Stable, non-aqueous, single-phase gels and formulations thereof for delivery from an implantable device

• US 20040224903A1
• Filed: 12/19/2003
• Published: 11/11/2004
• Est. Priority Date: 12/19/2002
• Status: Abandoned Application

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Junnarkar, Gunjan, Berry, Stephen, Desjardin, Michael, Fereira, Pamela
• Application Number:
  US10/742,730
• Publication Number:
  US 20040224903A1
• Time in Patent Office: Days
• US Class Current: 514/23
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides a suspension vehicle and suspension formulations deliverable from an implantable delivery device. In particular, the suspension vehicle of the present invention allows the formulation of beneficial agent suspensions that are stable over time at ambient and physiological temperatures. In addition, the beneficial agent suspensions formed using the suspension vehicle of the present invention allow controlled delivery of beneficial agent from an implanted delivery device over sustained periods of time, even when such delivery occurs at low-flow rates, through a small-diameter delivery channel. Also included in the present invention are implantable delivery devices.

Claims

1. A pharmaceutical formulation comprising:

a single-phase vehicle, wherein the single-phase vehicle is comprised of a hydrophobic, non-polymeric material that accounts for about 75 wt % to about 100 wt % of the single-phase vehicle; and

a beneficial agent suspended within the single-phase vehicle.

2. The pharmaceutical formulation of claim 1, wherein the hydrophobic, non-polymeric material is selected from hydrophobic saccharide materials, organogels, and lipid materials.

3. The pharmaceutical formulation of claim 1, wherein the hydrophobic, nonpolymeric material is SAIB.

4. The pharmaceutical formulation of claim 1, wherein the single-phase vehicle is formulated to exhibit a viscosity ranging from about 500 to about 1,000,000 poise.

5. The pharmaceutical formulation of claim 4, wherein the single-phase viscous vehicle is formulated to exhibit a viscosity ranging from about 1,000 to about 30,0000 poise.

6. The pharmaceutical formulation of claim 1, wherein the single-phase vehicle further comprises an additional material selected from adjuvants and excipients, and the additional material included in the single-phase vehicle accounts for about 25 wt % or less of the single-phase vehicle.

7. The pharmaceutical formulation of claim 6, wherein the additional material accounts for no more than 15 wt % of the single-phase vehicle.

8. The pharmaceutical formulation of claim 6, wherein the additional material accounts for no more than 10 wt % of the sinsingle-phase vehicle.

9. The pharmaceutical formulation of claim 6, wherein the additional material accounts for no more than 5 wt % of the single-phase vehicle.

10. The pharmaceutical formulation of claim 1, wherein the hydrophobic, non-polymeric material comprises SAIB and the SAIB accounts for at least 75 wt % of the single-phase vehicle.

11. The pharmaceutical formulation of claim 1, wherein the hydrophobic, non-polymeric single-phase vehicle comprises SAIB and the SAIB accounts for at least 85 wt % of the single-phase vehicle.

12. The pharmaceutical formulation of claim 1, wherein the hydrophobic, non-polymeric single-phase vehicle comprises SAIB and the SAIB accounts for at least 90 wt % of the single sinle-phase vehicle.

13. The pharmaceutical formulation of claim 1, wherein the beneficial agent is a particulate material.

14. The pharmaceutical formulation of claim 1, wherein the beneficial agent is a particulate material and the beneficial agent accounts for 25 wt % or less of the pharmaceutical formulation.

15. The pharmaceutical formulation of claim 1, wherein the beneficial agent is a particulate material and the beneficial agent accounts for between about 0.1 wt % and 15 wt % of the pharmaceutical formulation.

16. The pharmaceutical formulation of claim 1, wherein the beneficial agent is a particulate material and the beneficial agent accounts for between about 0.4 wt % and 5 wt % of the pharmaceutical formulation.

17. The pharmaceutical formulation of claim 1, wherein the beneficial agent comprises a material selected from peptides, proteins, nucleotides, polymers of amino acids or nucleic acid residues, hormones, viruses, and antibodies that are naturally derived, synthetically produced, or recombinantly produced.

18. The pharmaceutical formulation of claim 1, wherein the beneficial agent comprises a material selected from lipoproteins, glycosylated proteins, proteins and protein substances having D-amino acids.

19. The pharmaceutical formulation of claim 1, wherein the beneficial agent comprises a material selected from baclofen, GDNF, neurotrophic factors, conatonkin G, Ziconotide, clonidine, axokine, anitsense oligonucleotides, adrenocorticotropic hormone, angiotensin I and II, atrial natriuretic peptide, bombesin, bradykinin, calcitonin, cerebellin, dynorphin N, alpha and beta endorphin, endothelin, enkephalin, epidermal growth factor, fertirelin, follicular gonadotropin releasing peptide, galanin, glucagon, gonadorelin, gonadotropin, goserelin, growth hormone-releasing peptide, histrelin, insulin, interferons, leuprolide, LHRH, motilin, nafarerlin, neurotensin, oxytocin, relaxin, somatostatin, substance P, tumor necrosis factor, triptorelin, vasopressin, growth hormone, nerve growth factor, blood clotting factors, ribozymes, and antisense oligonucleotides.

20. An implantable pump comprising a pharmaceutical formulation, the pharmaceutical formulation comprising:

a single-phase vehicle, wherein the single-phase vehicle is comprised of a hydrophobic, non-polymeric material that accounts for about 75 wt % to about 100 wt % of the single-phase vehicle; and

a beneficial agent suspended within the single-phase vehicle.

21. The implantable pump of claim 20, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of up to about 5 ml/day.

22. The implantable pump of claim 20, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of between about 0.5 and 5 μ

l/day.

23. The implantable pump of claim 20, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of between about 1.0 and 1.5 μ

l/day.

24. A pharmaceutical formulation comprising:

a single-phase vehicle formulated to exhibit a viscosity of between 500 and 1,000,000 poise comprised of a hydrophobic, non-polymeric material that accounts for about 75 wt % to about 100 wt % of the single-phase vehicle, wherein the hydrophobic non-polymeric material is selected from hydrophobic saccharide materials, organogels, and lipid materials; and

a beneficial agent suspended within the single-phase vehicle, wherein the beneficial agent is suspended as a particulate material and accounts for between about 0.1 wt % and 15 wt % of the pharmaceutical formulation.

25. The pharmaceutical formulation of claim 24, wherein the single-phase vehicle further comprises an additional material selected from adjuvants and excipients, and the additional material included in the single-phase vehicle accounts for about 25 wt % or less of the single-phase vehicle.

26. The pharmaceutical formulation of claim 25, wherein the additional material accounts for no more than 15 wt % of the single-phase vehicle.

27. The pharmaceutical formulation of claim 26, wherein the additional material accounts for no more than 10 wt % of the single-phase vehicle.

28. The pharmaceutical formulation of claim 27, wherein the additional material accounts for no more than 5 wt % of the single-phase vehicle.

29. The pharmaceutical formulation of claim 24, wherein the hydrophobic non-polymeric material comprises SAIB and the SAIB accounts for at least 75 wt % of the single-phase vehicle.

30. The pharmaceutical formulation of claim 24, wherein the hydrophobic, non-polymeric material comprises SAIB and the SAIB accounts for at least 85 wt % of the single-phase vehicle.

31. The pharmaceutical formulation of claim 24, wherein the hydrophobic, non-polymeric material comprises SAIB and the SAIB accounts for at least 90 wt % of the single-phase vehicle.

32. An implantable pump comprising a pharmaceutical formulation, the pharmaceutical formulation comprising:

a single-phase vehicle formulated to exhibit a viscosity of between 500 and 1,000,000 poise comprised of a hydrophobic non-polymeric material that accounts for about 75 wt % to about 100 wt % of the single-phase vehicle, wherein the hydrophobic non-polymeric material is selected from hydrophobic saccharide materials, organogels, and lipid materials; and

a beneficial agent suspended within the single-phase vehicle, wherein the beneficial agent is suspended as a particulate material and accounts for between about 0.1 wt % and 15 wt % of the pharmaceutical formulation.

33. The implantable pump of claim 32, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of up to about 5 ml/day.

34. The implantable pump of claim 32, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmacuetical pharmaceutical formulation at a flow rate of between about 0.5 and 5 μ

l/day.

35. The implantable pump of claim 32, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of between about 1.0 and 1.5 μ

l/day.

36. A pharmaceutical formulation comprising:

a single-phase vehicle formulated to exhibit a viscosity ranging between 1,000 and 30,000 poise, wherein the single-phase vehicle is comprised of SAIB and the SAIB accounts for 90 wt % or more of the single-phase vehicle; and

a beneficial agent suspended within the single-phase vehicle, wherein the beneficial agent is suspended as a particulate material and the beneficial agent accounts for between about 0.4 wt % and 5 wt % of the pharmaceutical formulation.

37. An implantable pump comprising a pharmaceutical formulation, the pharmaceutical formulation comprising:

a single-phase vehicle formulated to exhibit a viscosity ranging between 1,000 and 30,000 poise, wherein the single-phase vehicle is comprised of SAIB and the SAIB accounts for 90 wt % or more of the single-phase vehicle; and

a beneficial agent suspended within the single-phase vehicle, wherein the beneficial agent is suspended as a particulate material and the beneficial agent accounts for between about 0.4 wt % and 5 wt % of the pharmaceutical formulation.

38. The implantable pump of claim 37, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of up to about 5 ml/day.

39. The implantable pump of claim 37, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of between about 0.5 and 5 μ

l/day.

40. The implantable pump of claim 37, wherein the implantable pump is configured and the pharmaceutical formulation is formulated to deliver the pharmaceutical formulation at a flow rate of between about 1.0 and 1.5 μ

l/day.