Intravaginal drug delivery devices for the administration of an antimicrobial agent
View Patent ↗An intravaginal antimicrobial drug delivery device is disclosed having an antimicrobial agent dispersed throughout a biocompatible elastomeric system. Also disclosed is a method of making the antimicrobial drug delivery device.
1. An intravaginal antimicrobial drug delivery device comprising:
a therapeutically effective amount of at least one antimicrobial agent dispersed throughout a biocompatible elastomeric system that forms said delivery device,
wherein between 5 mg and 600 mg of said at least one antimicrobial agent is released during an initial 24 hour period of use, and
wherein said delivery device consists essentially of a ring.
2. The intravaginal drug delivery device of claim 1 , wherein said biocompatible elastomeric system is hydrophobic.
3. The intravaginal drug delivery device of claim 1 , wherein said antimicrobial agent is dispersed homogeneously.
4. The intravaginal drug delivery device of claim 1 , wherein the ring has a cross-sectional diameter in a range of about 2.5 to about 15 mm.
5. The intravaginal drug delivery device of claim 4 , wherein the ring has an outer diameter in a range of about 40 to about 65 mm.
6. The intravaginal drug delivery device of claim 1 , wherein said antimicrobial agent is released at a substantially first order release rate during said initial twenty four hour period of use.
7. The intravaginal drug delivery device of claim 6 , wherein said antimicrobial agent is released at a substantially zero order release rate over at least a 3 day period of time, after said initial 24 hour period of use.
8. The intravaginal drug delivery device of claim 1 , wherein the solubility in distilled water of said antimicrobial agent is not less than 1 μg/100 ml at 20° C.
9. The intravaginal drug delivery device of claim 2 , wherein said hydrophobic elastomeric system is a silicone polymer.
10. The intravaginal drug delivery device of claim 1 , wherein between 5 mg and 250 mg of said at least one antimicrobial agent is released during said initial 24 hour period of use.
11. The intravaginal drug delivery device of claim 7 , wherein between 0.25 mg and 400 mg of said at least one antimicrobial agent is released per day, for at least said 3 days following said initial 24 hour period of use.
12. The intravaginal drug delivery device of claim 1 , wherein said antimicrobial agent is selected from the group consisting of Metronidazole, Acyclovir, Clotrimazole, Fluconazole, Terconazole, Azithromycin, Erythromycin, Doxycycline, Tetracycline, Minocycline, Clindamycin, Famcyclovir, Valacyclovir, Clarithromycin, a prodrug or salt thereof and combinations thereof.
13. The intravaginal drug delivery device of claim 1 , further comprising one or more other pharmaceutically compatible agents.
14. The intravaginal drug delivery device of claim 13 , wherein said one or more pharmaceutically compatible agents are selected from the group consisting of pharmaceutical excipients, pharmacologically active agents and combinations thereof.
15. The intravaginal drug delivery device of claim 14 , wherein said pharmaceutical excipients are selected from the group consisting of buffers, polymers, fillers and combinations thereof.
16. The intravaginal drug delivery device of claim 14 , wherein said pharmaceutical excipient is selected from the group consisting of polyvinylpyrrolidone, modified cellulose ethers, microcrystalline cellulose, polyacrylic acid, carbomer, alginic acid, carrageenan, cyclodextrins, dextrin, guar gum, gelatin and xanthan gum, monosaccharides and disaccharides.
17. The intravaginal drug delivery device of claim 14 , wherein said pharmacologically active agent is selected from the group consisting of local anaesthetics, local analgesics and combinations thereof.
18. The intravaginal drug delivery device of claim 1 , wherein a particle size distribution of the antimicrobial agent is 90% particles of less than 200 microns and 50% particles of less than 50 microns.
19. An intravaginal drug delivery device comprising:
a therapeutically effective amount of Metronidazole, a prodrug or salt thereof, dispersed throughout a biocompatible elastomeric system that forms said drug delivery device,
wherein between 5 mg and 600 mg of said Metronidazole is released during an initial 24 hour period of use, and
wherein said delivery device consists essentially of a ring.
20. The intravaginal drug delivery device of claim 19 , wherein said biocompatible elastomeric system is hydrophobic.
21. The intravaginal drug delivery device of claim 19 , wherein said antimicrobial agent is dispersed homogeneously.
22. The intravaginal drug delivery device of claim 19 , wherein said ring has a cross-sectional diameter of about 6-14 mm.
23. The intravaginal drug delivery device of claim 22 , wherein said ring has an outer diameter of about 50-60 mm.
24. The intravaginal drug delivery device of claim 19 , wherein said Metronidazole, prodrug or salt thereof, is released at a substantially first order rate of about 5 to about 250 mg during said initial 24 hours period of use.
25. The intravaginal drug delivery device of claim 24 , wherein said Metronidazole, prodrug or salt thereof is released at a substantially zero order rate of about 3 to about 175 mg per day over a period for at least 3 days, after the initial 24 hour period of use.
26. The intravaginal drug delivery device of claim 19 , wherein said Metronidazole, prodrug or salt thereof, is present in an amount in a range of about 0.5 to about 80 weight percent of said device.
27. The intravaginal drug delivery device of claim 20 , wherein said hydrophobic elastomeric system is a silicone polymer.
28. The intravaginal drug delivery device of claim 27 , wherein said silicone polymer is crosslinked.
29. The intravaginal drug delivery device of claim 19 , further comprising a release enhancing excipient.
30. The intravaginal drug delivery device of claim 29 , wherein said release enhancing excipient is selected from the group consisting of polyvinylpyrrolidone, modified cellulose ethers, microcrystalline cellulose, polyacrylic acid, carbomer, alginic acid, carrageenan, cyclodextrins, dextrin, guar gum, gelatin, xanthan gum, monosaccharides and disaccharides.
31. The intravaginal drug delivery device of claim 19 , wherein a particle size distribution of the Metronidazole, prodrug or salt thereof is 90% particles of less than 200 microns and 50% particles of less than 50 microns.
32. The method of manufacturing an intravaginal antimicrobial drug delivery device comprising the steps:
(a) mixing a biocompatible elastomer with at least one antimicrobial agent in at least a therapeutically effective amount; and
(b) curing said mixture in a shape of said intravaginal drug delivery devices,
wherein said delivery device consists essentially of a ring.
33. The method according to claim 32 , wherein the biocompatible elastomer is hydrophobic.
34. The method according to claim 33 , wherein said biocompatible hydrophobic elastomer is a silicone polymer.
35. The method according to claim 32 , wherein the mixture of biocompatible elastomer and antimicrobial agent includes a crosslinking agent.
36. The method according to claim 32 , wherein said antimicrobial agent is selected from the group consisting of Metronidazole, Acyclovir, Clotrimazole, Fluconazole, Terconazole, Azithromycin, Erythromycin, Doxycycline, Tetracycline, Minocycline, Clindamycin, Fanicyclovir, Valacyclovir, Clarithromycin, a prodrug or salt thereof and combinations thereof.
37. The method according to claim 32 , wherein said antimicrobial agent is Metronidazole, a produg or salt thereof.
38. The method according to claim 32 , wherein the mixture of biocompatible hydrophobic elastomer and antimicrobial agent includes a release enhancing excipient.
39. The method according to claim 38 , wherein said release enhancing excipient is selected from the group consisting of polyvinylpyrrolidone, modified cellulose ethers, microcrystalline cellulose, polyacrylic acid, carbomer, alginic acid, carrageenan, cyclodextrins, dextrin, guar gum, gelatin, xanthan gum, monosaccharides and disaccharides.
40. An intravaginal antimicrobial drug delivery device comprising:
a therapeutically effective amount of at least one antimicrobial agent dispersed throughout a biocompatible elastomeric system that forms said delivery device,
wherein said antimicrobial agent is released at a substantially first order release rate during an initial twenty four hour period of use.
41. An intravaginal antimicrobial drug delivery device comprising:
a therapeutically effective amount of at least one antimicrobial agent dispersed throughout a biocompatible elastomeric system that forms said delivery device,
wherein the solubility in distilled water of said antimicrobial agent is not less than 1 μg/100 ml at 20° C.
42. An intravaginal antimicrobial drug delivery device comprising:
a therapeutically effective amount of at least one antimicrobial agent dispersed throughout a biocompatible elastomeric system that forms said delivery device,
wherein a particle size distribution of the antimicrobial agent is 90% particles of less than 200 microns and 50% particles of less than 50 microns.