Hormone replacement therapy drug formulations for topical application to the skin

• US 5,968,919 A
• Filed: 10/16/1997
• Issued: 10/19/1999
• Est. Priority Date: 10/16/1997
• Status: Expired due to Fees

• Current Assignee: MacroChem Corp. (Abeona Therapeutics Inc.)
• Original Assignee: MacroChem Corp. (Abeona Therapeutics Inc.)
• Inventors: Gyurik, Robert J., Krauser, Scott F., Samour, Carlos M.
• Primary Examiner(s): Reamer, James H.
• Application Number:
  US08/953,014
• Time in Patent Office: 733 Days
• Field of Search: 514/177, 514/467, 514/182, 424/448, 424/449
• US Class Current: 514/177
• 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 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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

Topical alcoholic or aqueous alcoholic gels containing testosterone, progesterone, estradiol or other hormones have enhanced penetration through skin by including in the formulation 2-n-nonyl-1,3-dioxolane or other hydrocarbyl derivative of 1,3-dioxolane or 1,3-dioxane or acetal, as skin penetration enhancing compound.

Claims

1. An alcoholic or aqueous alcoholic topical composition for the transdermal delivery of a hormonally active drug which comprises, on a weight basis, of the total composition:

from about 0.1 to about 10% of hormonally active drug;

from about 2 to 20% of skin penetration enhancer comprising C₇ to C₁₄ -hydrocarbyl substituted 1,3-dioxolane, 1,3-dioxane or acetal, wherein the hydrocarbyl group substituent has from about 7 to 10 carbon atoms;

0 to about 25% 1,2-propylene glycol;

from about 35 to 75% ethanol, isopropanol or mixture thereof;

0 to about 35% water; and

,

0 to about 4% of cellulosic thickener.

2. The topical composition according to claim 1 which comprises on a weight basis:

from about 1 to about 6% of hormonally active drug;

from about 2 to 15% of said enhancer;

5 to about 22% 1,2-propylene glycol;

from about 40 to 75% ethanol, isopropanol or mixture thereof;

0 to about 25% water; and

,

0 to about 3% of cellulosic thickener.

3. The topical composition according to claim 1 which comprises, on a weight basis:

from about 1.0 to about 4% of hormonally active drug;

from about 5 to 10% of said enhancer;

5 to about 20% 1,2-propylene glycol;

from about 50 to 75% ethanol, isopropanol or mixture thereof;

0 to about 25% water; and

,

0 to about 2% of cellulosic thickener.

4. The topical composition according to claim 1 wherein the hormonally active drug is an estrogen, progesterone or androgen or mixture thereof.

5. The topical composition according to claim 4 wherein the hormonally active drug comprises testosterone.

6. The topical composition according to claim 4 wherein the hormonally active drug comprises an estradiol.

7. The topical composition according to claim 4 wherein the hormonally active drug comprises progesterone.

10. The topical composition according to claim 5 comprising an ethanol/propylene glycol/water carrier system at a weight ratio of 70:

10-20;

20-10; and

about 10% by weight of 2-n-nonyl-1,3-dioxolane.

11. The topical composition according to claim 6 comprising an ethanol/propylene glycol/water carrier system at a weight ratio of 70:

10-20;

20-10; and

from about 5 to about 10% by weight of 2-n-nonyl-1,3-dioxolane.

12. The topical composition according to claim 11 comprising about 10 percent by weight of 2-n-nonyl-1,3-dioxolane.

13. The topical composition according to claim 7 comprising an ethanol/propylene glycol/water carrier system at a weight ratio of 70:

10-20;

20-10; and

from about 5 to about 10% by weight of 2-n-nonyl-1,3-dioxolane.

14. The topical composition according to claim 13 comprising about 10 percent by weight of 2-n-nonyl-1,3-dioxolane.

8. A method for the transdermal administration of hormonally active drug to a patient in need thereof which comprises

topically applying to the skin of the patient an alcoholic or aqueous alcoholic composition comprising a therapeutically effective amount of hormonally active drug in a vehicle comprising a lower alcohol selected from the group consisting of ethanol, isopropanol and mixture thereof, 1,2-alkyl diol having from 3 to 6 carbon atoms, and water in a mixing ratio of alcohol:

glycol;

water of 50-80;

5-20;

5-40, said vehicle comprising from about 70 to 90 weight percent of the composition, and from about 5 to about 20 weight percent of a skin penetration enhancing compound selected from the group consisting of 2-hydrocarbyl-1,3-dioxolane, 2-hydrocarbyl-1,3-dioxane and hydrocarbyl substituted-acetal, wherein the hydrocarbyl group has from 7 to 14 carbon atoms.

9. The method for the transdermal administration of hormonally active drug according to claim 8 wherein the drug is selected from the group consisting of testosterone, progesterone and estradiol.

15. The method according to claim 8 wherein the hormonally active drug is testosterone.

16. The method according to claim 8 wherein the hormonally active drug is estradiol.

17. The method according to claim 8 wherein the hormonally active drug is progesterone.