Composition for transdermal administration of an estrogen

• US 5,891,462 A
• Filed: 06/05/1997
• Issued: 04/06/1999
• Est. Priority Date: 06/06/1996
• Status: Expired due to Term

• Current Assignee: Antares Pharma Incorporated
• Original Assignee: Permatec N.V.
• Inventors: Carrara, Dario
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/869,982
• Time in Patent Office: 670 Days
• Field of Search: 424/449, 514/944
• US Class Current: 424/449
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• 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 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00

Abstract

Pharmaceutical formulation in the form of a gel suitable for the transdermal administration of an active agent of the class of estrogens or of progestin class or of a mixture of both, comprising:

as permeation enhancers of the above said active agents a combination consisting substantially of an aliphatic alcohol having general formula CH3(CH2)nCH20H wherein n=8-16 and of a monoalkylether of diethylene glycol;

as a vehicle or carrier, a combination of an alkanol of 2÷4 C atoms, a glycol and water;

as gelling agent a polymer or copolymer of acrylic acid;

a tertiary amine as a thickening and neutralizing agent.

Claims

1. A gel for transdermal administration consisting essentially of:

an active selected from the group consisting of an estrogen, a progestin, and mixtures thereof;

a permeation enhancing effective amount of a monoalkyl ether of diethylene glycol and an aliphatic alcohol represented by CH₃ (CH₂)_n CH₂ OH, wherein n=8-16,

a mixture of a C_2-4 alkanol, a glycol and water;

a polymer or copolymer of acrylic acid; and

a tertiary amine.

2. The gel according to claim 1 wherein the active is selected from the group consisting of 17-β

-estradiol, norethindrone and mixtures thereof.

3. The gel according to claim 1 wherein the active is selected from the group consisting of 17-β

-estradiol, norethindrone acetate and mixtures thereof.

4. The gel according to claim 1 wherein the aliphatic alcohol is lauryl alcohol, the monoalkyl ether of diethylene glycol is monomethyl- or monoethyl-ether, the C_2-4 alkanol is ethanol, the glycol is propylene glycol and the tertiary amine is triethanolamine.

5. The gel according to claim 1 containing between 0.02 and 0.09% (w/w) of 17-β

-estradiol, between 0.30 and 1.50% (w/w) of norethindrone acetate, between 0.4 and 6.0% (w/w) of lauryl alcohol, between 1 and 15% (w/w) of diethylene glycol monoethyl ether, between 20 and 65% (w/w) of ethanol, between 1 and 12% (w/w) of propylene glycol, between 20 and 65% (w/w) of water, between 0.5 and 4% (w/w) of polymer or copolymer of acrylic acid, between 0.05 and 1% (w/w) of triethanolamine.

6. The gel according to claim 1 containing:

17-β

estradiol 0.06% (w/w), norethindrone acetate 1.20% (w/w), lauryl alcohol 2.00% (w/w), diethylene glycol monoethyl ether 5.00% (w/w), ethanol 44.49% (w/w), propylene glycol 6.0% (w/w), water 39.45% (w/w), polymer or copolymer of acrylic acid 1.20% (w/w), triethanolamine 0.40% (w/w), flavouring agents 0.20% (w/w).

7. The gel according to claim 1 wherein the polymer or copolymer of acrylic acid is a carbomer.

8. The gel according to claim 1 wherein the active comprises 17-β

-estradiol and norethindrone acetate in a weight ratio of 1;

20.

9. The gel according to claim 1 wherein the aliphatic alcohol is n-decanol and is present in an amount of 1% (w/w) of the gel.

10. The gel according to claim 1 wherein the aliphatic alcohol is oleyl alcohol and is present in an amount of 1% (w/w) of the gel.

11. The gel according to claim 1 wherein the active comprises 17-β

-estradiol and norethindrone in a weight ratio of 1;

8.

12. The gel according to claim 1 wherein the active comprises 17-β

-estradiol and medroxiprogesterone acetate in a weight ratio of 1;

5.

13. The gel according to claim 1 wherein the progestin is selected from the group consisting of norethindrone acetate, norethindrone, norgestimate, medroxiprogesterone, progesterone, progesterone acetate, norgestrel, chlormadinone and gestadene.

14. The gel according to claim 1 wherein the active is a mixture of an estrogen and a progestin.