Transdermal delivery system, method for manufacturing the same, and transdermal delivery method using the system
Disclosed is a transdermal delivery system of multiple adhesive layers having a drug-free adhesive layer as an intermediate layer to control drug delivery rate. The transdermal delivery system enhances transdermal delivery rate in the early stage after application on skin and provides sustained control of the drug delivery rate in the intermediate and later stages. Thus, the drug delivery rate effective for treatment can be controlled in a sustained manner.
1. A transdermal delivery system comprising:
a first adhesive layer comprising a drug;
a drug-free second adhesive layer provided below the first adhesive layer so as to contact with the first adhesive layer and controlling a delivery rate of the drug; and
a third adhesive layer provided below the second adhesive layer so as to contact with the second adhesive layer and comprising the drug,
wherein the drug-free second adhesive layer is in contact with the first adhesive layer on its one surface and is in contact with the third adhesive layer on the opposite surface, and wherein the first adhesive layer and the third adhesive layer each have a solubility for the drug 1.1 to 50 times larger than the solubility of the second adhesive layer for the drug.
2. The transdermal delivery system according to claim 1 , wherein an adhesive of the first adhesive layer is the same as or different from that of the third adhesive layer.
3. The transdermal delivery system according to claim 2 , wherein the adhesive of the first adhesive layer is the same as that of the third adhesive layer.
4. The transdermal delivery system according to claim 1 , wherein an adhesive of the first adhesive layer or the third adhesive layer is one or more selected from a group consisting of an acrylate adhesive, a rubber adhesive, a silicone adhesive and an acrylate-rubber copolymer adhesive.
5. The transdermal delivery system according to claim 4 , wherein the adhesive of the first adhesive layer or the third adhesive layer is an acrylate adhesive or an acrylate-rubber copolymer adhesive.
6. The transdermal delivery system according to claim 5 , wherein the acrylate-rubber copolymer adhesive comprises an acrylate monomer and a rubber monomer at 95:5 to 10:90 based on weight.
7. The transdermal delivery system according to claim 1 , wherein an adhesive of the second adhesive layer is one or more selected from a group consisting of an acrylate adhesive, a rubber adhesive and a silicone adhesive.
8. The transdermal delivery system according to claim 7 , wherein the adhesive of the second adhesive layer is a rubber adhesive or a silicone adhesive.
9. The transdermal delivery system according to claim 1 , wherein the first adhesive layer/the second adhesive layer/the third adhesive layer are an acrylate adhesive/a rubber adhesive/an acrylate adhesive; or an acrylate adhesive, or an acrylate-rubber blend or copolymer adhesive/a silicone adhesive/an acrylate adhesive or an acrylate-rubber blend or copolymer adhesive.
10. The transdermal delivery system according to claim 1 , wherein one or more of the first adhesive layer and the third adhesive layer further comprises microporous silica including the drug.
11. The transdermal delivery system according to claim 10 , wherein the microporous silica is comprised in an amount of 0.001 to 15 wt % in one or more of the first adhesive layer and the third adhesive layer.
12. The transdermal delivery system according to claim 1 , wherein the drug is a central nervous system drug, an anti-inflammatory analgesic, an antidepressant, a circulatory system drug, a bronchial drug, a smoking cessation aid, a hair restorer, a whitening agent, an antidementia agent, an antispasmodic, an antianginal agent or a urinary system drug and is comprised in an amount of 1 to 50 wt % based on the total weight of the composition included in the transdermal delivery system.
13. The transdermal delivery system according to claim 12 wherein the drug is one or more selected from a group consisting of nicotine, nitroglycerin, tulobuterol, clenbuterol, fentanyl, buprenorphine, capsaicin, donepezil, rotigotine, selegiline, finasteride, dutasteride, methylphenidate and rivastigmine.
14. The transdermal delivery system according to claim 1 , wherein one or more of the first adhesive layer and the third adhesive layer comprises 0.01 to 20 wt % of a skin penetration enhancer.
15. The transdermal delivery system according to claim 1 , wherein the second adhesive layer accounts for 1 to 70 wt % of the transdermal delivery system.
16. A transdermal delivery system which is a multi-layer patch comprising:
a drug-impermeable backing layer ( 10 );
a first adhesive layer ( 20 ) contacting with the backing layer ( 10 ) and comprising a drug in an amount sufficient to provide a therapeutically effective amount;
a drug-free second adhesive layer ( 30 ) contacting with the first adhesive layer ( 20 ) and controlling a penetration rate of the drug;
a third adhesive layer ( 40 ) contacting with the second adhesive layer ( 30 ) and also with the skin, and comprising the drug in an amount sufficient to provide a therapeutically effective amount; and
a removable release layer ( 50 ) contacting with the third adhesive layer ( 40 ) and being removable before application,
wherein the drug-free second adhesive layer is in contact with the first adhesive layer on its one surface and is in contact with the third adhesive layer on the opposite surface, and wherein the first adhesive layer and the third adhesive layer each have a solubility for the drug 1.1 to 50 times larger than the solubility of the second adhesive layer for the drug.
17. A method for transdermal delivery comprising applying the transdermal delivery system according to claim 1 any one of claims 1 or 2 - 16 .
18. A method for manufacturing a transdermal delivery system, comprising:
forming a first adhesive layer comprising a drug on one side of a backing layer film;
forming a drug-free second adhesive layer controlling a delivery rate of the drug so as to contact with the first adhesive layer; and
forming a third adhesive layer comprising the drug so as to contact with the second adhesive layer,
wherein the drug-free second adhesive layer is in contact with the first adhesive layer on its one surface and is in contact with the third adhesive layer on the opposite surface, and wherein the first adhesive layer and the third adhesive layer each have a solubility for the drug 1.1 to 50 times larger than the solubility of the second adhesive layer for the drug.