Abstract:
A method and apparatus are described for making an article such as the body of a needleless injector capsule, from a formable material, such as glass, the article having a cavity communicating with the exterior via an orifice. A blank having an open end is mounted on a first forming tool, and the open end is engaged by a second forming tool while an end region of the blank adjacent the open end is in a condition to permit it to be formed. One of the tools has a pin extending therefrom, and when the tools are brought together to form the end region into the desired shape the pin defines the orifice.

Description:
This is a continuation, of application Ser. No. 09/285,190, filed Mar. 24, 1999 now U.S. Pat. No. 6,216,493, which application was a continuation of International Application No. PCT/GB/97/02560, filed Sep. 22, 1997 (now expired). Each of these prior applications is hereby incorporated herein by reference, in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The invention is in the field of needleless injectors which use a capsule for containing a liquid drug to be injected, and needle-type hypodermic syringe bodies. 
     BACKGROUND OF THE INVENTION 
     Needleless injectors are used as an alternative to conventional hypodermic injectors to deliver medicaments through the patient&#39;s skin into the underlying tissues. Such injectors use a high pressure piston pump to dispense a jet of liquid drug with sufficient force to penetrate the skin, and thereafter deposit the drug into the dermal. subcutaneous or muscular tissues. 
     The drug is dispensed from a cylindrical chamber, having a fine orifice at one end through which the drug is discharged. A piston is slidingly and sealingly located in the chamber, and the drug is contained within the space between the orifice and piston. To make an injection, the orifice is placed on the skin, and by operating a release mechanism, the piston is acted upon by a force which may be derived from a spring, pressurised gas or chemical reaction. 
     The capsule may be filled by the user, or may be prefilled and pre-assembled to an actuator. In the latter case particularly, the materials from which the capsule and piston are constructed must be inert to the drug—i.e. they must not react with the drug chemically, nor physically, and must not contain harmful extractives that might contaminate the drug. The choice of materials is small: borosilicate glass is the most favoured capsule material when drugs must be stored for more than a few hours. If an alternative material is selected for the capsule, years of testing must be done to validate that material, whereas borosilicate glass has a known compatibility with most drugs. 
     During the injection, the pressure generated in the capsule is at least 100 bars, and it is preferable, in order to avoid leakage during injection, that the orifice is integral with the cylindrical chamber. Furthermore, the form and dimension of the orifice is critical to the injection performance, and for repeatable results these features should be made to close tolerances. However, glass is a difficult material to mould and maintain such close tolerances over many millions of components. One traditional method is to work the heated and softened end of a glass tube on a lathe, and by applying a shaping wheel or paddle, to close up one end onto a mandrel to form the orifice. This is a relatively crude method, and the only parameters that may be controlled accurately are the orifice diameter and the diameter of the surrounding glass: the length and entry profile of the orifice are left to chance because the process shapes only the outside of the tube and the orifice diameter. An alternative process is moulding, whereby a hot “gob” of molten glass is moulded in a die. This process is suitable for large components, but needleless injector capsules are seldom larger than 1 ml capacity, and such a small gob of glass loses its heat rapidly and is difficult to mould. Also the surface finish inside a moulded tube is not smooth enough for this application, nor is the bore parallel. Drawn tubing, which has an excellent surface finish and form, is the preferred starting material, but current working methods, as described, do not provide control of both inside and outside dimensions. 
     Conventional glass hypodermic syringes are made on automatic lathes from glass by working heat-softened tube, as previously described. Low cost disposable glass syringes are generally made with the hollow needle glued into a precisely formed hole in one end of the syringe body. The manufacturing process is relatively primitive, with low production rates and high reject rates. 
     OBJECT OF THE INVENTION 
     The present invention seeks to overcome the drawbacks of current glass tube forming methods by providing a means of forming the orifice, and the inside and outside profiles of a needleless injector capsule or hypodermic syringe body, which means has excellent repeatability and is capable of high speed production. 
     SUMMARY OF THE INVENTION 
     According to the invention there is provided a method of making an article from a formable material, the article having a cavity communicating with the exterior via an orifice, wherein a blank having an open end is mounted on a first forming tool, and the open end is engaged by a second forming tool while an end region of the blank adjacent the said open end is in a condition to permit it to be formed, one of the said tools having a pin extending therefrom, and the said one tool and the other of said tools are brought together to form the said end region into a desired shape, with the pin defining the said orifice. 
     The invention further provides an apparatus for making an article from a formable material, the article having a cavity communicating with the exterior via an orifice, comprising a first forming tool for receiving an open-ended blank, and a second forming tool for engaging an end region of the blank adjacent the open end thereof to form the same, one of the said tools having a pin extending therefrom, the tools being so arranged that when they are brought together to form the said end region into a desired shape the pin defines the said orifice. 
     The pin can be on either of the forming tools, though in the embodiments described below it is preferably on the first forming tool. 
     In a preferred embodiment of the invention, a glass tube, cut to length, is placed onto a mandrel having a profile to which the glass may be formed. The mandrel has a pin at its extreme for forming the orifice. The glass is rotated and heated on the end to be formed. When it is at the optimum forming consistency, a form tool having a profile to which the outside of the tube is to be formed, is applied to the exterior of the glass tube and presses the softened glass onto the mandrel and pin. Immediately before forming, the rotation of the glass tube is stopped; alternatively the external forming tool is rotated at the same speed as the tube, so that there is no relative movement between the tube and external form tool. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     A detailed description of the invention will now follow, with reference to the accompanying drawings, in which: 
     FIG. 1 shows a centreline section through a typical glass capsule, assembled to the nose of an actuator or power source; 
     FIG. 2 shows a glass tube placed on a mandrel, with external form tool adjacent; 
     FIG. 3 depicts the form tools in position having pressed the glass into the required shape; 
     FIGS. 4 and 5 show modified forming methods that will accommodate wide tolerance glass tube; 
     FIG. 6 shows a hypodermic syringe body; 
     FIGS. 7 a  and  7   b  show a further modified method of forming a capsule; and 
     FIGS. 8 a  and  8   b  show yet another modified method of forming a capsule. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring first to FIG. 1, capsule  1  is a cylinder containing drug  2 , and a piston  3  in contact with drug  2 . The capsule  1  is retained in the nose  4  of a needleless injector actuator by retaining cap  5  bearing on shoulder  8  of the capsule  1 . Cap  5  may be retained by screw threads  10 , snap means or other suitable device. The discharge end of the interior of capsule  1  is characterised by a frusto-conical form  7  leading into the orifice  6 . When the injector is operated, a ram  9  biassed in direction Y is released so as to engage and drive the piston  3  to discharge the drug  2  through orifice  6 . 
     The ratio of the orifice length to diameter should be as small as practicable, and it is desirable that this should be no more than 2:1. This ratio has a significant effect on the flow resistance of the orifice: too high and the orifice resembles a tube with a corresponding increase in flow resistance. Typically, the orifice diameter may be within the range of 0.1 mm to 0.5 mm, with corresponding lengths within the range of 0.2 mm to 1.0 mm. 
     When performing an injection, the face  11  of the retainer  5  is pressed lightly on the patient&#39;s skin, and the area of face  11  provides sufficient support to prevent the injector capsule assembly sinking into the tissues. If the face  12  is flush or slightly behind face  11 , the orifice is in very light contact with the skin, and an intradermal injection will result; a firm contact—i.e. face  12  protrudes slightly from face  11 —will result in a subcutaneous injection; and if face  12  protrudes considerably from face  11  thereby displacing and compressing adipose tissue, then the injection may be intramuscular. This is, of course, a generalisation, since other factors such as pressure and orifice size may be adjusted to achieve the required injection characteristics. Nevertheless, the relationship of the capsule face and retainer face must be controlled to achieve repeatable high quality injections. 
     The purpose of the frusto-conical form  7  which joins the cylindrical section of capsule  1  to the orifice  6  is to reduce turbulent energy losses as the drug is forced into the orifice  6 , and also to minimise during injection the stresses within the glass walls of capsule  1  as the cylindrical bore reduces to the orifice  6 . 
     The foregoing description covers the essential design requirements of a needleless injector capsule: there may be small variations but the great majority of injectors use a capsule having a form similar to that described. 
     Referring now to FIG. 2, the material for the capsule  1  is a length of glass tube  1   a,  which is located over mandrel  20  and rests on tube support  23 . The mandrel  20  has a frusto-conical form  7   a,  terminating in a pin  21 . Located concentrically above the mandrel  20  is a form tool  22 , which has a forming surface  27 . A hole  24  in the form tool  22  is a close clearance fit relative to pin  21 . 
     The forming process commences by heating the tube  1   a  in the area of the frusto-conical section  7   a  of mandrel  20  to a temperature sufficient to soften the glass. Preferably, at least the mandrel  20  is rotated, (and more preferably the tube support  23  and mandrel  20  are rotated in unison, i.e. at the same speed and in the same direction), together with the glass tube  1   a,  during heating, so that the temperature of the glass is evenly distributed. Alternatively, the parts may remain stationary, the glass being heated by a ring burner. When the optimum temperature is reached, the form tool  22  is pressed onto the softened glass as shown in FIG. 3, and thus shapes the glass tube  1   a  to form the capsule  1 . This is done either with the support  23  and mandrel rotating together in unison, or with both stationary. The lengths of the orifice  6  and other features are controlled by the face  26  of the form tool  22  abutting face  25  of tube support  23 , but other stop means may be equally effective. 
     The process described and illustrated by FIGS. 2 and 3 is idealised and would require an exact volume of glass tubing to be presented to the form tool. In practice, the dimensional tolerances of glass tube are quite large, and even if an accurate bore tubing is specified, the variation in wall thickness results in a wide variation in the outside diameter. FIG. 4 shows a method of overcoming this problem. The form tool  22   a  has a hole  24   a  which is substantially larger in cross-section than the corresponding pin  21   a.  This pin is shorter than the pin shown in FIG.  2 . In the illustration, hole  24   a  is frusto-conical, and has a substantially larger cross-section than the pin  21   a  at least for that length of the hole over which the pin extends. In other words, there is a substantial clearance between the pin and the surface defining the hole. The glass tube is cut so that the volume is slightly greater than required for the finished capsule, and during forming, any excess material is forced along hole  24   a  to form a blob  40 , whereby the hole formed by pin  21   a  is closed. After removing the formed tube from the mandrel and tube support, the blob  40  is cut at X—X and the cut face is flame polished to remove sharp edges and to smooth out any surface roughness. If necessary, after cutting, the face may be ground before flame polishing. 
     FIG. 5 shows another method of dealing with excess material. Again, the volume of the glass tube is slightly more than the finished capsule, and during forming, the excess glass is allowed to spread into the form tool to make a rim  50 , the length Z of which may vary according to the amount of excess glass. This method has the additional advantage that the diameter of the rim  50  is controlled, regardless of the wall thickness tolerance. 
     It is important that the orifice is formed without any glass “flash”, and whilst FIGS. 3 and 5 show pin  21  entered into hole  24 , the annular clearance between pin and hole must be very small to prevent the ingress of molten glass which would form a thin skin or “flash” across the orifice  6 . As a result, the alignment of the forming tool and mandrel is critical in FIGS. 3 and 5 to ensure that the pin  21  enters hole  24  without bending or jamming. This requires accurate and costly tools. 
     FIGS. 7 a  and  7   b  show a method of preventing flash formation around the orifice without the necessity of very accurate tool alignment. Plunger  60  is a sliding fit within forming tool  22   b  and a compression spring  64  bears on plunger  60  which carries a collar  63  fixed thereto. The total sliding movement permitted is controlled by the faces of the collar  63  and abutment faces  65  and  67  within a cavity  66  in the forming tool  22   b.  The mandrel  20   b  carries a pin  21   b  which has a flat distal face  62 , and plunger  60  has a flat distal face  61 . When the glass is formed, substantially as already described, the faces  61  and  62  cooperate to form a tight “shut-off” to prevent molten glass forming a thin skin over the end of the orifice in the capsule. The force of the shut-off is determined by the spring  64 . 
     FIGS. 8 a  and  8   b  show a similar arrangement, but in this case the pin  21   c  is spring loaded by a compression spring  64   c  and slides in mandrel  20   c.  When the forming tool  22   c  and the mandrel  20   c  are brought together to form the glass, a face  70  of pin  21   c  cooperates with a face  71  of the forming tool  22   c  to form a tight shut-off. 
     The foregoing methods of forming the glass tube may be applied with equal efficacy to the production of glass syringes, as shown in FIG.  6 . In this case, the diameter of hole  100  may be required to be closely controlled to accept a hollow needle: the needle may be bonded into the glass with a minimum thickness of adhesive. Alternatively, the frusto-conical tip  200  may be dimensioned to accept a so-called Luer-fitting needle, i.e. a needle with an adaptor having a cooperating internal taper by which means the needle may be frictionally retained on the syringe tip. 
     The method of forming tubing to make needleless injector capsules and hypodermic syringes may be applied to materials other than glass where conventional forming methods are inappropriate.