Compositions and methods to effect the release profile in the transdermal administration of active agents

• US 6,638,528 B1
• Filed: 03/01/2002
• Issued: 10/28/2003
• Est. Priority Date: 01/20/2000
• Status: Active Grant

• Current Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Original Assignee: Noven Pharmaceuticals (Hisamitsu Pharmaceutical Company Incorporated)
• Inventors: Kanios, David
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Joynes, Robert M.
• Application Number:
  US10/086,457
• Time in Patent Office: 606 Days
• Field of Search: 424/448, 424/449, 424/484, 424/487, 424/488, 424/443
• US Class Current: 424/449
• 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

Compositions and methods for the transdermal delivery of active agents up to a period of seven days or more at substantially a zero-order release rate comprising a pharmaceutically acceptable adhesive matrix and a polymeric plastic material that provides a release rate regulating effect on the active agents.

Claims

1. A transdermal delivery system for providing drug delivery across skin in a mammal comprising:

(a) a pharmaceutically acceptable pressure-sensitive adhesive matrix consisting essentially of a blend of;

(i) one or more adhesives selected from the group consisting of polyacrylates, polysiloxanes, polyisobutylene, polyisoprene, styrenes, styrene block copolymers and block amide copolymers in an amount from 20% to 75% by weight based on the dry weight of the total adhesive matrix composition,

(ii) an insoluble, non-adhesive ethyl cellulose polymer having a solution viscosity in the range of 3 cps to 40 cps, alone or in combination with an insoluble, non-adhesive cellulose ester in a total amount from 2.5% to 20% by weight based on the dry weight of the total adhesive matrix composition,

(iii) at least one hydrophobic active agent,

(iv) a hydrophilic crystallization inhibitor selected from the group consisting of soluble polyvinylpyrrolidone, soluble cellulose and cellulose derivatives, and polyethylene oxide in an amount from 5% to 15% by weight based on the dry weight of the total adhesive matrix composition,

(v) a drug permeation enhancer in an amount up to 15% by weight based on the dry weight of the total adhesive matrix composition, and

(vi) a polyhydric alcohol solvent in an amount up to 20% by weight based on the dry weight of the total adhesive matrix composition;

wherein the adhesive matrix is capable of delivering the active agent at a substantially zero-order kinetic rate for period of time in excess of 72 hours.

2. The transdermal system according to claim 1, wherein the ethyl cellulose polymer has a solution viscosity in the range of 3 cps to 22 cps.

3. The transdermal system according to claim 1, wherein the ethyl. cellulose polymer is combined with an insoluble, non-adhesive cellulose ester selected from the group consisting of cellulose acetate butyrate and cellulose acetate propionate.

4. The transdermal system according to claim 1, wherein the hydrophilic crystallization inhibitor is soluble polyvinylpyrrolidone.

5. The transdermal system according to claim 1, wherein the one or more active agents are selected from the group consisting of steroidal and hormonal agents.

6. The transdermal system according to claim 5, wherein tie adhesives consist of 5%-40% by dry weight polyacrylate adhesive and 30%-90% by dry weight polysiloxane adhesive, the polydric alcohol solvent is dipropylene glycol in an amount of 5%-10% by dry weight, the permeation enhancer is oleyl alcohol in an amount of 1%-10% by dry weight, the hydrophilic crystallization inhibitor is soluble polyvinylpyrrolidone in an amount of 5%-15% by dry weight, and the hormonal agent consists of 17 β

-estradiol in an amount of 0.1%-5% by dry weight alone or in combination with norethindrone acetate in an amount of 1%-7% by dry weight, said weights based on the dry weight of the total composition.