Menthol enhancement of transdermal drug delivery

• US 4,933,184 A
• Filed: 04/03/1987
• Issued: 06/12/1990
• Est. Priority Date: 12/22/1983
• Status: Expired due to Term

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: American Home Products Corporation (Pfizer Inc.)
• Inventors: Tsuk, Andrew G.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US07/034,803
• Time in Patent Office: 1,166 Days
• Field of Search: 424/449, 514/946, 514/947
• US Class Current: 424/449
• 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 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 9/7084 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

Abstract

Disclosed herein are compositions and methods for enhancing the transdermal delivery of physiologically active agents across mammalian skin or membranes and which comprise a percutaneous transfer enhancing amount of menthol and a drug.

Claims

1. In a method for use in enhancing the transfer of physiologically active agents through mammalian skin and membranes to obtain sustained delivery of said agents by topical administration the improvement which consist essentially of topically applying to the same section of mammalian skin or membrane one or more compositions together consisting essentially of an effective amount of a systemically active, water soluble or solubilizable drug, a percutaneous transfer enhancing amount of method in an amount of about 4% to about 16% by weight of said composition(s), and a pharmaceutically acceptable vehicle.

2. The improved method of claim 1 wherein each of the drug and the menthol are administered sequentially.

3. The improved method of claim 1 wherein the drug and the menthol are administered to said mammal simultaneously.

4. The improved method of claim 1 which provides at least two fold enhancement of the delivery of water solubilizable drugs and five fold enhancement of the delivery of water soluble drugs when measured in in vitro models.

5. The improved method of claim 1 which provides at least three fold enhancement of the delivery of water solubilizable drugs and ten fold enhancement of the delivery of water soluble drugs when measured in in vitro models.

6. The improved of claim 1 wherein the menthol is soluble in said vehicle.

7. The improved method of claim 1 wherein the drug is selected from the group consisting of etodolac, chlorpheniramine, propranolol, estrogens, progestogens, and their pharmaceutically acceptable salts.

8. The improved method of claim 1 wherein the drug is selected from the group consisting of cetamolol, acifran, phenylpropanolamine, ibuprofen, nicotine, diazepam, digoxin, insulin, somatostatin, isosorbide dinitrate, vinpocetine, pelrinone, hydrocortisone, and their pharmaceutically acceptable salts.

9. In a topical composition for use the transdermal and sustained delivery of physiologically active agents to mammals the improvement comprising providing at least two fold enhancement of the delivery water solubilizable drugs and five fold enhancement of the delivery of water soluble drugs contained in the composition said composition consisting essentially of an effective amount of a systemically active, water soluble or solubilizable drug;

a percutaneous transfer enhancing amount of menthol in an amount of about 4% to about 16% by weight of said composition; and

a pharmaceutically acceptable vehicle comprising at least one pharmaceutically acceptable solvent or solubilizer for the menthol.

10. The improved composition of claim 9 in which the pharmaceutically acceptable vehicle further comprises at least one pharmaceutically acceptable solvent for the drug.

11. The improved composition of claim 10 in which the solvents for each of the drug and the menthol are, in the amounts employed, at least partially miscible with each other.

12. The improved composition of claim 10 in which each of the drug and the menthol are at least partially soluble in each solvent.

13. The improved composition of claim 9 comprising a water soluble drug which provides at least ten fold enhancement of the delivery of said drug.

14. The improved composition of claim 9 comprising a water solubilizable drug which provides at least five fold enhancement of the delivery of said drug.

15. The improved composition of claim 9 wherein the drug is selected from the group consisting of etodolac, chlorpheniramine, propranolol, estrogens, progestogens, and their pharmaceutically acceptable salts.

16. The improved composition of claim 9 wherein the drug is selected from the group consisting of cetamolol, acifran, phenylpropanolamine, ibuprofen, nicotine, diazepam, digoxin, insulin, somatostatin, isosorbide dinitrate, vinpocetine, pelrinone, hydrocortisone, and their pharmaceutically acceptable sales.