Method and apparatus for forming delivery devices for oral intake of an agent

Abstract

Methods, systems and apparatuses are provided for producing delivery devices, preferably for oral intake of an agent. In the broadest aspect, the method comprises assembling one or more layers comprising one or more materials with an agent or an agent-releasing formulation to form an intergraded, preferably laminated device; folding said integrated delivery device to form a folded integrated delivery device; and at least partially enclosing said folded delivery device to a form suitable for oral delivery. Preferably, the integrated device comprise a first external layer of a first material; a frame of a second material mounted on the first external layer; an agent-releasing formulation housed within the frame; and a second external layer of the first material mounted on the frame.

1 . A method for producing an agent delivery device for oral intake comprising:
 (i) assembling one or more layers comprising one or more materials with an agent or an agent-releasing formulation to form an intergraded device;   (ii) folding said integrated delivery device to form a folded integrated delivery device; and   (iii) at least partially enclosing said folded delivery device to a form suitable for oral delivery.   
     
     
         2 . The method as claimed in  claim 1 , wherein said one or more layers comprise one or more polymeric materials. 
     
     
         3 . The method as claimed in  claim 2 , wherein said one or more layers comprises a single or a combination of polymers, the polymer or polymers in each layer may be the same or different from that of another layer within the device. 
     
     
         4 . The method as claimed in any one of  claims 1  to  3 , comprising at least one layer in the form of a strip attached to at least one of said one or more layers. 
     
     
         5 . The method as claimed in any one of  claims 1  to  4 , wherein at least one of said one or more layers comprise said agent or agent releasing formulation. 
     
     
         6 . The method as claimed in  claim 5 , wherein said at least one of said one or more layers comprising the agent or agent-releasing formulation, comprises one or more compartments comprising said agent or agent-releasing formulation. 
     
     
         7 . The method as claimed in any one of  claims 1  to  6 , wherein said assembling comprises integration of said one or more layers to form a laminated device. 
     
     
         8 . The method as claimed in any one of  claims 1  to  7 , comprising assembling two external layers made of a first material and sandwiching a functional layer, the functional layer comprising at least one layer in a form of a strip or plurality of strips made of a second material and comprising the agent or agent-releasing formulation. 
     
     
         9 . The method as claimed in  claim 8 , wherein said functional layer comprises a matrix comprising the agent or agent releasing formulation of a one or more layers, each layer comprising one or more compartments comprising said agent or agent-releasing formulation. 
     
     
         10 . The method as claimed in  claim 9 , wherein said agent or agent-releasing formulation is releasable from the matrix or from the compartments. 
     
     
         11 . The method as claimed in  claim 9  or  10 , wherein said matrix comprises a polymeric composition. 
     
     
         12 . The method as claimed in any one of  claims 1  to  10 , comprising assembling at least one layer of an enforcing polymeric composition having a mechanical strength such that upon unfolding of the delivery device, the enforcing polymeric composition enables retention of the device in an essentially unfolded configuration. 
     
     
         13 . The method as claimed in  claim 12 , wherein said layer of the enforcing polymeric composition is provided in the form of one or more continuous or non-continuous polymeric strips, said continuous strip optionally comprises one or more gaps, depressions or slits. 
     
     
         14 . The method as claimed in  claim 13 , wherein said layer of the enforcing polymeric composition is in the form of a continuous frame at said device's periphery. 
     
     
         15 . The method as claimed in any one of  claims 4  to  14 , comprising assembling at least one layer in a form of one or more continuous or non-continuous strips with one or more layers comprising said agent or agent-releasing formulation. 
     
     
         16 . The method as claimed in any one of  claims 4  to  15 , wherein said strips are in the form of a frame having inner boundaries defining a void, and the method comprises assembling said frame with one or more layers comprising said agent or agent-releasing formulation, such that the one or more layers comprising the agent or agent-releasing formulation is affixed, attached or integrally formed within said void. 
     
     
         17 . The method as claimed in any one of  claims 4  to  14 , wherein said strips are in the form of a frame having inner boundaries defining a void, the method comprising assembling said frame with an agent-releasing formulation, such that the agent-releasing formulation is enclosed within said void. 
     
     
         18 . The method as claimed in any one of  claims 1  to  17 , wherein said integrated device comprises two or more layers, and said assembling comprises one or more of or a member selected from adhering, welding, curing or fusion of the two or more layers so as to allow integration between the same. 
     
     
         19 . The method as claimed in  claim 18 , comprising applying an integration agent to said two or more layers so as to facilitate integration between the layers. 
     
     
         20 . The method as claimed in  claim 19 , wherein said integration agent is an adhering agent. 
     
     
         21 . The method as claimed in  claim 19  or  20 , comprising applying said integration agent by spraying onto at least a portion of said one or more layers. 
     
     
         22 . The method as claimed in any one of  claims 1  to  21 , wherein said assembling comprises at least one of the following:
 embedding said agent or agent releasing formulation into one or more layers; 
 trapping said agent or agent releasing formulation within at least two layers; 
 enveloping said agent or agent-releasing formulation within at least one polymeric membrane segment; 
 attaching said agent or agent-releasing formulation to or in at least one of said one or more layers of the device, nano- or microparticles, powder, liquid or compressed solids or a matrix. 
 
     
     
         23 . The method as claimed in any one of  claims 1  to  22 , comprising assembling two or more layers of the same or different material. 
     
     
         24 . The method as claimed in  claim 23 , comprising assembling a laminated device comprising two external layers made of a first material and sandwiching one or more layers comprising one or more strips made of a second material and comprising the agent or agent-releasing formulation. 
     
     
         25 . The method as claimed in  claim 24 , wherein at least one of said external layers is perforated or assumes perforations upon wetting. 
     
     
         26 . The method as claimed in any one of  claims 1  to  25 , wherein said folding comprises manipulation of said integrated device into a compacted integrated device which is at least five times less in dimension than that of the integrated device prior to said folding. 
     
     
         27 . The method as claimed in  claim 1 , comprising assembling at least four layers, said at least four layers comprising:
 (i) two first, essentially planar, polymeric sheet portion having outer boundaries and comprising a first polymeric material;   (ii) a second, essentially planar, polymeric sheet portion comprising a second polymeric material; said second polymeric sheet defining frame with outer boundaries and inner boundaries, the outer boundaries being of essentially the same shape as the outer boundaries of the first polymeric sheet portion and the inner boundaries defining a void area;   (iii) a third, essentially planar, polymeric sheet portion comprising said agent or agent-releasing formulation releasable from said sheet when wetted, said sheet having outer boundaries to fit within the void area;   wherein the four sheet portions are assembled such that the third sheet portion is within the void area formed from the second sheet portion and the said second sheet portion and third sheet portion being jointly sandwiched between the two first polymeric sheet portions, with all outer boundaries essentially overlapping one another.   
     
     
         28 . The method as claimed in  claim 28 , wherein said assembly provides a laminated device. 
     
     
         29 . The method as claimed in any one of  claims 1  to  28 , wherein said folding comprises:
 placing said integrated device in between two opposite faces of a press, each face having a corrugated surface with ridges of one corrugated surface being essentially opposite to troughs of the other corrugated surface and essentially fitting one into the other; and 
 pressing the two opposite faces one versus the other such that an undulated, three dimensional device is formed with undulations that correspond in shape to that of said corrugated surfaces. 
 
     
     
         30 . The method as claimed in  claim 29 , wherein said folding comprises applying a press so as to push sides of the undulated device in a direction perpendicular to said undulation, into a folded device having folds formed along ridges and troughs of the undulation. 
     
     
         31 . The method as claimed in any one of  claims 1  to  30 , wherein said at least partially enclosing comprises at least one of a member selected from wrapping, dipping, spraying, encapsulating, binding, tying, molding, enveloping and sealing. 
     
     
         32 . The method as claimed in  claim 31 , wherein said encapsulating comprises placing the folded device into a capsule base and fitting a cap of said capsule onto the capsule base so as to form an encapsulated folded delivery device. 
     
     
         33 . The method as claimed in any one of  claims 1  to  32  for producing a gastro-retentive oral delivery device. 
     
     
         34 . The method as claimed in any one of  claims 1  to  33 , for producing a delivery device with controlled release of the agent. 
     
     
         35 . A system for producing an agent delivery device for oral intake comprising:
 (i) an assembly apparatus adapted to assemble one or more layers comprising one or more materials and an agent or an agent-releasing formulation to form an intergraded device;   (ii) a folding apparatus adapted to fold the integrated device into a folded integrated device;   (iii) an enclosing apparatus adapted to at least partially enclose the folded integrated device within an enclosure to form a device in a form suitable for oral delivery.   
     
     
         36 . The system as claimed in  claim 35 , wherein said assembling apparatus is adapted to assemble an integrated device, the integrated device comprising:
 (i) a first external layer comprising a first material;   (ii) one or more functional layers mounted on said first external layer and comprising a second material and said agent or agent releasing formulation;   (iii) a second external layer comprising said first material and mounted on said functional layer.   
     
     
         37 . The system as claimed in  claim 36 , wherein said assembling apparatus is adapted to assemble an integrated device, the integrated device comprising:
 (i) a first external layer comprising a first material;   (ii) a frame mounted on said first external layer and comprising a second material, said frame having inner boundaries defining a void area;   (iii) an agent or agent releasing formulation enclosed within said void area;   (iv) a second external layer comprising said first material and mounted on said frame.   
     
     
         38 . The system as claimed in  claim 36  or  37 , wherein said assembly apparatus is adapted to assemble said agent or agent releasing formulation when said agent or agent releasing formulation is
 embedded into one or more layers; 
 trapped within at least two layers; 
 enveloped within at least one polymeric membrane segment; 
 attached to or in any one of at least one layer of the device, nano- or microparticles, powder, liquid or compressed solids or to or in a matrix. 
 
     
     
         39 . The system as claimed in any one of  claims 36  to  38 , wherein said assembling apparatus comprises a dicing apparatus adapted to cut at least one shaped piece from a sheet from a first material and at least one shaped piece from a sheet of a second material. 
     
     
         40 . The system as claimed in any one of  claims 36  to  39 , comprising an application apparatus adapted to apply an integration agent onto at least one of the devices layers prior to the assembly. 
     
     
         41 . The system as claimed in  claim 40 , wherein said application apparatus comprises a sprayer for spraying said integration agent onto at least one of the devices layers. 
     
     
         42 . The system as claimed in any one of  claims 36  to  41 , wherein said assembly apparatus is adapted to provide a laminated device by adhering, welding, curing, or fusing of the device's layers. 
     
     
         43 . The system as claimed in any one of  claims 36  to  44 , comprising a perforation apparatus adapted to provide at least one of said external layers with a plurality of perforations. 
     
     
         44 . The system as claimed in any one of  claims 36  to  43 , comprising a coating apparatus adapted to provide a coat onto at least one side of the integrated device. 
     
     
         45 . The system as claimed in  claim 44 , wherein said coating apparatus is adapted to provide powder coating following folding of the integrated device. 
     
     
         46 . The system as claimed in any one of  claims 36  to  45 , wherein said folding apparatus comprises a press with two opposite faces, each face having a corrugated surface with ridges of one corrugated surface being essentially opposite to troughs of the other corrugated surface and essentially fitting one into the other; whereby upon placing the integrated device in the press and pressing the two opposite faces one versus the other an undulated, three dimensional device is formed with undulations that correspond in shape to that of said corrugated surfaces. 
     
     
         47 . The system as claimed in  claim 46 , wherein said folding apparatus is adapted to press the undulated device in a direction perpendicular to the undulations so as to form a folded device having folds formed along ridges and troughs of the undulation. 
     
     
         48 . The system as claimed in any one of  claims 36  to  47 , wherein said enclosing apparatus comprises a capsule jig for holding a capsule base and the same or different capsule jig for holding a capsule cap, whereby upon insertion of the folded integrated device into said capsule base, said capsule cap is fitted onto said capsule base comprising the folded integrated device. 
     
     
         49 . An agent delivery device for oral intake comprising a folded single or multi-layered integrated device comprising an agent or agent releasing formulation, the folded integrated device being at least partially enclosed within or by an enclosure, said agent delivery device being prepared by the method as claimed in any one of  claims 1  to  35 . 
     
     
         50 . The oral agent delivery device as claimed in  claim 49 , wherein said integrated device comprises a folded multi-layered laminated device enclosed within a capsule. 
     
     
         51 . The oral agent delivery device as claimed in  claim 49  or  50  for controlled, gastroretentive delivery of said agent. 
     
     
         52 . A folding apparatus for folding a single or multi-layered sheet comprising a primary press with two opposite faces, each face having a corrugated surface with ridges of one corrugated surface being essentially opposite to troughs of the other corrugated surface and essentially fitting one into the other; whereby upon placing at least a portion of the single or multi-layered sheet in the primary press and pressing the two opposite faces one versus the other a three dimensional device is formed with undulations that correspond in shape to that of said corrugated surfaces. 
     
     
         53 . The folding apparatus as claimed in  claim 52 , wherein said corrugated surface is formed by a series of fingers comprising a movable central finger having a first length, and at least one pair of secondary movable fingers siding said central finger and having a second length being shorter than the first length, the folding apparatus further comprising a control utility for controlling upwardly and downwardly movement of said central finger and at least one pair of secondary fingers towards the said other corrugated surface. 
     
     
         54 . The folding apparatus of  claim 53 , comprising a movable central finger having a first length, at least one pair of secondary movable fingers siding said central finger and having a second length being shorter than the first length, and a pair or outer movable fingers having a third length being shorter than the second length, each outer finger siding one of the secondary fingers. 
     
     
         55 . The folding apparatus as claimed in  claim 53  or  54 , wherein said control utility if for controlling sequential upwardly and downwardly movement of said fingers. 
     
     
         56 . The folding apparatus as claimed in any one of  claims 52  to  55 , comprising a secondary press having opposite faces perpendicular to the undulations formed in the device following operation of the primary press, such that activation of said secondary press provides a folded device having a dimension which is at least five times smaller than that of the sheet prior to pressing. 
     
     
         57 . A method for folding a single or multi-layered sheet comprising:
 (i) placing said sheet in a folding apparatus as claimed in any one of claims  52  to  55 ;   (ii) pressing the two opposite faces of the first press one versus the other to form an undulated, three dimensional device with undulations that correspond in shape to that of said corrugated surfaces.   
     
     
         58 . The method as claimed in  claim 56 , comprising activating a secondary press so as to press the undulated device in a direction perpendicular to the direction of pressing by said first press so as to obtain a folded device having a dimension which is at least five times smaller than that of the sheet prior to pressing.