Skin permeation enhancer compositions comprising glycerol monolaurate and lauryl acetate

• US 5,843,468 A
• Filed: 05/13/1996
• Issued: 12/01/1998
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Burkoth, Terry L., Yum, Su LL, Beste, Russell D., Lee, Eun Soo, Gale, Robert M., Hamlin, Richard D., Taskovich, Lina T.
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/644,922
• Time in Patent Office: 932 Days
• Field of Search: 424/448, 424/449
• US Class Current: 424/448
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61P 25/22 Anxiolytics

Abstract

Compositions, devices, and methods for transdermal administration of an active agent are disclosed using a novel dual permeation enhancer mixture comprising lauryl acetate and a monoglyceride, preferably glycerol monolaurate. The dual permeation enhancer mixture comprising lauryl acetate is a potent permeation enhancer and provides stable systems which are more readily characterized.

Claims

1. A pressure sensitive adhesive composition for the transdermal administration of a therapeutic agent comprising, by weight:

(a) 0.1-30% of a therapeutic agent,

(b) 30-90% of a hydrophobic pressure sensitive adhesive,

(c) 1-40% of a permeation enhancer capable of plasticizing the hydrophobic pressure sensitive adhesive, said permeation enhancer comprising lauryl acetate and a monoglyceride.

2. A composition according to claim 1 wherein the composition is a hot melt pressure sensitive adhesive.

3. A composition according to claim 2 comprising a viscosity within the range of 10³ -10⁷ Poise.

4. A composition according to claim 3 comprising a viscosity within the range of 2×

10⁵ -10⁶ Poise.

5. A composition according to claim 1 wherein the composition comprises 1-30% glycerol monolaurate and 1-30% by weight lauryl acetate.

6. A composition according to claim 1 further comprising 1-30% by weight of a water absorbing polymer.

7. A composition according to claim 6 wherein the water absorbing polymer is selected from the group consisting of polyvinyl pyrrolidone, polyvinyl alcohol, and polyaminoacrvlates.

19. A composition according to claim 1 wherein the hydrophobic pressure sensitive adhesive comprises a polysiloxane adhesive.

8. A device for the transdermal administration of a therapeutic agent at a therapeutically effective rate comprising:

(a) a backing layer, and

(b) an agent reservoir matrix on the skin contacting surface of the backing layer comprising a polymeric blend comprising, by weight;

(i) 40-90% of a hydrophobic pressure sensitive adhesive,

(ii) 0.1-30% therapeutic agent, and

(iii) a permeation enhancer comprising 1-30% of a monoglyceride and 1-30% lauryl acetate.

9. A device according to claim 8, wherein the monoglyceride is glycerol monolaurate.

10. A device according to claim 8 wherein the agent reservoir further comprises 1-30% of a water absorbing polymer.

11. A device according to claim 10 wherein the water absorbing polymer is selected from the group consisting of polyvinyl pyrrolidone, polyvinyl alcohol, and polyaminoacrylates.

12. A device according to claim 11 wherein the water absorbing polymer is polyvinyl pyrrolidone.

13. A device according to claim 11 wherein the hydrophobic pressure sensitive adhesive is a polysiloxane adhesive.

14. A device according to claim 9 wherein the therapeutic agent is selected from the group consisting of testosterone, progesterone, nandrolone, and estradiol.

15. A device according to claim 14 wherein the therapeutic agent is testosterone.

16. A device according to claim 15 wherein the reservoir matrix comprises testosterone at or above saturation.

17. A device according to claim 10 comprising 60-90% polysiloxane adhesive, 5-25% polyvinyl pyrrolidone, 1-15% testosterone, 1-20% glycerol monolaurate, and 1-20% lauryl acetate.

18. A device according to claim 8 wherein the lauryl acetate is at least 97% pure.