Solubility enhancement of drugs in transdermal drug delivery systems and methods of use

• US 6,465,004 B1
• Filed: 06/05/2000
• Issued: 10/15/2002
• Est. Priority Date: 06/05/1999
• Status: Expired due to Term

• Current Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Original Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Inventors: Rossi-Montero, Sylvia, Houze, David, Mantelle, Juan, Kanios, David
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): GHALI, ISIS A D
• Application Number:
  US09/586,906
• Time in Patent Office: 862 Days
• Field of Search: 424/449, 424/448, 424/443
• US Class Current: 424/448
• CPC Class Codes: A61K 9/7061 Polyacrylates
• 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

Abstract

A composition and method for the continuous and controlled transdermal delivery of an active agent comprising a pharmaceutically acceptable active agent carrier and cellulose derivative which provides a solubilizing and stabilizing effect on the active agents incorporated therein.

Claims

1. A transdermal drug delivery system comprising

a pharmaceutically acceptable non-aqueous pressure-sensitive adhesive carrier composition comprising a blend of,

(i) one or more adhesives selected from the group consisting of polyacrylates, polysiloxanes, silicones, rubbers, gums, polyisobutylenes, polyvinylethers, polyurethanes, styrene block copolymers, styrene/butadiene polymers, polyether block amide copolymers;

ethylene/vinyl acetate copolymers, and vinyl acetate based adhesives,

(ii) cellulose acetate butyrafe which is insoluble in water and substantially soluble in the adhesive carrier composition, and having a butyryl content of at least 30%, as a recrystallization inhibitor, and

(iii) a therapeutically effective amount of one or more active agents.

2. The system according to claim 1, wherein the pressure-sensitive adhesive includes a hydroxy functional polyacrylate adhesive.

3. The system according to claim 1, wherein the cellulose acetate butyrate is present in an amount from about 0.5% to about 20%.

4. The system according to claim 1, wherein the pressure-sensitive adhesive carrier composition further includes one or more solvents and enhancers.

5. The system according to claim 1, wherein the one or more active agents is selected from the group consisting of steroidal hormones, analgesics, anti-inflammatory agents, central nervous system agents, cardioactive agents, anti-Parkinson'"'"'s agents and anti-Alzhiemer'"'"'s agents.

6. The system according to claim 5, wherein the steroidal hormone is selected from the group consisting of estradiol, ethinyl estradiol, progesterone, norethindrone, methyltestosterone and testosterone.

7. A method of suppressing recrystallization of active agents in an adhesive carrier composition of a transdermal drug delivery system during storage comprising:

(a) preparing a pharmaceutically acceptable non-aqueous adhesive carrier composition comprising one or more active agents, and

(b) mixing into the adhesive carrier composition a cellulose ester which is insoluble in water and substantially soluble in the adhesive carrier composition.

8. The method according to claim 7, wherein the adhesive carrier composition is a pressure-sensitive adhesive.

9. The method according to claim 8, wherein the pressure-sensitiVe adhesive includes a hydroxy functional polyacrylate adhesive.

10. The method according to claim 7, wherein the cellulose ester is selected from the group consisting of cellulose acetate butyrate, cellulose acetate propionate and cellulose acetate phthalate.

11. The method according to claim 7, wherein the cellulose ester is present in an amount from about 0.5% to about 20% by weight based on the dry weight of the total adhesive carrier composition.

12. The method according to claim 10, wherein the cellulose ester is cellulose acetate butyrate.

13. The method according to claim 7, wherein the one or more active agents is selected from the group consisting of steroidal hormones, analgesics, anti-inflammatory agents, central nervous system agents, cardioactive agents, anti-Parkinson'"'"'s agents and anti-Alzhiemer'"'"'s agents.

14. The method according to claim 13, wherein the steroidal hormone is selected from the group consisting of estradiol, ethinyl estradiol, progesterone, norethindrone, methyltestosterone and testosterone.