INTRAVAGINAL DRUG DELIVERY DEVICES FOR THE DELIVERY OF MACROMOLECULES AND WATER-SOLUBLE DRUGS

• US 20090004246A1
• Filed: 06/26/2008
• Published: 01/01/2009
• Est. Priority Date: 06/26/2007
• Status: Active Grant

• Current Assignee: Allergan Pharmaceuticals International Ltd. (Abbvie Incorporated)
• Original Assignee: Warner Chilcott Company LLC (Abbvie Incorporated)
• Inventors: Woolfson, David Aaron, Malcolm, Karl
• Granted Patent: US 8,962,010 B2
• Time in Patent Office: Days
• US Class Current: 424/430
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 16/1063 env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
• CPC Class Codes: C12N 2740/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

An intravaginal drug delivery device comprises a device body comprising a hydrophobic carrier material having at least one channel defining at least one opening to the exterior of said device body, said at least one channel being adapted to receive at least one drug-containing insert; at least one drug-containing insert positioned in said at least one channel, said drug-containing insert capable of releasing a pharmaceutically effective amount of at least one drug suitable for intravaginal administration and containing about 1% to about 70% of at least one water-soluble release enhancer, both the drug and the water-soluble release enhancer dispersed in an insert carrier material; wherein said hydrophobic carrier material and said insert carrier material may be the same or different; and wherein said at least one drug-containing insert is exposed on said exterior of said device body when said intravaginal drug delivery device is in use.

Claims

1. An intravaginal drug delivery device comprising:

(a) a device body comprising a hydrophobic carrier material having at least one channel defining at least one opening to an exterior of said device body, said at least one channel being adapted to receive at least one drug-containing insert; and

(b) at least one drug-containing insert positioned in said at least one channel, said drug-containing insert being capable of releasing a pharmaceutically effective amount of at least one drug suitable for intravaginal administration and containing at least one water-soluble release enhancer in an amount ranging from about 1% to about 70% by weight of said at least one drug-containing insert, said at least one drug and said at least one water-soluble release enhancer being dispersed in an insert carrier material;

wherein said hydrophobic carrier material and said insert carrier material may be the same or different; and

wherein said at least one drug-containing insert is exposed on said exterior of said device body when said intravaginal drug delivery device is in use.

2. The intravaginal drug delivery device of claim 1, wherein said at least one drug is a macromolecular drug and wherein said at least one drug-containing insert contains said at least one water-soluble release enhancer in an amount ranging from about 1% to about 70% by weight of said at least one drug-containing insert.

3. The intravaginal drug delivery device of claim 1, wherein said at least one drug is a water-soluble drug and wherein said at least one drug-containing insert contains said at least one water-soluble release enhancer in an amount ranging from about 15% to about 70% by weight of said at least one drug-containing insert.

4. The intravaginal drug delivery device of claim 1, wherein said at least one drug is selected from proteins, RNA- or DNA-based molecules, vaccines, and combinations thereof.

5. The intravaginal drug delivery device of claim 4, wherein said proteins are selected from antibodies, antigens, adrenocorticotropic hormone, angiotensin, beta-endorphin, blood factors, bombesin, calcitonin, calcitonin gene relating polypeptide, cholecystokinin-8, colony stimulating factors, desmopressin, endothelin, enkephalin, erythropoietins, gastrins, glucagon, human atrial natriuretic polypeptide, interferons, insulin, growth factors, growth hormones, interleukins, luteinizing hormone release hormone, monoclonal antibodies, melanocyte stimulating hormone, muramyl-dipeptide, neurotensin, oxytocin, parathyroid hormone, peptide T, secretin, somatomedins, somatostatin, thyroid stimulating hormone, thyrotropin releasing hormone, thyrotropin stimulating hormone, vasoactive intestinal polypeptide, vasopressin, and their analogues or derivatives.

6. The intravaginal drug delivery device of claim 4, wherein said RNA- or DNA-based molecules are selected from oligonucleotides, aptamers, ribozymes, DNAzymes and small interfering RNAs, for either vaccination against sexually transmitted infections or microbicidal activity against sexually transmitted microorganisms.

7. The intravaginal drug delivery device of claim 4, wherein said vaccines are selected from whole viral particles, recombinant proteins, subunit proteins, DNA vaccines, plasmids, bacterial vaccines, polysaccharides and other vaccine vectors.

8. The intravaginal drug delivery device of claim 1, wherein said at least one drug is employed in an amount ranging from about 0.001% to about 50% by weight of the insert.

9. The intravaginal drug delivery device of claim 1, comprising first and second channels and first and second drug-containing inserts positioned in said first and second channels, respectively, wherein said first and second drug-containing inserts comprise drugs that may be the same or different.

10. The intravaginal drug delivery device of claim 1, comprising first, second and third channels, and first, second and third drug-containing inserts positioned in said first, second and third channels, respectively, wherein said first, second and third drug-containing inserts comprise drugs that may be the same or different.

11. The intravaginal drug delivery device of claim 1, wherein the device body is a partial or complete toroid shape.

12. The intravaginal drug delivery device of claim 1, wherein said hydrophobic carrier material is a polymeric material selected from a polydimethylsiloxane, a copolymer of dimethylsiloxane and methylvinylsiloxane, a polyurethane, and a poly(ethylene-co-vinyl acetate).

13. The intravaginal drug delivery device of claim 1, wherein said at least one water-soluble release enhancer is selected from the group consisting of sugars or their water-soluble salts;

sugar alcohols;

salts;

glycols;

water-soluble or water-swellable polysaccharides;

organic acids;

amino acids;

proteins;

nonionic surface active agents;

bile salts;

organic solvents;

polyethylene glycols;

fatty acid esters;

hydrophilic polymers, and combinations thereof.

14. The intravaginal drug delivery device of claim 1, wherein said at least one drug-containing insert contains from about 1% to about 60% of said at least one water-soluble release enhancer by weight of said at least one drug-containing insert.

15. The intravaginal drug delivery device of claim 14, wherein said at least one drug-containing insert contains from about 1% to about 55% of said at least one water-soluble release enhancer by weight of said at least one drug-containing insert.

16. The intravaginal drug delivery device of claim 1, wherein the insert carrier material is a polymeric material selected from a polydimethylsiloxane, a copolymer of dimethylsiloxane and methylvinylsiloxane, a polyurethane, and a poly(ethylene-co-vinyl acetate).

17. The intravaginal drug delivery device of claim 1, wherein said hydrophobic carrier material, said insert carrier material, or both said hydrophobic and said insert carrier materials, comprise a silicone elastomer.

18. The intravaginal drug delivery device of claim 1, wherein said at least one drug-containing insert is a substantially cylindrical rod.

19. The intravaginal drug delivery device of claim 18, wherein said at least one drug-containing insert defines a right circular cylinder and at least one end of the at least one drug-containing insert is partly or fully exposed, in use, to the vaginal environment.

20. The intravaginal drug delivery device of claim 18, wherein said at least one drug-containing insert is substantially circular in transverse cross-section and extends substantially radially, inwardly or outwardly, through the device body.

21. The intravaginal drug delivery device of claim 1, wherein said at least one drug-containing insert has a cross-sectional diameter of from about 0.5 mm to about 8 mm.

22. The intravaginal drug delivery device of claim 1, wherein said at least one drug-containing insert has a length of from about 2 mm to about 30 mm.

23. The intravaginal drug delivery device of claim 1, wherein said at least one drug-containing insert is positioned in said device body such that the cross-sectional diameter of said at least one drug-containing insert exceeds the cross-sectional diameter of said channel by an average of about 1 mm in all directions.

24. The intravaginal drug delivery device of claim 1, wherein said at least one drug-containing insert further comprises at least one pharmaceutically acceptable non-water-soluble release enhancer in an amount ranging from about 1% to about 25% by weight of the insert.

25. The intravaginal drug delivery device of claim 1, wherein the device body further comprises at least one drug, particulate filler material, diffusion inhibitor, chemical penetration enhancer, water-soluble release enhancer or combination thereof.

26. The intravaginal drug delivery device of claim 25, wherein the at least one drug in the device body is selected from the group consisting of contraceptives, pain and migraine agents, drugs for hormone replacement therapy, anxiety and depression agents, drugs for the treatment of premenstrual syndrome, drugs for the treatment of genito-urinary disorders, drugs for cervical ripening/induction of labor, antibacterials, antifungals, antimalarial agents, antiprotozoal agents, antiviral and antiretroviral agents, drugs for the treatment of endometriosis, anti-emetic drugs and osteoporosis drugs.

27. The intravaginal drug delivery device of claim 26, wherein the at least one drug is present in the device body in an amount ranging from about 0.005% to about 65% by weight of the device body.

28. The intravaginal drug delivery device of claim 25, wherein the water-soluble release enhancer in the device body is selected from the group consisting of sugars or their water-soluble salts;

sugar alcohols;

salts;

glycols;

water-soluble or water-swellable polysaccharides;

organic acids;

amino acids;

proteins;

nonionic surface active agents;

bile salts;

organic solvents;

polyethylene glycols;

fatty acid esters; and

hydrophilic polymers, and combinations thereof.

29. The intravaginal drug delivery device of claim 25, wherein said device body contains less than about 10% of said water-soluble release enhancer by weight of said device body.

30. The intravaginal drug delivery device of claim 1, wherein the device body further comprises a sheath, provided that said at least one drug-containing insert is exposed on said exterior of said device body.

31. A method of preparing the intravaginal drug delivery device of claim 1 comprising the steps of:

(a) molding said hydrophobic carrier material in the form of said device body defining at least one channel; and

(b) inserting said at least one drug-containing insert into said at least one hollow internal channel such that said drug-containing insert is exposed on said exterior of said device body.

32. The method of claim 31 further comprising the step of curing the device body.

33. A method of intravaginally administering a drug to a female comprising the step of inserting the intravaginal drug delivery device of claim 1 into the vagina.