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

• US 8,298,574 B2
• Filed: 01/18/2007
• Issued: 10/30/2012
• Est. Priority Date: 01/18/2006
• Status: Active Grant

• Current Assignee: Intec Pharma, Ltd. (Indaptus Therapeutics, Inc.)
• Original Assignee: Intec Pharma, Ltd. (Indaptus Therapeutics, Inc.)
• Inventors: Tsabari, Moshe, Yofe, Erez, Balshey, Avner
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): YOUNG, MICAH PAUL
• Application Number:
  US12/087,888
• Publication Number:
  US 20090304753A1
• Time in Patent Office: 2,112 Days
• Field of Search: 424/457, 424/451, 424/452, 424/458, 424/459, 424/409
• US Class Current: 424/451
• CPC Class Codes: A61J 3/00 Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
• CPC Class Codes: A61J 3/071 into the form of telescopically engaged two-piece capsules
• CPC Class Codes: A61J 3/074 Filling capsules; Related operations
• CPC Class Codes: A61J 3/078 into the form of wafers or cachets
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008
• CPC Class Codes: B29C 53/02 Bending or folding B29C53/22, B29C53/34, B29C53/36, B29C53/56 take precedence
• CPC Class Codes: B29C 53/04 of plates or sheets B29C63/04 takes precedence; bending or folding paper B31F1/0003; folding films B65H45/00
• CPC Class Codes: B29C 53/24 of plates or sheets
• CPC Class Codes: B29K 2105/0035 Medical or pharmaceutical agents
• CPC Class Codes: B29K 2105/256 Sheets, plates, blanks or films
• CPC Class Codes: B29K 2995/0056 Biocompatible, e.g. biopolymers or bioelastomers
• CPC Class Codes: B29K 2995/006 Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible
• CPC Class Codes: B29K 2995/0078 Shear strength
• CPC Class Codes: B32B 2037/268 Release layers
• CPC Class Codes: B32B 2307/542 Shear strength
• CPC Class Codes: B32B 2307/70 Other properties
• CPC Class Codes: B32B 2307/748 Releasability
• CPC Class Codes: B32B 27/08 : of synthetic resin
• CPC Class Codes: B32B 37/12 : characterised by using adhesives
• CPC Class Codes: B32B 37/185 : Laminating sheets, panels or inserts between two discrete plastic layers
• CPC Class Codes: B32B 37/26 : with at least one layer which influences the bonding during the lamination process, e.g. release layers or pressure equalising layers
• CPC Class Codes: B32B 39/00 : Layout of apparatus or plants, e.g. modular laminating systems
• CPC Class Codes: B32B 7/12 : using interposed adhesives or interposed materials with bonding properties
• CPC Class Codes: B65B 63/04 : for folding or winding articles, e.g. gloves or stockings
• CPC Class Codes: B65B 7/28 : by applying separate preformed closures, e.g. lids, covers
• CPC Class Codes: Y10T 156/1025 : to form undulated to corrugated sheet and securing to base with parts of shaped areas out of contact
• CPC Class Codes: Y10T 156/1051 : by folding

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.

Claims

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 agent-releasing formulation into a generally planer assembly to form an integrated device;

(ii) 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;

(iii) 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;

(iv) folding said integrated delivery device to form a folded integrated delivery device defining a first axis, such that the folded device has folds of increasingly smaller amplitudes upon extending away from the first axis in both directions so as to form a partially rounded cross section and 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; and

(v) 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, 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.

3. The method as claimed in claim 1, comprising at least one layer in the form of a strip attached to at least one of said one or more layers.

4. The method as claimed in claim 1, wherein said assembling comprises integration of said one or more layers to form a laminated device.

5. The method as claimed in claim 1, 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.

6. The method as claimed in claim 1, 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.

7. The method as claimed in claim 3, 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.

8. The method as claimed in claim 1, wherein said integrated device comprises two or more layers, and said assembling comprises one or more of a member selected from adhering, welding, curing or fusion of the two or more layers so as to allow integration between the same.

9. The method as claimed in claim 8, comprising applying an integration agent to said two or more layers so as to facilitate integration between the layers.

10. The method as claimed in claim 1, 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.

11. The method as claimed in claim 10, 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.

12. The method as claimed in claim 11, wherein at least one of said external layers is perforated or assumes perforations upon wetting.

13. The method as claimed in claim 1, 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.

14. The method as claimed in claim 1, for producing a gastro-retentive oral delivery device.

15. The method as claimed in claim 1, 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, wherein at least one 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, and controlling upwardly and downwardly movement of said central finger and at least one pair of secondary fingers towards the said other corrugated surface; and

pressing the two opposite faces one towards the other such said device is formed wherein said folds correspond to said corrugated surfaces.