Progesterone replacement therapy

• US 5,770,227 A
• Filed: 07/17/1996
• Issued: 06/23/1998
• Est. Priority Date: 08/04/1994
• Status: Expired due to Term

• Current Assignee: Encinal Pharmaceutical Investments, LLC
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Espinal, Steven, Dong, Liang C., Wong, Patrick S. L.
• Primary Examiner(s): JORDAN, KIMBERLY R
• Application Number:
  US08/682,200
• Time in Patent Office: 706 Days
• Field of Search: 424/480, 514/177
• US Class Current: 424/480
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2004 Excipients; Inactive ingredients
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084

Abstract

A hormone replacement composition, a hormone replacement dosage form, and a method of hormone replacement are disclosed and indicated for the management of hormone replacement therapy.

Claims

1. A therapeutic composition for hormone replacement therapy, comprising 10 ng to 1200 mg of a progestin, 1 mg to 30 mg of a surfactant, 5 mg to 225 mg of an alkali carboxymethylcellulose, 0.05 mg to 20 mg of a disintegrant, and 0.5 mg to 75 mg of an osmagent.

2. The therapeutic composition for hormone replacement therapy according to claim 1, wherein the progestin is selected from the group consisting of progesterone, progestogen, medroxyprogesterone, medroxy-progesterone acetate, megestrol acetate, norethindrone, norethindrone acetate, norgestrel, hydroxyprogesterone caproate, norethisterone, norethisterone acetate, levonorgestrel, norgestimate, norethynodrel, 17-hydroxyprogesterone, 17-hydroxyprogesterone esters, 17α

-ethinyl testosterone, 17α

-ethinyl-10-nortestosterone, d-17β

-acetoxy-13β

-ethyl-17α

-ethinyl-17β

-hydroxy-gon-4-en-3-one, 13β

-ethyl-17β

-hydroxygon-4-en-3-one, chlormadrone acetate, dimethistrone, 17α

-ethinyl-17β

-acetoxy-19-norandrost-4-en-3-one oxime, 3-kelodesogestrel, desogestrel, gestodene, and gestodene acetate.

3. The therapeutic composition for hormone therapy according to claim 1, wherein the surfactant is selected from the group consisting of polyoxyethylene stearate, sesquioleic acid sorbitan, trioleic acid sorbitan, monooleic acid sorbitan, monostearic acid sorbitan, monolauric acid sorbitan, monostearic acid polyethylene glycol, monooleic acid polyoxyethylene sorbitan, monolauric acid polyoxyethylene sorbitan, polyoxyethylene monylphenylether, polyoxyethylene acetyl ether, and polyoxyethylene lauryl ether.

4. The therapeutic composition for hormone therapy according to claim 1, wherein the alkali carboxymethylcellulose is replaced by a poly(alkylene) oxide possessing a 75,000 to 350,000 molecular weight.

5. The therapeutic composition for hormone therapy according to claim 1, wherein the disintegrant is selected from the group consisting of hydorxypropylalkylcellulose, polyvinylpyrrolidone, clays, gums, carrageenan, casein, and ion-exchange resins.

6. A dosage form for delivering a hormone for hormone replacement therapy, wherein the dosage form comprises:

(a) a progestin layer comprising 10 ng to 1200 mg of a progestin, 5 mg to 225 mg of an alkali carboxymethylcellulose possessing a 75,000 to 350,000 molecular weight, 0.05 mg to 20 mg of a disintegrant selected from the group consisting of hydroxypropylalkylcellulose and polyvinylpyrrolidone, 1 mg to 30 mg of a surfactant, and 0.5 mg to 75 mg of an osmagent;

(b) a push layer comprising 50 mg to 200 mg of an alkali carboxymethylcellulose of 500,000 to 1,000,000 molecular weight, 1 mg to 20 mg of a hydroxypropylmethylcellulose of 9,000 to 150,000 molecular weight, and 0.5 mg to 100 mg of an osmagent;

(c) an inner coat that surrounds the progestin layer and the push layer, the inner coat comprising a member selected from the group consisting of hydroxyalkylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and gelatin;

(d) an outer coat that surrounds the inner coat, the outer coat comprising a semipermeable composition that is permeable to the passage of fluid and impermeable to the passage of progestin; and

,

(e) a passageway through the outer coat and the inner coat for delivering the progestin from the dosage form.

7. The dosage form for delivering a hormone for replacement therapy according to claim 6, wherein a poly(alkylene oxide) of 75,000 to 350,000 molecular weight replaced the alkali carboxymethylcellulose in the progestin layer.

8. The dosage form for delivering a hormone for replacement therapy according to claim 6, wherein a poly(alkylene oxide) of 3,000 to 7,500,000 replaced the alkali carboxymethylcellulose of the push layer.