Intravaginal drug delivery device
AssigneeEvestra, Inc.
InventorsZe'ev Shaked, Klaus Nickisch, James DiNunzio, Feng Zhang, Marcelo Omelczuk
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Abstract
Described herein is an intravaginal drug delivery system. In an embodiment the intravaginal drug delivery system includes a progestin and estrogen compound, and releases the active ingredients in a fixed physiological ratio over a prolonged period of time to produce a contraceptive state in a female.
Claims20
1-82. (canceled)
An intravaginal drug delivery device comprising:
- an intravaginal ring that comprises a thermoplastic matrix, one or more hydrophilic materials, a progestin, and an estrogen compound;
- and
- wherein the thermoplastic matrix comprises an ethylene vinyl acetate copolymer, and wherein the one or more hydrophilic materials are present in an amount sufficient to decrease the release rate of the progestin and the estrogen compound;
- and
- wherein the progestin and the estrogen compound are distributed homogenously throughout the intravaginal ring;
- wherein the intravaginal ring does not include a coating on the outer surface of the thermoplastic matrix that would alter the release rate of the progestin and the estrogen compound from the thermoplastic matrix during use;
- wherein the intravaginal ring has an average release rate of progestin of about 0.05 to about 5 mg per 24 hours for 4 days up to about 30 days after administration to a female subject, and wherein the intravaginal ring has an average release rate of the estrogen compound of about 0.01 to about 0.1 mg per 24 hours for 4 days up to about 30 days after administration to a female subject;
- and
- wherein the release rate of the progestin and the estrogen compound does not vary by an amount greater than about 30% of the amount released per 24 hours for 4 days up to about 30 days.
The device of claim 1, wherein the progestin compound is etonogestrel.
The device of claim 1, wherein the progestin compound is levonorgestrel.
The device of claim 1, wherein the estrogen compound is ethinylestradiol.
The device of claim 4, wherein the estrogen compound comprises a nitrated estrogen derivative having the structure:
- where R1 is hydrogen, C1-C8 alkyl, cycloalkyl, or C1-C8 acyl;
- R2 is hydrogen or C1-C8 alkyl;
- R3 is hydrogen, hydroxy or C1-C8 alkyl;
- R4 is hydrogen or C1-C8 alkyl;
- where each R5 and R6 is, independently, hydrogen or nitrate;
- and wherein at least one of R5 and R6 is a nitrate group.
The device of claim 1, wherein the one or more hydrophilic materials are present in an amount of about 5% to about 10% by weight of the intravaginal drug delivery device.
The device of claim 1, wherein the one or more hydrophilic materials comprise hydroxypropyl cellulose having a molecular weight between about 100,000 and about 900,000.
The device of claim 1, wherein the thermoplastic matrix further comprises a biodegradable polymer.
The device of claim 1, wherein the device delivers an effective amount of the progestin for at least 30 days.
The device of claim 1, wherein the thermoplastic matrix further comprises one or more antifungal compounds.
The device of claim 1, wherein the thermoplastic matrix further comprises one or more antibiotic compounds.
The device of claim 1, wherein the thermoplastic matrix further comprises one or more antiprogestin compounds.
An intravaginal drug delivery device made by the method comprising:
- forming a mixture of a thermoplastic polymer, a progestin, and an estrogen compound, wherein the thermoplastic matrix comprises an ethylene vinyl acetate copolymer and one or more hydrophilic matrix materials to form a thermoplastic polymer/progestin/estrogen mixture, wherein the one or more hydrophilic materials are present in an amount sufficient to decrease the release rate of the progestin and the estrogen compound in the intravaginal drug delivery device;
- heating the thermoplastic polymer/progestin/estrogen mixture such that at least a portion of the thermoplastic polymer is softened or melted to form a heated mixture of thermoplastic polymer, progestin, and the estrogen compound;
- and
- forming an intravaginal ring from the heated mixture;
- wherein the progestin and the estrogen compound are distributed homogenously throughout the intravaginal ring;
- and
- wherein the intravaginal ring does not include a coating on the outer surface of the thermoplastic matrix that would alter the release rate of the progestin and the estrogen compound from the thermoplastic matrix during use;
- wherein the intravaginal ring has an average release rate of progestin of about 0.05 to about 5 mg per 24 hours for 4 days up to about 30 days after administration to a female subject, and wherein the intravaginal ring has an average release rate of the estrogen compound of about 0.01 to about 0.1 mg per 24 hours for 4 days up to about 30 days after administration to a female subject;
- and
- wherein the release rate of the progestin and the estrogen compound does not vary by an amount greater than about 30% of the amount released per 24 hours for 4 days up to about 30 days.
A method of producing a contraceptive state in a subject comprising positioning an intravaginal drug delivery device in the vagina of a female, wherein the intravaginal drug delivery device comprises:
- an intravaginal ring that comprises a thermoplastic matrix, one or more hydrophilic materials, a progestin, and an estrogen compound;
- and
- wherein the thermoplastic matrix comprises an ethylene vinyl acetate copolymer, and wherein the one or more hydrophilic materials are present in an amount sufficient to decrease the release rate of the progestin and the estrogen compound;
- and
- wherein the progestin and the estrogen compound are distributed homogenously throughout the intravaginal ring;
- wherein the intravaginal ring does not include a coating on the outer surface of the thermoplastic matrix that would alter the release rate of the progestin and the estrogen compound from the thermoplastic matrix during use;
- wherein the intravaginal ring has an average release rate of progestin of about 0.05 to about 5 mg per 24 hours for 4 days up to about 30 days after administration to a female subject, and wherein the intravaginal ring has an average release rate of the estrogen compound of about 0.01 to about 0.1 mg per 24 hours for 4 days up to about 30 days after administration to a female subject;
- and
- wherein the release rate of the progestin and the estrogen compound does not vary by an amount greater than about 30% of the amount released per 24 hours for 4 days up to about 30 days.
An intravaginal drug delivery device comprising:
- an intravaginal ring that comprises a thermoplastic matrix, one or more hydrophilic materials, and a progestin;
- and
- wherein the thermoplastic matrix comprises an ethylene vinyl acetate copolymer;
- wherein the one or more hydrophilic materials comprises a hydroxyalkyl cellulose, and wherein the hydroxyalkyl cellulose is present in an amount sufficient to decrease the release rate of the progestin and the estrogen compound;
- wherein the progestin is distributed homogenously throughout the intravaginal ring;
- wherein the intravaginal ring does not include a coating on the outer surface of the thermoplastic matrix that would alter the release rate of the progestin from the thermoplastic matrix during use;
- wherein the intravaginal ring has an average release rate of progestin of about 0.05 to about 5 mg per 24 hours for 4 days up to about 30 days after administration to a female subject;
- and
- wherein the release rate of the progestin does not vary by an amount greater than about 30% of the amount released per 24 hours for 4 days up to about 30 days.
Dependencies are inferred from the claim text.