RAPID MUCOSAL GEL OR FILM INSULIN COMPOSITIONS

• US 20080096800A1
• Filed: 10/24/2007
• Published: 04/24/2008
• 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:
  US11/923,591
• Publication Number:
  US 20080096800A1
• Time in Patent Office: Days
• US Class Current: 514/6.4
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

Gel, powder, suspension, emulsions or film formulations for systemic delivery of insulin with improved stability and rapid onset of action are described herein. The formulations are preferably absorbed to a mucosal surface, most preferably via buccal or sublingual administration, although rectal, vaginal, nasal or ocular administration is possible. The formulations contain insulin in combination with a chelator and dissolution agent, and optionally additional excipients. In the preferred embodiment, the formulation contains human insulin, a zinc chelator such as EDTA and a dissolution agent such as citric acid. Following administration, these formulations are rapidly absorbed into the blood stream. The formulation is preferably a polymeric gel, powder or film which adheres to the mucosal surface, thereby enhancing uptake of the incorporated drug. In the preferred embodiment, this formulation is administered sublingually, most preferably before a meal or after a meal.

Claims

1. A composition for administration of insulin to a mucosal surface comprising insulin and an effective amount of a dissolution agent and a zinc chelator to enhance uptake and transport of the insulin through epithelial cells as compared to insulin alone or insulin in combination with a zinc chelator and HCl in a solid dosage form.

2. The composition of claim 1 wherein the dosage form is selected from the group consisting of a gel, film, powder and patch.

3. The composition of claim 1, wherein the agent is selected from the group consisting of human insulin, animal insulin and insulin analogs.

4. The composition of claim 3, wherein the agent is human insulin.

5. The composition of claim 1, wherein the chelator is selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), EGTA, trisodium citrate (TSC), alginic acid, alpha lipoic acid, dimercaptosuccinic acid (DMSA), CDTA (1,2-diaminocyclohexanetetraacetic acid).

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

7. The composition of claim 1, wherein the dissolution agent is an acid selected from the group consisting of acetic acid, ascorbic acid, citric acid, glutamic, succinic, aspartic, maleic, fumaric, and adipic acid.

8. The composition of claim 7 wherein the dissolution agent is citric acid.

9. The composition of claim 1 wherein the chelator is present in a concentration range corresponding to between 2.42×

10<sup>−

4</sup> M and 9.68×

10<sup>−

2</sup>M EDTA.

10. The composition of claim 1 wherein the dissolution agent is present in a concentration range corresponding to between 9.37×

10<sup>−

4</sup> M and 9.37×

10<sup>−

2</sup>M citric acid.

11. The composition of claim 1 wherein the zinc chelator is EDTA and the dissolution agent is citric acid and the chelator is present in a concentration of between 2.42×

10<sup>−

4</sup> M and 9.68×

10<sup>−

2</sup>M EDTA and the dissolution agent is present in a concentration of between 9.37×

10<sup>−

4</sup> M and 9.37×

10<sup>−

2</sup> M citric acid.

12. The composition of claim 1 comprising two or more layers or a coating on a layer, wherein one layer or coating comprises insulin and the other comprises at least one of the dissolution agent or chelator.

13. The composition of claim 1 comprises a coating or backing on one side of the formulation to prevent diffusion of the insulin, wherein the other side is suitable for application to the mucosal surface and release of the insulin.

14. The composition of claim 1 in the form of a film.

15. A method of treating a diabetic individual comprising administering to a mucosal tissue of the individual an effective amount of an insulin composition for administration of insulin to a mucosal surface comprising insulin and an effective amount of a dissolution agent and a zinc chelator to enhance uptake and transport of the insulin through epithelial cells as compared to insulin alone or insulin in combination with a zinc chelator and HCl in the form of a gel, film, powder or patch.

16. The method of claim 15 wherein the composition is applied to the buccal or sublingual area.