Implantable device for long-term delivery of drugs

• US 9,561,352 B2
• Filed: 03/11/2010
• Issued: 02/07/2017
• Est. Priority Date: 03/12/2009
• Status: Active Grant

• Current Assignee: Delpor, Inc.
• Original Assignee: Delpor, Inc.
• Inventors: Martin, Francis J., Kang, Ling-Ling
• Primary Examiner(s): Desanto, Matthew F
• Application Number:
  US12/918,369
• Publication Number:
  US 20110106006A1
• Time in Patent Office: 2,525 Days
• Field of Search: 6048901-8921, 424/422, 424/468, 424/473, 424/423, 424/426, 424/438, 424/472
• US Class Current: 1/1
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61M 31/002 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 Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

A device for sustained delivery of a poorly water soluble drug is described. A drug reservoir within the device, when in operation, contains an aqueous suspension of the drug mixed with a suspension of an excipient that, in one embodiment, generates acidic groups for a sustained period of time to maintain a desired pH in the aqueous suspension that in turn provides a constant concentration of a soluble form of the drug.

Claims

1. A drug delivery device, comprising:

a non-erodible, non-porous housing member defining a reservoir, said housing member having a water impermeable outer surface and first and second opposing ends;

a porous partition positioned in the first end of the housing member;

contained within said reservoir, a drug formulation comprised of a sparingly water soluble drug and a solubility-modifying excipient, said sparingly water soluble drug having a soluble form and an insoluble form, wherein the insoluble form of the drug is retained in the reservoir, and wherein said solubility-modifying excipient is capable of generating acid groups to provide a concentration of the drug, in an aqueous suspension when the drug formulation is hydrated, to provide release of a therapeutic dose of the drug from the device over a period of between about 2-12 months, as the soluble form of the drug freely diffuses out of the device across said partition; and

wherein release of the therapeutic dose is dependent on pH of the drug formulation and independent of pore size of the porous partition.

2. The device according to claim 1, wherein said drug is a neuroleptic agent.

3. The device according to claim 2, wherein the drug is present in soluble and insoluble forms in a total amount of greater than 100 mg/mL.

4. The device according to claim 3, wherein the soluble fraction of drug is less than 1% of the total.

5. The device according to claim 2, wherein the neuroleptic agent is risperidone, 9-hydroxyrisperidone or a pharmaceutically acceptable salt thereof.

6. The device according to claim 2, wherein the neuroleptic agent is olanzapine, paliperidone, asenapine, haloperidol or aripiprazole or a pharmaceutically acceptable salt thereof.

7. The device according to claim 2, wherein the total amount of said neuroleptic agent loaded in said reservoir is greater than 100 mg.

8. The device according to claim 1, wherein the solubility-modifying excipient is a biocompatible, bioerodible polymer.

9. The device according to claim 8, wherein the polymer is selected from the group of polylactides, polyglycolides, and copolymers thereof.

10. The device according to claim 9, wherein the polymer is a co-polymer of polylactic acid and polyglycolic acid monomeric units, wherein the polylactic acid content is between about 50% to 100%.

11. The device of claim 1, wherein the solubility-modifying excipient is an erodible polymer or a degradable polymer.

12. The device of claim 11, wherein the polymer is polymerized from a monomer selected from the group consisting of lactic acid, glycolic acid, and lactide, glyclode.

13. The device of claim 11, wherein the polymer is a poly(lactic-co-glycolid acid) copolymer.

14. The device of claim 1, wherein the solubility-modifying excipient is water insoluble.

15. The device of claim 14, wherein the solubility-modifying excipient in its insoluble form is retained by the porous partition.

16. The device of claim 1, wherein the solubility-modifying excipient is a water insoluble polymer.

17. The device of claim 16, wherein the solubility-modifying excipient undergoes hydrolysis to form a water-soluble monomer.

18. The device according to claim 1, wherein the housing member is water impermeable.

19. The device according to claim 1, wherein the housing member is a metal.

20. The device according to claim 1, wherein the porous partition is selected from a porous polymer membrane, a sintered metallic membrane, and a ceramic membrane.

21. The device according to claim 1, wherein the drug is buprenorphine.

22. A method for treating a patient suffering from a psychotic disorder, comprising:

implanting a device according to claim 1, wherein the drug is a neuroleptic agent and is delivered at a substantially constant release rate for the period.

23. The method according to claim 22, wherein the device is implanted subcutaneously.