Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device

Patent metadata

Field	Value
Publication number	US-9415004-B2
Application number	US-201213538912-A
Country	US
Kind code	B2
Filing date	Jun 29, 2012
Priority date	Dec 23, 2010
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

Abstract

Embodiments of the invention provide swallowable devices, preparations and methods for delivering drugs and other therapeutic agents within the GI tract. Many embodiments provide a swallowable device for delivering the agents. Particular embodiments provide a swallowable device such as a capsule for delivering drugs into the intestinal wall or other GI lumen. Embodiments also provide various drug preparations that are configured to be contained within the capsule, advanced from the capsule into the intestinal wall and degrade to release the drug into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the intestinal wall. Embodiments of the invention are particularly useful for the delivery of drugs which are poorly absorbed, tolerated and/or degraded within the GI tract.

First claim

What is claimed is:

1. A solid tissue penetrating member fabricated from a therapeutic preparation comprising adalimumab, the solid tissue penetrating member shaped and configured to be inserted into the intestinal wall after oral ingestion wherein upon insertion, the preparation releases adalimumab into the blood stream from the intestinal wall to achieve a C max in a shorter time period than a time period to achieve a C max for an extravascularly injected dose of adalimumab.

2. The tissue penetrating member of claim 1 , wherein a t max for the adalimumab released from the therapeutic preparation is 80% of a t max for the extravascularly injected dose of adalimumab.

3. The tissue penetrating member of claim 1 , wherein a t max for the adalimumab released from the therapeutic preparation is 50% of a t max for the extravascularly injected dose of adalimumab.

4. The tissue penetrating member of claim 1 , wherein a t max for the adalimumab released from the therapeutic preparation is 30% of a t max for the extravascularly injected dose of adalimumab.

5. The tissue penetrating member of claim 1 , wherein a t max for the adalimumab released from the therapeutic preparation is 10% of a t max for the extravascularly injected dose of adalimumab.

6. The tissue penetrating member of claim 1 , wherein the preparation is adapted for insertion into the wall of the small intestine.

7. The tissue penetrating member of claim 1 , wherein the extravascular injection is a subcutaneous injection or an intramuscular injection.

8. The tissue penetrating member of claim 1 , wherein the tissue penetrating member is adapted to be orally delivered in a swallowable capsule.

9. The tissue penetrating member of claim 8 , wherein the tissue penetrating member is adapted to be operably coupled to delivery means having a first configuration and a second configuration, the tissue penetrating member being contained within the capsule in the first configuration and advanced out of the capsule and into the intestinal wall in the second configuration.

10. The tissue penetrating member of claim 9 , wherein the delivery means comprises a least one expandable balloon having an expanded and a non-expanded state and the first configuration is the non-expanded state and the second configuration is the expanded state.

11. The tissue penetrating member of claim 1 , wherein the preparation comprises a biodegradable material which degrades within the intestinal wall to release adalimumab into the blood stream.

12. The tissue penetrating member of claim 1 , wherein the biodegradable material comprises PGLA, a sugar or maltose.

13. The tissue penetrating member of claim 1 , wherein the preparation comprises at least one pharmaceutical excipient.

14. The tissue penetrating member of claim 13 , wherein the at least one pharmaceutical excipient comprises at least one of a binder, a preservative or a disintegrant.

15. The tissue penetrating member of claim 14 , wherein the binder comprises PEG.

16. The tissue penetrating member of claim 1 , wherein the tissue penetrating member comprises a biodegradable material which degrades within the intestinal wall to release adalimumab into the blood stream.

17. The tissue penetrating member of claim 16 , wherein the biodegradable material comprises maltose or PGLA.

18. The tissue penetrating member of claim 1 , wherein a weight percent of adalimumab in the tissue penetrating member comprises between 8 to 12 percent.

19. The tissue penetrating member of claim 1 , wherein the tissue penetrating member includes a retaining feature for retaining the tissue penetrating member within the intestinal wall after insertion.

20. The tissue penetrating member of claim 19 , wherein the retaining feature comprises at least one of a barb or an inverse taper shape of the tissue penetrating member.

21. The tissue penetrating member of claim 1 , wherein the adalimumab is contained in the tissue penetrating member in a shaped section.

22. The tissue penetrating member of claim 21 , wherein the shaped section has a cylinder or pellet shape.

23. The tissue penetrating member of claim 1 , wherein the tissue penetrating member has a stiffness to be advanced completely into the intestinal wall by the application of a force to the tissue penetrating member.

24. The tissue penetrating member of claim 1 , wherein the C max achieved by delivering the preparation by insertion into the intestinal wall is up to ten times greater than a C max achieved when the preparation is delivered orally without insertion into the intestinal wall.

25. The tissue penetrating member of claim 1 , wherein the C max achieved by delivering the preparation by insertion into the intestinal wall is 10 to 100 times greater than the C max achieved when the preparation is delivered orally without insertion into the intestinal wall.

26. The tissue penetrating member of claim 1 , wherein the preparation is configured produce a release of adalimumab to produce a selectable t 1/2 in a range of 6 to 24 hours.

27. The tissue penetrating member of claim 1 , wherein the preparation is configured produce a release of adalimumab to produce a t 1/2 of 40 days.

28. The tissue penetrating member of claim 1 , wherein a dose of adalimumab in the preparation is in a range from 1 to 5 mg.

29. The tissue penetrating member of claim 28 , wherein a dose of adalimumab in the preparation is in a range from 2 to 4 mg.

30. A solid tissue penetrating member fabricated from a therapeutic preparation comprising adalimumab, and configured to penetrate and be inserted into an intestinal wall after oral ingestion, wherein upon insertion, the preparation releases adalimumab into the bloodstream from the intestinal wall to achieve a t 1/2 that is greater than a t 1/2 for orally ingested adalimumab that is not inserted into the intestinal wall.

31. The tissue penetrating member of claim 30 , wherein the t 1/2 of the adalimumab inserted into the intestinal wall is 10 to 100 times greater than the t 1/2 for the orally ingested adalimumab that is not inserted into the intestinal wall.

Assignees

• Imran Mir
• Rani Therapeutics Llc

Inventors

• Imran Mir

Classifications

• A61K9/0002 Primary

  Galenical forms characterised by the drug release technique; Application systems commanded by energy · CPC title

• A61M31/002

  Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time (artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50) · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61M5/00

  Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests ({vaccination appliances for veterinary use A61D1/025} ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; {combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16}) · CPC title

• A61K9/4808

  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 title