WO2019030109A1

WO2019030109A1 - Method and an apparatus for feeding a filament and use of the apparatus for production of a pharmaceutical dosage form

Info

Publication number: WO2019030109A1
Application number: PCT/EP2018/071001
Authority: WO
Inventors: Steve ROMMEL
Original assignee: Teva Pharmaceuticals Industries Ltd.
Priority date: 2017-08-07
Filing date: 2018-08-02
Publication date: 2019-02-14
Also published as: IL272462A; EP3664990A1

Abstract

The invention refers to a method and an apparatus for feeding a filament in solid form comprising meltable material towards a means of extrusion enabling for disposing at least said material in an unsolidified state for building a three dimensional object by means of a generative production process. The inventive idea is characterized by touching the solid filament by a transport mechanism for the purpose of feeding at its circumferential surface at least along one contact in form of a contact line or a contact surface.

Description

Method and an apparatus for feeding a filament and use of the apparatus for production of a pharmaceutical dosage form

Technical Field

The invention refers to a method and an apparatus for feeding a filament in solid form comprising meltable material towards a means of extrusion enabling for disposing at least said material in an unsolidified state for building a three dimensional object by means of a generative production process.

Background of the Invention

The entry of additive manufacturing technique into the manufacture of

pharmaceutical dosage forms, like tablets, pills or suppositories comprising any number of Active Pharmaceutical Ingredients (API) and any distribution of API and/or pharmaceutically acceptable excipient and/or drug product formulation has become no longer new, it opens up the possibility of creation of detailed predetermined variation of composition within a dosage form and finally to adapt an individual distribution and dosage of at least one more API within the dosage form to the need of each single human. This kind of fabrication technique leads to personalized medication by administration of person-specific "dosage form", which is a therapeutic administration unit in form of a tablet or pill for the use of oral or anal administration.

One main challenge of producing dosage forms by additive manufacturing technique is the highly accurate dosage and distribution of the at least one AIP in the dosage form, i.e. the addition of the at least one AIP must be highly accurate.

Generally, additive manufacturing is a generic term for making 3-dimensional objects by layered material construction on basis of a binary data set representing the whole shape of the object. Among several different types of manufacturing techniques, for example powder bed processing - like Selective Laser Melting (SLM), Selective Laser Sintering (SLS), Selective Heat Sintering (SHS), Electron Beam Melting (EBM) etc.-, free form processing - like Fused Deposition Modeling (FDM), Fused Filament Fabrication (FFM) etc. -, liquid material processing - like Stereolithography (SLA), Liquid Composition Moulding (LCM) etc.- the following description focuses on a 3-D printing technique using FDM or FFM.

Here, a grid of dots or lines is applied to a working plane, similar to a normal printer. The dots or lines are thereby produced by the liquefaction of a wire-shaped plastic, the so called filament, by heating. The melted plastic material is applied by extrusion by means of a nozzle and subsequent hardening by cooling at the desired position in a grid of the working plane.

The document WO 2015/077262 discloses an extruded 3D printer input, i.e. a filament to be melted before extruding through a nozzle head. The filament comprises separate layers or sections preferably made of different materials so that layering or combining different materials simultaneously through one or more nozzles during the 3D printing process can be realized. The disclosed technique facilitates smaller layer sizes, different layer configurations as well has the potential to incorporate materials that would otherwise not be usable in standard 3D printer methods.

Summary of the Invention

It is a general object of the present invention to enhance a method for feeding a filament in solid form comprising meltable material towards a means of extrusion enabling for disposing at least said material in an unsolidified state for building a three dimensional object, preferably a pharmaceutical dosage form, by means of a generative production process, such that the preciseness of feeding the filament should be optimized. The new feeding technology may ensure that the amount of filament supplied to the means of extrusion is exactly defined so that the amount of unsolidified disposed material can be controlled accurately. The new method for feeding a filament should work especially in cases in which the filament is made of an elastically compressible plastic material. Finally it is an object of the invention to provide an apparatus for feeding a filament in the before mentioned manner.

Preferably the apparatus should be suitable for manufacturing of pharmaceutical forms having.

The object is achieved by a method given in claim 1 . Subject matter of claim 6 relates to an apparatus for feeding a filament. Claim 1 1 relates to a preferred use of the apparatus according to claim 6. All features of the independent claims can be modified advantageously by the features disclosed in the corresponding subclaims as well as in the following description especially referring to preferred embodiments.

Detailed investigations made by the applicant of feeding processes in which a filament is fed to means of extrusion, led to the result that slippery feeding can't be excluded especially in cases in which the filament has elastic properties which is often the case for example when using hydrophilic materials for the filament.

Transport mechanism known per se for the purpose of feeding a filament consist of at least two roles arranged opposite to the filament, at least one of the roles is driven and contacts the circumferential surface of the filament in a point, which was recognized as the main reason for a non-exact feed of the filament.

Therefore the inventive method for feeding a filament in a solid form comprising meltable material towards a means of extrusion enabling for dispensing at least said material in an unsolidified state for building a three dimensional object by means of a generative production process is characterized by touching the solid filament by a transport mechanism for the purpose of feeding at its circumferential surface at least along one contact in form of a contact line or a contact surface.

The inventive idea is to enlarge the contact between the transport mechanism and the circumferential surface to ensure a most secure slip-free grip between the filament and the transport mechanism without damaging or deforming the filament by excessive local contact force.

Preferably the contact between the transport mechanism and the circumferential surface of the filament is based on friction and/or form fit exclusively. In a preferred embodiment the enlargement of the contact is based on the use of a filament which cross section differs from a circular cross-sectional shape known per se such that the circumferential surface of the solid filament provides at least one planar surface section along which the at least one contact between the transport mechanism and the filament takes place. Such filaments have the cross sectional shape of a square, rectangle, triangle, half-moon or half-circle or any combination thereof.

In one embodiment the transport mechanism provides a pair of roles which contact the filament at its circumferential surface on opposite sides. At least one of the sides is planar, so that the at least one role touches the planar surface section of the filament along a contact line. The contact line is oriented perpendicular to the feeding direction along which the filament is transported by the transport mechanism. The frictional force acting along the contact line between the role and the planar surface section prevents slip and ensures that the feeding velocity of the filament exactly corresponds to the circumferential velocity of the peripheral edge of the driven role touching the filament. Further the frictional force which acts along the contact line help to stabilize the feeding direction and to prevent tilting of the filament during feeding.

In a further embodiment the feeding process will be monitored by at least one sensor generating at least one sensor signal which is basis for an actively controlled contact between the transport mechanism and the filament. For example an optical sensor may record the region of the contact between the filament and the transport mechanism, so that any deformation of the filament caused by contact forces can be detected. The sensor signal can be used to adapt the contact force instantaneously to ensure a slip-free and deformation-less transport of the filament. Also other sensor types can be used, for example ultrasound based sensors, light emitting sensor systems etc..

As an alternative to or in combination with the above mentioned measures the at least one contact between the transport mechanism and the circumferential surface of the filament is in form of a contact surface which is a further improvement for a secure and accurate feeding of the filament. The larger the contact surface the lower the risk of faulty feeding of the filament. As explained thereafter the contact between the transport mechanism and the filament can be realized by using a circulating element, for example in form of a circulating belt, having sliding or rolling contact with the circumferential surface of the solid filament providing the at least one planar surface section along which the at least one contact takes place.

In case of contacting the filament by the transport mechanism in shape of a line the contact line comprising a length I with 300 μιτι < I < 10 mm, preferably. In case of contacting the filament by the transport mechanism in shape of a surface in a preferred embodiment the contact surface comprising a surface (s) between 4 mm² < s < 400 mm².

Preferably the solid filament will be touched by the transport mechanism such that a friction force (ff) acts between the solid filament and the transport mechanism in a range between 5 N < ff < y 30N.

All the above described embodiments use frictional forces on which the transport of the filament is based. Alternatively to or in combination with the above described measures the transport mechanism can be based on form fit also. For this purpose an adapted structural interlocking of the transport mechanism into the circumferential surface of the filament is necessary. In one conceivable embodiment the filament provides a roughened or structured surface section on its circumferential surface which engages an inversely contoured surface of the at least one driven rotating or circulating element of the transport mechanism.

A further conceivable embodiment in which a form fit engagement between the filament and the transport mechanism is realized provides a gear-like structured filament on the one side and a gear-like structured rotating or circulating element on the other side of the transport mechanism both engaging in each other.

Further an inventive apparatus for feeding a filament in solid form comprising meltable material towards a means of extrusion enabling for disposing at least said material in an unsolidified state for building a three dimensional object by means of a generative production process, is disclosed having a transport mechanism being arranged separately from or integrated in the means of extrusion, which may be a printing head combined with a heating unit. Said transport mechanism further provides at least one driven rotating or circulating element staying in sliding or rolling contact with a circumferential surface of the solid filament such that the at least one driven rotating or circulating element contacts the circumferential surface at least along one contact in form of a contact line or a contact surface.

In a first preferred embodiment of the apparatus the at least one driven rotating or circulating element is a role having a rigid cylindrical jacket surface which is arranged and provided such that the role contacts a planar surface section of a solid filament in form of a contact line.

Instead of using a role with a rigid cylindrical jacket surface it offers itself to use a role having an elastically deformable cylindrical jacket surface which contacts the circumferential surface of the solid filament under defined contact pressure which causes the cylindrical jacket surface to be deformed locally such that the contact is in form a contact surface. Preferably the deformable cylindrical jacket surface is made of an elastomer or of sponge-like material.

In a further preferred embodiment the at least one driven rotating or circulating element is an endless belt spanned around a pair of roles having parallel-oriented rolling axis and at least one of the roles is driven so that the endless belt circulates around the pair of roles. The endless belt is arranged relative to the solid filament to contact the circumferential surface of the solid filament at least along one contact in form of a contact surface.

In case of using a non-elastic but flexible belt a force applied contact between a section of the circumferential surface of the solid filament and a belt portion leads to locally snuggling up of the belt portion at least around a part of the circumferential surface of the filament. Therefore it is not necessary but preferable to use a filament with at least one planar surface section rather the use of the conventional filaments having a circular cross section are suitable also for providing a contact surface.

In another embodiment the circumferential surface of the solid filament provides at least one structured surface section having for example a gear-like structure, along which the at least one contact takes place. Said structured surface section of the filament is reversed contoured to a contact surface of the at least one driven rotating or circulating element so that interaction between the transport mechanism and the circumferential surface of the filament is based on form fit only.

All the above disclosed features serve the purpose of an accurate filament

conveyance towards the means of extrusion so that the amount of disposed material meets the highest accuracy requirements. Such accuracy requirements must be met especially in the field of the production of dosage forms. For this reason dosages of API in the order of magnitude of microgram or nanogram must be exactly

determined. Such precise dosage specifications however can only be implemented with the apparatus according to the invention.

Beside of the preferred use of the apparatus for the production of a pharmaceutical dosage form wherein the solid filament contains at least one API, the device according to the invention can also be applied for the production of three dimensional objects which must met a high degree of preciseness concerning material

distribution. The filament which is used for manufacturing a pharmaceutical dosage form by 3D- printing process as described above may comprise pharma suitable polymers as a matrix material into which at least one API is mixed. The at least one API may have a concentration within the polymer matrix by volume or weight between 2% and 50 %, preferably.

Brief Description of the Figures

The invention shall subsequently be explained in more detail based on exemplary embodiments in conjunction with the drawings. The drawing

Fig. 1 a Schematically view of a feeding apparatus, a filament and means of extrusion according to the state of the art,

Fig. 1 b schematically view of an inventive apparatus for feeding a filament and a means of extrusion,

Fig. 1 c-f detailed views of different kind of preferred embodiments for

apparatus for feeding a filament in solid form,

Fig. 2a-d different cross-sectional shapes of filaments.

Detailed Description of exemplary Embodiment

Figure 1 a shows an apparatus for feeding a filament 1 towards a means of extrusion 2. The filament 1 is of circular cross section and made of solid thermoplastic material. The filament 1 is supplied to a transport mechanism 3 providing a pair of roles 31 , 32 which touch the circumferential surface of the filament on both sides in a point-like manner. One of the roles 32 is driven so that the filament 1 is forced in a downward direction towards the means of extrusion 2 in which a heating unit 4 is integrated. After entering the filament into the means of extrusion the solid thermoplastic material melts and a thin strand of unsolidified plastic material emerges from the nozzle 21 of the means of extrusion 2.

Figure 1 b shows an inventive embodiment in which a filament 1 ^* having at least one planar surface section 6 facing to one role 31 which is driven preferably. Figure 1 c shows a detailed view of the contact situation between the pair the roles 31 , 32 and the filament 1 ^*. Both roles 31 , 32 are of cylindrical shape. The driven role 31 contacts the planar surface section 6 of the filament 1 ^* along a contact line 7. Not necessarily, however advantageously the second role 32 touches the filament 1 ^* along a contact line 7'. The filament 1 ^* provides a square or rectangular cross section as shown in Fig. 1 c.

Figure 1d shows an embodiment in which at least the driven role 31 has an elastically deformable cylindrical jacket surface which is subject to deformation when pressed against the planar surface section 6 of the filament 1 ^*. Due to the force contact between the role 31 and the planar surface section 6 of the filament 1 ^* the driven role 31 forms a two-dimensional contact surface 8. In the same way the second roll 32 forms a contact surface 8' as well when touching the filament 1 ^* having a square or rectangular cross section as shown in Fig. 1 d. Due to the relatively large contact surface 8 respectively 8', an internal frictional connection is formed which excludes any slip-bearing motions between the filament 1 ^* and the roles 8, 8'.

In the embodiment of Figure 1 e the transport mechanism 3 provides a pair of roles 31 , 33 having parallel oriented rolling axis A1 , A2, at least one of the two roles 31 is driven. And endless belt 9 is spanned around the pair of roles 31 , 33 and circulates around both roles in the given direction of Figure 1 e. The endless belt 9 is arranged relative to the solid filament 1 ^* to contact the circumferential surface of the solid filament 1 ^* at least along one contact in form of a contact surface 8^*. Due to the flexibility of the belt 9 it is not necessarily but advantageously that the cross section of the filament 1 ^* is of a rectangular or square form. On the opposite side of the filament 1 ^* towards the belt arrangement a role 32 is sufficient to absorb the pressing force acting from the belt onto the filament 1 ^*.

In contrast to the embodiments shown in Figures 1 b to 1 e in which feeding of the filament 1 ^* is based on frictional force only, the embodiment of Fig. 1f shows a feeding mechanism which acts on form fit between the filament 1 ^** and the transport mechanism 3. The transport mechanism 3 in Fig. 1f provides a rotating element 1 1 providing an outer contour 12 which interpose into a structured surface section 13 of the filament 1 ^**. The structured surface section 13 is reversed contoured to the outer contour of the driven rotating element 1 1 .

As in case of the embodiment shown in Fig. 1 e the role 32 arranged at the opposite side of the filament 1 ^** absorbs the contact pressure which is directed by the rotating element 1 1 onto the filament 1 ^**.

Figure 2 a-d show preferred cross sectional shapes of a filament 1 ^* which all provide at least one planar surface section facing towards a driven rotating or circulating element of the transport mechanism. Figure 2a shows a square, Figure 2b a rectangular, Figure 2c a triangle and Figure 2d a half moon cross section. The shown cross sections can also be combined with a structure surface section 13 as shown in Figure 1f at least along one planar surface section 6.

List of References Numerous

Ί _* /| _** Filament

2 Means of extrusion

21 nozzle

3 Transport mechanism

31 Driven roll

32, 33 Roll

4 Heating unit

5 Strand

6 Planar surface section

7 Contact line

8, 8', 8^* Contact surface

9 Belt

10 Contact surface

1 1 Rotating element

12 Outer contour

13 Structure surface section

Claims

1 . Method for feeding a filament in solid form comprising meltable material towards a means of extrusion enabling for disposing at least said material in an unsolidified state for building a three dimensional object by means of a generative production process,

wherein the solid filament will be touched by a transport mechanism for the purpose of feeding at its circumferential surface at least along one contact in form of a contact line or a contact surface.

2. Method according to claim 1 ,

wherein the contact between the transport mechanism and the circumferential surface of the filament is based on friction and/or form fit exclusively.

3. Method according to claim 1 or 2

wherein the contact between the transport mechanism and the circumferential surface of the filament can be adjusted depending on the physical material properties of the filament such that feeding is slip-free.

4. Method according to one of the claims 1 to 3,

wherein the contact between the transport mechanism and the circumferential surface of the filament can be monitored by at least one senor generating at least one sensor signal which is basis for an actively controlled contact.

5. Method according to one of the claims 1 to 4,

wherein the transport mechanism provides at least one driven rotating or circulating element staying in sliding or rolling contact with the circumferential surface of the solid filament providing at least one planar surface section along which the at least one contact takes place.

6. Method according to one of the claims 1 to 5,

wherein the solid filament will be touched by the transport mechanism such that the contact is in form

a) of the contact line comprising a length (I) 300 μιτι < I < 10 mm or

b) of the contact surface comprising a surface (s) 4 mm² < s < 400 mm².

7. Method according to one of the claims 2 to 6,

wherein the solid filament will be touched by the transport mechanism such that a friction force (ff) acts between the solid filament and the transport mechanism in a range between 5 N < ff < y 30N.

8. Apparatus for feeding a filament in solid form comprising meltable material towards a means of extrusion enabling for disposing at least said material in an unsolidified state for building a three dimensional object by means of a generative production process,

wherein a transport mechanism is arranged separately from or integrated in the means of extrusion, and

said transport mechanism provides at least one driven rotating or circulating element staying in sliding or rolling contact with a circumferential surface of the solid filament such that the at least one driven rotating or circulating element contacts the circumferential surface at least along one contact in form of a contact line or a contact surface.

9. Apparatus according to claim 8,

wherein the at least one driven rotating or circulating element is a role having a rigid cylindrical jacket surface,

the circumferential surface of the solid filament provides at least one planar surface section, and

the at least one role is arranged to contact the planar surface section of the solid filament in form of a contact line.

10. Apparatus according to claim 8,

wherein the at least one driven rotating or circulating element is a role having an elastically deformable cylindrical jacket surface, and

the at least one role is arranged to contact the circumferential surface of the solid filament with a contact pressures which causes the cylindrical jacket surface to be deformed locally such that the contact is in form of a contact surface.

1 1 . Apparatus according to claim 8,

wherein the at least one driven rotating or circulating element is an endless belt spanned around a pair of roles having parallel-oriented rolling axes and at least one of the roles is driven so that the endless belt circulates around the pair of roles, and the endless belt is arranged relative to the solid filament to contact the circumferential surface of the solid filament at least along one contact in form of a contact surface.

12. Apparatus according to one of the claims 8 to 1 1 ,

wherein said circumferential surface of the solid filament provides at least one structured surface section along which the at least one contact takes place, and said structured surface section is reversed contoured to a contact surface of the at least one driven rotating or circulating element so that interaction between the transport mechanism and the circumferential surface of the filament is based on form fit.

13. Use of the apparatus according to the one of the claims 8 to 12 for production of a pharmaceutical dosage form,

wherein the solid filament contains at least one active pharmaceutical ingredient (API).