Rapid Acting Drug Delivery Compositions

• US 20070235365A1
• Filed: 06/25/2007
• Published: 10/11/2007
• Est. Priority Date: 03/12/2004
• Status: Abandoned Application

• Current Assignee: Biodel Inc. (Ipsen Sa)
• Original Assignee: Biodel Inc. (Ipsen Sa)
• Inventors: Pohl, Roderike, Steiner, Solomon
• Application Number:
  US11/767,698
• Publication Number:
  US 20070235365A1
• Time in Patent Office: Days
• US Class Current: 206/529
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48

Abstract

Drug formulations for systemic drug delivery with improved stability and rapid onset of action are described herein. The formulations may be administered via buccal administration, sublingual administration, pulmonary delivery, nasal administration, subcutaneous administration, rectal administration, vaginal administration, or ocular administration. In the preferred embodiments, the formulations are administered sublingually or via subcutaneous injection. The formulations contain an active agent and one or more excipients, selected to increase the rate of dissolution. In the preferred embodiment, the drug is insulin, and the excipients include a metal chelator such as EDTA and an acid such as citric acid. Following administration, these formulations are rapidly absorbed by the oral mucosa when administered sublingually and are rapidly absorbed into the blood stream when administered by subcutaneous injection. In one embodiment, the composition is in the form of a dry powder. In another embodiment, the composition is in the form of a film, wafer, lozenge, capsule, or tablet. In a third embodiment, a dry powdered insulin is mixed with a diluent containing a pharmaceutically acceptable carrier, such as water or saline, a metal chelator such as EDTA and an acid such as citric acid. Devices for storing and mixing these formulations are also described.

Claims

1. A composition comprising a biologically active agent, a solubilizing agent and a metal chelator, in a form suitable for sublingual or subcutaneous administration.

2. The composition of claim 1, wherein the agent is selected from the group consisting of insulin and derivatives thereof;

C-peptide;

glucagon-like peptide 1 (GLP

     1) and active fragments thereof;

human amylin and synthetic forms thereof;

parathyroid hormone (PTH) and active fragments thereof (e.g. PTH_1-34);

calcitonin;

human growth hormone (HGH);

erythropoietin (EPO);

macrophage-colony stimulating factor (M-CSF);

granulocyte-macrophage-colony stimulating factor (GM-CSF); and

interleukins.

3. The composition of claim 2, wherein the agent is insulin or a derivative thereof.

4. The composition of claim 1, wherein the chelator is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), penicillamine, alginic acid, Chlorella, Cilantro, Alpha Lipoic Acid, Dimercaptosuccinic Acid (DMSA), dimercaptopropane sulfonate (DMPS), and oxalic acid.

5. The composition of claim 4, wherein the chelator is ethylenediaminetetraacetic acid (EDTA).

6. The composition of claim 1, wherein the agent is a charged compound and wherein the chelator and solubilizing agent are present in effective amounts to mask charges on the agent.

7. The composition of claim 1 wherein the solubilizing agent is an acid selected from the group consisting of acetic acid, ascorbic acid, citric acid, and hydrochloric acid.

8. The composition of claim 1 in a form selected from the group consisting of dry powders, tablets, wafers, films, lozenges, and capsules.

9. The composition of claim 8, wherein the composition is in the form of a trilayer film or wafer suitable for sublingual delivery.

10. The composition of claim 1 in a form suitable for sublingual delivery.

11. A kit comprising a first storage container and a second storage container, wherein the first storage contain comprises a pharmaceutically active agent and wherein the second storage container comprises a solubilizing agent and a metal chelator.

12. The kit of claim 11 wherein the first container is a cap and the second container is a vial the cap is secured to, and wherein the two containers are separated by a barrier.

13. A method of delivering a biologically active agent to a patient comprising administering sublingually or via subcutaneous injection a composition comprising an effective amount of the agent, a solubilizing agent and a metal chelator.

14. The method of claim 13, wherein the agent is selected from the group consisting of insulin and derivatives thereof, C-peptide;

glucagon-like peptide 1 (GLP

     1) and active fragments thereof;

human amylin and synthetic forms thereof;

parathyroid hormone (PTH) and active fragments thereof (e.g. PTH_1-34);

calcitonin;

human growth hormone (HGH);

erythropoietin (EPO);

macrophage-colony stimulating factor (M-CSF);

granulocyte-macrophage-colony stimulating factor (GM-CSF); and

interleukins.

15. The method of claim 14, wherein the agent is insulin or a derivative thereof.

16. The method of claim 13, wherein the chelator is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), penicillamine, alginic acid, Chlorella, Cilantro, Alpha Lipoic Acid, Dimercaptosuccinic Acid (DMSA), dimercaptopropane sulfonate (DMPS), and oxalic acid.

17. The method of claim 16, wherein the chelator is ethylenediaminetetraacetic acid (EDTA).

18. The method of claim 13, wherein the agent is a charged compound and wherein the chelator and solubilizing agent are present in effective amounts to mask charges on the agent.

19. The method of claim 13, wherein the solubilizing agent is an acid selected from the group consisting of acetic acid, ascorbic acid, citric acid, and hydrochloric acid.

20. The method of claim 13, wherein the composition is in a form selected from the group consisting of dry powders, tablets, wafers, films, lozenges, and capsules.