract

Barrel of a drug holding component for a drug delivery system, barrel comprising an hollow elongated body (2) forming a chamber (3) and having opposed distal (4) and proximal (5) ends; at the distal end (4), a delivery port (6); at the proximal end (5), a filling opening (7) adapted for the introduction of a piston (15) within the chamber (3); wherein the chamber (3) comprises at least one distal portion (3D) intended to form at least one drug compartment (D) which extends from the delivery port (6) towards an intermediate area (I) of the chamber (3) and a proximal portion (3F) intended to form a propelling fluid compartment (F) which extends from the intermediate area (I) to the filling opening (7), the distal (3D) and proximal (3F) portions having different inner surface conditions.

Description

DRUG CARTRIGDE DIFFERENT INNER SURFACE CONDITIONS

TECHNICAL FIELD

[0001 ] The invention generally relates to drug holding components of drug delivery systems implementing an injection like process for delivering a drug or drug formulation directly to a patient or trough a fluid administration circuit. In some none exclusive implementation, the invention relates to pre-fillable and pre-filled components of such drug delivery systems.

BACKGROUND ART

[0002] Many drug delivery systems, like syringes, pre-filled syringes, drug cartridge and needless injectors include an internal chamber for receiving a medicament and a piston. The piston is usually slidable within the interior chamber and in a fluid tight relationship with a wall from the interior chamber. The piston can take many forms with two conventional forms being a body made of rubber or elastomeric material and a hard plastic body provided with an O-ring also made of rubber or elastomeric material. The Interior chamber of such drug delivery systems is generally made of plastic or glass. The fluid tight relationship between the filling member and the wall from the interior chamber provides a large resistance to movement of the piston within the interior chamber. Typically, the resistance can be reduced by pre-treating the wall of the interior chamber with a silicone oil or emulsion such as disclosed in US 2007/0186510.

[0003] The siliconization of the inner wall of the chamber allows a smooth movement or gliding of the piston within the chamber but it as been found that in some cases the silicone of the coating may interact with some of the components of the drug or medicament and alter the drug properties.

[0004] Therefore an object of this invention is to substantially reduce if not override the risk of any destructive interaction between the drug components and inner walls of the drug holding chamber of pre-filled drug delivery systems. SUMMARY OF THE INVENTION

[0005] In order to achieve this, the invention concerns a drug holding component for conservation and delivery of at least a drug, comprising;

- a barrel which comprises :

- an hollow elongated body forming a chamber and having opposed distal and proximal ends;

- at the distal end, a delivery port;

- at the proximal end, a filling opening;

- a piston sealing the filing opening and being adapted for sliding inside the chamber;

- an intermediate stopper which delimits in the chamber, on one side towards the distal end, at least one drug compartment and containing the drug and, on the other side, a fluid compartment extending up to the piston and containing a propelling fluid;

the intermediate stopper and/or the barrel being adapted for:

- stopping any drug flow or leakage from the drug compartment to the fluid compartment;

- allowing the propelling fluid to flow in the drug compartment for expelling the drug through the del ivery port when the piston is pushed towards the intermediate stopper.

[0006] By definition, the drug is in a liquid form.

[0007] By insulating the drug from the piston and the region where it slides, the invention prevents any risk of interaction between the drug or medicament and the gliding or sliding agent which might be used for facilitating the movement of the piston. Furthermore by separating the two compartments it is possible to implement for each compartment surface conditions addressing different objectives even contradictory or incompatible objectives with out any risk of damage of the content of the drug holding component. Therefore when designing the drug holding component it is possible to focus for each compartment on its specific function without having to take into consideration the function and the design of the other compartment. This is a great advantage when the first compartment is for example designed for drug stability as the factors which might affect the drug formulation stability or the drug components properties, are numerous. So by avoiding having to take into consideration for designing the first compartment also sliding conditions which would have otherwise brought in numerous other factors, the invention simplifies the whole design process of the drug holding component.

[0008] The propelling fluid may be of any type, liquid or gas, as long as it does not mix with the drug or dilute the drug. According to an aspect of the invention, the propelling fluid is a gas and preferably a gas which will not react with the drug. According to a further aspect of the invention, the propelling fluid is an inert gas such as for example Nitrogen or Argon.

[0009] According to an embodiment of the invention the drug holding component or the drug delivery device incorporating the drug holding component is adapted to prevent any ejection of the propelling fluid during the injection process. This can be achieved in various ways. First, according to an embodiment, the two chambers have the same volume.

[0010] Second, when the drug holding component forms the body of a pre- filled syringe, the length of a punching rod used for pushing the piston can be chosen long enough to transfer propelling fluid in the drug compartment but too short for moving the intermediate stopper. Is this case there is no need for the intermediate to be affixed to the barrel. According to an embodiment, the two chambers have the same volume.

[0011] Third, the prevention of any ejection of propelling fluid can also be achieved differently. For example the intermediate stopper can affixed to the barrel or immobilised in the barrel, so that it will stop the piston once the fluid chamber is empty. According to an aspect of the invention, the intermediate stopper is glued to the inner wall of the chamber. According to another aspect of the invention, the body or barrel comprises holding means for the intermediate stopper. According to an embodiment, the two chambers have the same volume.

[0012] According to a feature of the invention, the intermediate stopper is adapted for stopping any fluid flow between the drug and fluid compartments when the piston is not actuated. According to an embodiment, the pressure inside the fluid compartment equals the pressure inside the drug compartment and the intermediate stopper is adapted for stopping any fluid flow between the drug and fluid compartments. [0013] According to the invention, the stopper is adapted to allow the flow of the propelling fluid from the fluid compartment to the drug compartment. This can be achieved in various ways.

[0014] In an embodiment, the stopper comprises a thin elastomeric membrane provided with one or several cuts, acting as septum(s). For example, the membrane has a central cut acting as a septum.

[0015] In another embodiment, the stopper comprises at least one non-return valve oriented to allow a flow only from the fluid compartment into the drug compartment.

[0016] The invention concerns also a barrel adapted to form, in association with at least an intermediate stopper and a piston, a drug holding component according to the invention. Therefore the invention concerns a barrel of a drug holding component for a drug delivery system, barrel comprising :

- at the distal end, a delivery port;

- at the proximal end, a filling opening adapted for the introduction of a piston within the chamber.

According to the invention, the chamber comprises:

- at least one distal portion intended to form at least one drug compartment which extends from the delivery port towards an intermediate area of the chamber;

- and a proximal portion intended to form a propelling fluid compartment which extends from the intermediate area to the filling opening;

the first and proximal portions having different inner surface conditions.

[0017] According to a feature, the two chambers have the same volume.

[0018] According to a particular embodiment, the drug holding component or the barrel comprises two drug compartments separated by a slidable or free piston. Accord ing to a featu re, the cu mulated volu me of the two drugs compartments equal the volume of the propelling fluid compartment. In an embodiment there is more than two, e.g. three drug compartments and more than one, e.g. two slidable or free pistons, an the volumes preferably follow the mentioned rule. [0019] According to a feature in a barrel or drug holding component having at least two drug compartments, there is a distal drug compartment located at the distal end and a second compartment separated from the distal one by the free piston, the distal compartment is connected to the delivery port for expelling the drug from the distal compartment, wherein the distal compartment comprises further a by-pass connecting the distal drug compartment to the delivery port when the free piston abuts the distal end. Therefore, when the free piston abuts the distal end after the distal drug compartment is emptied, the drug in the second compartment may be expelled through the by-pass and the delivery port.

[0020] In the context of the invention, the wording "the distal and proximal portion having different inner surface conditions" means that the inner surfaces of the distal portion have different physical and/or chemical properties than the inner surface of the proximal portion, the inner surface of each portion being coated or not. In this meaning, when the inner surfaces of the proximal portion and the distal portion are made from the same material and are not coated, they may have different surface roughness which corresponds to different surface conditions according to the invention.

[0021] As stated before the surface conditions of the distal and proximal portions may address different objectives even contradictory or incompatible objectives. According to an embodiment, the inner surfaces of each surface are both coated and the coatings are different.

[0022] According to an aspect of the invention, the inner surface of the distal portion of the barrel has surface conditions optimized for drug or drug formulation stability. For example the inner surface of the distal portion is designed to have one, several or all the following properties :

- being non-ionic;

- providing steric-hindrance;

- being hydrophilic;

- being H-bond accepting.

[0023] According to an aspect of the invention, the inner surface of the distal portion or the distal portion is made of borosilicate.

[0024] According to an aspect of the invention, the inner surface of the distal portion of the barrel is coated with a coating suited to the stability of the drug. Depending on the drug which is contained, the person skilled in the art may select the coating suited to the drug.

[0025] According to an embodiment, the inner surface of the distal portion of the barrel is coated with a S1O2 layer.

[0026] According to an embodiment, the inner surface of the distal portion of the barrel is coated with an hydrophilic coating. According to a feature, the hydrophilic coating comprises an hydrophilic polymer.

[0027] This hydrophilic polymer may be chosen from the group consisting of:

- poly(N-vinyl lactams) such as poly(vinylpyrrolidone),

- polyethylene oxide,

- polypropylene oxide,

- polyacrylamide,

- cellulosics such as methyl cellulose and the like,

- polyacrylic acids such as acrylic and methacrylic acids and the like,

- polyvinyl alcohols,

- polyvinylethers and the like,

- polysaccharides such as hyaluronic acid polymers,

- polyaminoacids, including a single aminoacid or a mixture of different, at least two, polyaminoacids,

- zwitterion polymers,

- phosphorylcholine containing compounds,

- polyethyleneglycol alone or in a mixture with polyurethane,

- acrylic or vinyl polymers,

- or a mixture of at least two of them, and any of these materials being optionally substituted.

[0028] The polymer may be moisturized by a polar solvent, as described thereafter.

[0029] The inner surface of the distal portion may be pre-coated or not before applying the hydrophilic coating. In an embodiment, the inner surface of the distal portion is pre-coated with an hydrophobic coating in order to have a barrier effect. Such coating may be chosen amongst the fluoropolymers (in particular PTFE, PFPE), parylene, polyorganosiloxanes such as PDMS (polydimethylsiloxane). [0030] According to an aspect of the invention, the hydrophilic polymer is crosslinkable. According an aspect of the invention, the viscosity of the polymer depends of the nature and the degree of crosslinking.

[0031] According to an aspect of the invention, the hydrophilic polymer is not crosslinkable but it is mixed with a supporting polymer which is crosslinkable.

[0032] According to an aspect of the invention, the hydrophilic polymer is crosslinkable and is mixed with a supporting polymer which is crosslinkable too.

[0033] The invention provides for embodiments where there are at least two drug compartments. In this case, there is at least one free or slidable piston between compartments. Then the inner surface of the distal drug compartment and more generally of any inner surface of drug compartment along which the piston may slide, has surface conditions optimized for gliding whereas the surface condition have also to be suited for drug stability.

[0034] In an embodiment, this inner surface is coated with the hydrophilic coating, preferably an hydrophilic polymer as described above. In order to confer good gliding properties, the hydrophilic coating is moisturized by a polar solvent.

[0035] According to the invention the polar solvent is chosen in the group of water or alcohol such as ethanol, methanol, propanol, isopropanol and the like.

[0036] In a preferred embodiment the polar solvent is water.

[0037] According to an aspect of the invention, the inner surface of the proximal portion is coated. The inner surface of the proximal portion is, for example but not necessarily, coated with a coating comprising at least one constituent of the following list :

- silicone oil;

- baked silicone;

- CVD polysiloxane

- plasma-treated silicone,

- fluoric coating.

[0038] Accord ing to an aspect of the invention , the inner surface of the proximal portion has surface conditions optimized for gliding. Such surface conditions enable a smooth sliding of the piston within the second chamber when the barrel is incorporated in a drug delivery device such as a pre-filled syringe for example. [0039] According to an aspect of the invention the proximal portion is designed to be non-hydrophilic. In an embodiment, it is coated with a non-hydrophilic coating.

[0040] According to the invention, the barrel of the drug holding component can be made of any appropriate material such as glass or plastic.

[0041] According to an aspect of the invention, the plastic is propylene or cyclopolyolefin (CCP).

[0042] According to an aspect of the invention, the glass is borosilicate.

[0043] According to an aspect of the invention the stopper can be made of rubber or elastomeric material .

[0044] According to an aspect of the invention, the drug holding component is an injection syringe. According to a feature, the delivery port may be provided with an injection needle removable or not.

[0045] The coating compositions may be applied to the articles, barrel and stopper using conventional techniques, such as dip coating (immersion in a bath), spray coating and the like.

[0046] Typically the coatings have an average thickness smaller than 2 nm.

[0047] The coating could be dried to provide a dry coating by standing at ambient temperature or by heating at temperature between 30 to 100 Ό.

[0048] The coating may be further crosslinked during or after the drying step.

[0049] The crosslink reaction may be done from the functional groups of the polymer without the need of a crosslinking agent.

[0050] In other embodiments the crosslink reaction is initiated by addition of a crosslink agent to the coating composition.

[0051] According to one embodiment the moisturizing step is a step of applying by any means a polar solvent on the coated surface.

[0052] In one embodiment the application of the polar solvent is done by spraying or by immersing the articles, the barrel and/or the stopper in a bath or by providing a wet atmosphere.

[0053] The various above aspects, features, embodiments or objects of the invention may be combined in various ways with each others provided the combined aspects, features, embodiments or objects are not incompatible or mutually exclusive. [0054] Further aspects and advantages of the present invention will be apparent from the following detailed description made in conjunction with the accompanying drawing illustrating schematically some non-limitative embodiments of the invention.

DESCRIPTION OF THE FIGURES

[0055] Fig. 1 is a schematic longitudinal section of a drug delivery device, here a syringe, incorporating a drug holding component according to the invention.

[0056] Fig. 2 is a schematic longitudinal section of a barrel being a part of the drug holding component illustrated on Fig. 1 .

[0057] Fig.3 is a schematic longitudinal section of the drug delivery device of Fig. 1 after use.

[0058] Fig. 4 is a schematic longitudinal section of the barrel illustrated on Fig.

2 after its filling with drug and placement of an intermediate stopper.

[0059] Fig. 5 is a schematic longitudinal section of the drug holding component shown Fig. 1 and formed with the filled barrel of Fig. 4 closed with a piston.

[0060] Fig. 6 is a schematic longitudinal section of a barrel being a part of another embodiment of a drug holding component according to the invention.

[0061] Fig. 7 is a schematic longitudinal section of a drug holding component incorporating the barrel illustrated on Fig. 6.

[0062] Fig. 8 to Fig.10 are schematic longitudinal sections of a barrel and a drug holding component incorporating this barrel, showing some steps of a possible fabrication process.

[0063] Fig. 1 1 and Fig. 12 are each a schematic longitudinal section of a barrel being a part of another embodiment of a drug holding component according to the invention.

[0064] Fig. 13 is a schematic longitudinal section of another embodiment of a drug delivery device, according to the invention, comprising in its proximal region a fluid compartment and in its distal region two separated drug compartments.

[0065] Fig. 14 is a schematic longitudinal section of the drug delivery device of Fig. 13 after use.

[0066] Fig. 15 is a schematic longitudinal section of the barrel being a part of the drug holding component illustrated on Fig. 13 and Fig. 14. [0067] Corresponding reference numbers indicate corresponding components in the various embodiments illustrated in the Figures.

DESCRIPTION OF THE INVENTION

[0068] The drug holding component according to the invention, as illustrated on Fig. 1 and designated as a whole by reference number 1 , is designed to form a part of a drug delivery system or the drug delivery system itself. On the shown example the drug holding component 1 constitutes an injection syringe.

[0069] The drug holding component 1 comprises a barrel 2 shown on its own on Fig. 2. The barrel 2 is formed by a hollow elongated body defining a chamber 3 and having opposed distal 4 and proximal 5 ends. The distal end 4 comprises a delivery port 6 with a passage way of a smaller cross-section than the chamber 3. The proximal end 5 comprises a filling opening with a same cross-section as a proximal part of the chamber 3. As the drug holding component 1 is, on the shown example, intended to form a syringe body, the barrel 2 comprises at its proximal end 5 a peripheral flange 8. Holding component 1 further comprises an intermediate stopper 10 which delimits in the chamber a drug compartment D and a propelling fluid compartment F. The drug compartment D extends from the intermediate stopper 10 up to the distal end 4 whereas the fluid compartment F extends from the intermediate stopper 10 up to the proximal end 5. The fluid compartment F is further closed by a piston 15 which is in a fluid tight relationship with the inner wall of the chamber 3. As it will be described later, the piston 15 is adapted to slide within the fluid chamber F. The piston 15 comprises a housing 17 for receiving an extremity of a plunger rod 18. The chambers so delimited have the same volume.

[0070] In a ready-to-use state as illustrated on Fig. 1 , the drug compartment D is filled with some drug or drug formulation and the fluid compartment is filled with a propelling fluid preferably but not necessarily an inert gas such as Nitrogen. It can be noted that on the shown example the delivery port 6 is further closed with a removable tip cap 20. When the drug contained in the drug compartment D must be injected to a patient, the plunger rod 18 is fitted in the housing 17 then the tip cap 20 is removed and replaced by a removable needle 21 . After this the needle is engaged in an infusion circuit or in the patient body and the operator presses on the plunger rod 18 so that the piston slides within the fluid chamber F. The intermediate stopper 10 is therefore designed to allow the transfer of the propelling fluid from the fluid compartment F into the drug compartment D. As the propelling fluid is chosen in order not to mix with the drug, the propelling fluid will transmit the pressure from the piston to the drug which will be ejected through the delivery port 6 and the needle 21 . The sliding of the piston 15 is pursued until the drug compartment D is empty of drug and full of propelling fluid as shown on Fig. 3.

[0071] The drug holding component 1 may be designed in order to prevent any accidental injection of propelling fluid to the patient. In order to achieve this, the intermediate stopper 10 may be fixed to the barrel 2. So at the end of the injection process, the piston movement will be stopped by the intermediate stopper 10. This can also be achieved by any other appropriate means as for example by designing the plunger rod 18 so that its length corresponds exactly to the length of the translation needed for ejecting all the drug from the drug compartment D. It can also be done by providing the plunger rod 18, having a length superior to the length of the needed translation, with a stop which will restrain the translation abutting the body.

[0072] One function of the intermediate stopper 10 is thus to allow the flow of the propelling fluid from the fluid compartment F to the drug compartment D. Another function of the intermediate stopper 10 is to prevent, before use of the drug holding component 1 and during its storage, any flow or leakage of drug from the drug compartment D into the fluid compartment F. This can be achieved in various ways. For example, on the shown embodiment the intermediate stopper 10 comprises a thin elastomeric membrane 30 provided with a central cut 31 . The cut membrane 30 acts as a septum. When the difference between pressure within the drug compartment D and the pressure within the fluid compartment F is null or sensibly null, the membrane blocks any fluid flow in either direction. When the pressure in the fluid compartment F is higher than the pressure in the drug compartment D which occurs when the piston 15 is pushed, the cut 31 opens, allowing the propelling fluid to flow into the drug compartment. This function of the intermediate stopper can also be achieved by incorporating in the intermediate stopper a non-return valve oriented to allow a flow only from the fluid compartment F into the drug compartment D.

[0073] It has been understood from the above description that the drug compartment D and the fluid compartment F have different functions. The main function of the drug compartment is to hold a drug or a drug formulation and to prevent any modification and contamination of the drug, while the main function of the fluid compartment is to hold the propelling fluid and to allow a smooth sliding of the piston within the chamber so that to allow injection of small amounts of drug as well as a slow continuous injection of drug.

[0074] These two types of function may imply different if not incompatible surface conditions for the drug compartment D and the fluid compartment F. For example a smooth sliding of the piston can be achieved through the use of silicon oil which is known for interacting with many drugs.

[0075] Therefore, the invention proposes to implement the barrel as shown on Fig. 2. According to the invention, the chamber 3 of the barrel 2 comprises a distal portion 3D intended to form the drug compartment D and a proximal portion 3_F intended to form the propelling fluid compartment F. The distal portion 3_D extends from the delivery port 6 to an intermediate area I (see Fig.1 ) of the chamber whereas the proximal portion 3_F extends from the intermediate area I to the filling opening 7. The wall of the distal portion 3D and the proximal portion 3F have different surface conditions which are depicted with dashes for the distal portion 3D and with crosses for the proximal portion 3F. The differences of surface conditions may result of different coating on the inner wall of the first and proximal portions, or of different materials used for making the inner wall of the distal portion 3_D and the proximal portion 3_F as well as of different combination of different materials and/or coatings.

On the shown example, the differences of surface conditions between the distal portion 3D and the proximal portion 3F result of different coatings applied on the inner surface of respectively the distal portion 3D and the proximal portion 3F. In this case, the inner surface of the distal portion is designed and coated in order to enhance drug stability. Such stabilizing properties of the inner surface of the distal portion 3D may be achieved by using a coating suitable for drug stability. The person skilled in the art is able to select a coating suited to the very drug that is to be contained in the barrel. For example, the coating is a hydrophilic coating and in particular is chosen among one of the hydrophilic coatings described above.

[0076] Such stabilizing surface conditions of the distal portion 3D may be also achieved by using a suitable glass material for the inner wall of the distal portion.

[0077] In the shown example the proximal portion 3_F is coated with materials induce good sliding conditions for the piston.

[0078] For example, the inner wall of the proximal portion 3F is coated with silicone oil, baked silicone, CVD polysiloxane, plasma-treated silicone, fluoric coating.

[0079] It should be noted that the intermediate area I is not necessarily defined by a clear boundary between the coating of the distal portion 3_D and the coating of the proximal portion 3F but can also be formed by a smooth transition between the coating of the distal portion 3D and the coating of the proximal portion 3F.

[0080] It should be also noted that if a coating is used for the distal portion 3_D then this coating may be applied so that to extend inside the passage way of the delivery port 6.

[0081] Once the barrel 2 is manufactured it can be provided with the tip cap 20 sealing the delivery port 6. Then the barrel may be packed before being delivered to a filling unit.

[0082] In the filling unit, after unpacking, the barrel 2 will be filled with some drug or drug formulation up to a level near to the intermediate area. Then after filling, the intermediate stopper 10 is pushed through the filling opening 7 down to the intermediate area I. In the shown embodiment the elastomeric thin wall 30 and the cut 31 allow the gas caught between the intermediate stopper and the drug upper level to escape through the cut 31 during the sliding of the intermediate stopper 10. Once the intermediate stopper 10 is in the intermediate area I, as shown on Fig. 4, the stopper 10 can be affixed to the barrel using for example an appropriate adhesive. After that, the piston is introduced in the barrel so as to seal the barrel. This filling operation can be conducted in an inert gas atmosphere so that the gas caught in the fluid compartment is an inert gas. Once this filling operation conducted, the drug holding component 1 is in a ready-to- use state as shown Fig. 5. [0083] The immobilization of the intermediate stopper 10 in the intermediate area I is not necessarily achieved by using adhesive. On the shown example of Fig. 6 and 7, the immobilization of the intermediate stopper 10 is achieved by holding means 35 provided on the inner wall of the chamber 3 in the intermediate area I. Furthermore in this example, the intermediate stopper differs from the one disclosed illustrated Fig. 1 to 5 in that it is made of a porous material stopping liquids and/or molecules and allowing only gas to pass through.

[0084] Fig. 8 to 10 illustrate a different way for manufacturing the drug holding component 1 and the barrel 2 than the one exposed in relation with Fig. 1 to 5. According to this other manufacturing process, the distal portion 3D is coated and the tip cap 20 is fitted on the delivery port 6. Then the drug compartment is filled with drug up to the intermediate level I. After this filling, the intermediate stopper 10 is introduced in order to close the drug compartment D. At this stage, the drug holding component 1 is in the condition shown on Fig. 9. Then the inner wall of the distal portion 3_D is coated with a sliding coating. Once the coating is done, the fluid compartment F is closed by the piston 15 as shown on Fig. 10.

[0085] Fig. 1 1 illustrates another embodiment of the barrel 2 which differs from the embodiment previously described in that only the proximal portion 3_F of the inner wall of the chamber 3 is coated whereas the distal portion of the inner wall of the chamber is not coated. Fig. 12 illustrates a barrel designed the other way around the distal portion 3D of the chamber 3 being coated and the proximal portion 3F being not coated.

[0086] Fig .1 3 to 1 5 illustrate a still another embodiment of a drug holding component 1 according to the invention designed for a sequential delivery of two different drugs.

[0087] As shown by Fig. 13, the drug holding component 1 comprises a fluid compartment 3F and two drug compartments 3DI , 3D2 separated by a free piston 25, the fluid compartment 3F being separated from the second drug compartment 3D2 by the stopper 10. The free piston 25 is designed for sliding within the first drug compartment 3_Di - The barrel 2 forming the drug holding component further com prises, at its d istal end 4 , a by-pass 26 con n ecting the first drug compartment 3DI to the delivery port 6. [0088] In a ready-to-use state as shown on Fig. 1 3, the first 3DI and second 3D2 drug compartments are filled with two different drugs whereas the fluid compartment 3_F is filled with a propelling fluid. When a delivery of the drugs is needed, the plunger rod 18 is pressed so that the piston 15 slides within the fluid chamber 3_F transferring the flu id in the second drug compartment 3_D2 as previously described. The drug within the second compartment 3_D2 will transmit the pressure to the free piston 25 which will slide expelling the first drug through the delivery port 6 out from the delivery holding component. When the free piston 25 reaches the distal end 4 as shown on Fig. 14, the first drug compartment 3_Di is emptied and the second drug previously hold by the second compartment 3D2 flows, through the by-pass 26 and the port 6, out from the holding component 1 . This sequential delivery of the two drugs is completed when the piston 15 reaches the stopper 10 as shown on Fig.14.

[0089] As the drug compartments are separated it is possible to design each compartment for a good conservation of drugs requiring different conservation conditions. For this purpose the walls of two drug compartments may have different surface conditions. For example, the inner surface of the first drug compartment 3_Di is designed for allowing a smooth gliding of the free piston 25 whereas the surface of the second drug compartment 3_D2 is designed for drug stability

[0090] Therefore the barrel 2, shown on Fig . 1 5, forming the drug holding component 1 has three portions, the proximal portion 3F, a first distal portion 3DI next to the distal end 4 and a second distal portion 3D2 between the proximal portion 3_F and the first distal portion 3_Di - The proximal portion 3_F will have surface conditions enhancing gliding such as for example a silicone oil coating. The first distal portion 3DI will have for example a fluoric coating such coating being known for enhancing gliding with low interaction risk with drug and the second distal portion 3D2 will be, for example, made of raw glass with no coating at all, as raw glass is known for interacting with very few drugs. As an alternative, the inner surface of the first drug compartment 3_Di is coated with an hydrophilic coating which is further moisturized in order to provide for smooth gliding.

[0091] According to this example, the barrel 2 have three portions 3_F, 3DI, 3D2 each with different surface conditions than the two others but it should understood that according to the invention other combinations are possible. For example, one portion may have different surface conditions than the two others these having the same surface conditions. It should be also understood that the barrel may have more than three portions with different surface conditions as wel l as th e d ru g hol d i ng com pon e nt m ay h ave more than two drug compartments.

[0092] While the invention has been shown and described with reference to certain embodiments thereof, it would be understood by those skilled in the art that changes in form and details may be made therein without departing from the spirit and scope of the invention as defined in the appended claims

Claims

1 . Barrel of a d rug hold ing com ponent for a d rug delivery system, barrel comprising :

- an hollow elongated body (2) forming a chamber (3) and having opposed distal (4) and proximal (5) ends;

- at the distal end (4), a delivery port (6);

- at the proximal end (5), a filling opening (7) adapted for the introduction of a piston (15) within the chamber (3);

wherein the chamber (3) comprises:

- at l east one d istal portion (3D) intended to form at least one drug compartment (D) which extends from the delivery port (6) towards an intermediate area (I) of the chamber (3);

- and a proximal portion (3F) intended to form a propelling fluid compartment (F) which extends from the intermediate area (I) to the filling opening (7);

the distal (3_D) and proximal (3_F) portions having d ifferent inner surface conditions.

2. Barrel of a drug holding component according to claim 1 , wherein the drug compartment (D) and the propelling fluid compartment (F) have the same volume.

3. Barrel of a drug holding component according to claim 1 or 2, wherein the inner surface of the distal portion (3_D) is coated.

4. Barrel of a drug holding component according to any one of claims 1 to 3, wherein the inner surface of the distal portion (3D) has surface conditions optimized for drug or drug formulation stability.

5. Barrel of a drug holding component according to any of claims 1 to 4, wherein the inner surface of the distal portion (3_D) is coated with an hydrophilic coating.

6. Barrel of a drug holding component according to claim 5, wherein the hydrophilic coating comprises an hydrophilic polymer.

7. Barrel of a drug holding component according to claim 6, wherein the hydrophilic polymer is chosen among the group consisting of substituted or not substituted poly(N-vinyl lactams), polyethylene oxide, polypropylene oxide, polyacrylamide, cellulosics, polyacrylic acids, polyvinyl alcohols, polyvinylethers, polysaccharides, polyaminoacids, zwitterion polymers, phosphorylcholine containing com pou nds , polyethylen eg lycol alon e or in a mixture with polyurethane, acrylic or vinyl polymers, and mixtures thereof.

8. Barrel of a drug holding component according to claim 6, wherein the hydrophilic polymer is chosen among the group consisting of substituted or not substituted poly(vinylpyrrolidone), methyl cellulose, acrylic acids, methacrylic acids, hyaluronic acid polymers, and mixtures thereof.

9. Barrel of a drug holding component according to any of claims 1 to 8, wherein the inner surface of the proximal portion (3F) is coated.

1 0. Barrel of a drug holding component according to any of claims 1 to 9, wherein the inner surface of the proximal portion (3F) has surface conditions optimized for gliding.

1 1 . Barrel of a drug holding component according to any of claims 1 to 1 0, wherein the inner surface of the proximal portion (3_F) is coated with a coating comprising at least one constituent of the following list :

- silicone oil;

- baked silicone;

- CVD polysiloxane;

- plasma-treated silicone;

- fluoric coating.

12. Barrel of a drug holding component according to any of claims 1 to 1 1 , wherein the barrel (2) is made of glass.

13. Barrel of a drug holding component according to any of claims 1 to 1 1 , wherein the barrel (2) is made of plastic.

14. Barrel of a drug holding component according to any of claims 1 to 1 3, wherein the chamber (3) comprises, in the intermediate area, holding means (35) for an intermediate stopper.

15. Barrel of a drug holding component according to any of claims 1 to 1 4, wherein the delivery port (6) is provided with an injection needle (21 ).

16. Barrel of a drug holding component according to any of claims 1 to 1 5, wherein it comprises a distal drug compartment (3DI ) and a second drug compartment (3D2) separated from the fluid compartment by the stopper (10), and wherein both drug compartments are separated by a free piston (25).

17. Barrel of a drug holding component according to claim 16wherein the distal drug compartment (3_Di ) is connected to the delivery port (6) for expelling the drug from the distal drug compartment, and wherein the distal compartment (3_Di ) comprises further a by-pass connecting the distal drug compartment to the delivery port when the free piston (25) abuts the distal end.

18. Barrel of a drug holding component according to claim 16 or 17, wherein the drug compartment (3DI ) has a coating with an hydrophilic polymer which is moisturized using a polar solvent.

19. Drug holding component for conservation and delivery of at least a drug, comprising;

- a barrel which comprises :

- at the distal end (4), a delivery port (6);

- at the proximal end (5), a filling opening (7);

- a piston (15) sealing the filing opening (7) and being adapted for sliding inside the chamber (3),

- an intermediate stopper (10) which delimits in the chamber (3), on one side towards the distal end (4), at least one drug compartment (D) containing the drug and, on the other side, a fluid compartment (F) extending up to the piston (15) and containing a propelling fluid, the intermediate stopper (10) and/or the barrel (2) being adapted for:

- stopping any drug flow or leakage from the drug compartment (D) to the fluid compartment (F);

- allowing the propelling fluid to flow in the drug compartment (D) for expelling the drug through the delivery port (6) when the piston (15) is pushed towards the intermediate stopper (10).

20. Drug hold ing com pon ent accord ing to cla i m 1 9, wherein the drug compartment (D) and the propelling fluid compartment (F) have the same volume.

21 . Drug holding component according to claim 19 or 20, wherein the propelling fluid is a gas.

22. Drug holding component according to claim 21 , wherein the propelling fluid is an inert gas.

23. Drug holding component according to any of claims 1 9 to 23, wherein the intermediate stopper (10) is affixed to the barrel (2).

24. Drug holding component according to any of claims 1 9 to 23, wherein the intermediate stopper (10) is adapted for allowing the propelling fluid to flow from the fluid compartment (F) to the drug compartment (D).

25. Drug holding component according to any of claims 1 9 to 24, wherein the intermediate stopper (10) is adapted for stopping any fluid flow between to the drug and fluid compartments when the pressure inside the fluid compartment (F) equals the pressure inside the drug compartment (D).

26. Drug holding component according to any of claims 1 9 to 25, wherein the intermediate stopper (10) is an elastomeric membrane acting as a septum or comprises a non-return valve.

27. Drug holding component according to any of claims 1 9 to 26, wherein it comprises a distal drug compartment (3_Di ) and a second drug compartment (3_D2) separated from the fluid compartment by the stopper (10), and wherein both drug compartments are separated by a free piston (25).

28. Drug hold ing com pon ent accord ing to cla i m 27, wherein the drug compartment (3DI) has a coating with an hydrophilic polymer which is moisturized using a polar solvent.

29. Drug holding component according to claim 27 or 28, wherein the drug compartment (3_D2) has a coating with an hydrophilic polymer.

30. Drug holding component according to any of claims 19 to 29, comprising a barrel (2) according to any of claims 1 to 18 which distal portion (3D) forms the drug compartment (D) and proximal portion (3F) forms the fluid compartment (F).