Device for controlled release drug delivery

• US 4,764,382 A
• Filed: 04/09/1986
• Issued: 08/16/1988
• Est. Priority Date: 11/15/1984
• Status: Expired due to Fees

• Current Assignee: Hercon Laboratories Corporation
• Original Assignee: Hercon Laboratories Corporation
• Inventors: Berner, Bret, Kydonieus, Agis F.
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US06/849,670
• Time in Patent Office: 860 Days
• Field of Search: 424/19, 424/28, 424/444, 424/443, 424/434, 424/449, 424/497, 424/78, 424/80, 604/896, 604/897, 523/122, 524/569, 514/874, 514/944, 514/947, 514/509
• US Class Current: 424/449
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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

A device for the controlled release and delivery of a pharmacologically active agent, comprising a vinyl gel layer and a pharmacologically active agent uniformly dispersed in the layer in a pharmacologically effective amount, the vinyl layer comprising an emulsion polymerized polyvinyl chloride resin, a primary plasticizer for the polyvinyl chloride resin, and an organic, nonvolatile gel forming additive in an amount sufficient to form a gel.

Claims

1. A device for the controlled release and delivery of a pharmacologically active agent, comprising a gelled vinyl plastisol layer and a pharmacologically active agent uniformly dispersed in the layer in a pharmacologically effective amount,

said vinyl layer comprising an emulsion polymerized polyvinyl chloride resin, a primary plasticizer for the polyvinyl chloride resin, and an organic, nonvolatile gel forming additive in an amount sufficient to form a gel.

2. The device according to claim 1, wherein the resin is present in an amount of 10 to 75 weight percent and the primary plasticizer is present in an amount of 20 to 85 weight percent, based on the total weight of the vinyl gel layer.

3. A device as in claim 2, wherein the gel forming additive is present in an amount of from 5 to 30% by weight, based on the total weight of the vinyl gel layer.

4. A device as claimed in claim 3, wherein the pharmacologically active agent is present in an amount of 0.1% to 50% by weight, based on the total weight of the vinyl gel layer.

5. A device as in claim 1, wherein the polyvinyl chloride resin is present in an amount of from 20 to 65%, the primary plasticizer is present in an amount of from 20 to 60% by weight, the gel forming additive is present in an amount of from about 8 to 25%, and the pharmacologically active agent is present in an amount of from 0.1% to 50% by weight, based on the total weight of the vinyl gel layer.

6. A device as claimed in claim 1, wherein the gel forming additive is at least one ingredient selected from isopropylpalmitate, isopropyl myristate, mineral oil, silicone oil, unepoxidized soybean oil, castor oil, linseed oil, olive oil, or petrolatum.

7. A device as claimed in claim 1, wherein the gel forming additive is a non-ionic surfactant kor a triglyceride.

8. A device as in claim 1, wherein said primary plasticizer is dioctyl phthalate, a polymeric adipate plasticizer, epoxidized soybean oil or dioctyl adipate.

9. A device as in claim 1, wherein the pharmacologically active agent is nitroglycerin, timolol, albuterol, isosorbide dinitrate, clonidine, guanfacine, nadolol or prostaglandin.

10. A device as claimed in claim 1, wherein the pharmacologically active agent is nitroglycerin.

11. A device as claimed in claim 10, wherein the gel forming additive is isopropyl palmitate.

12. A device as claimed in claim 11, wherein the primary plasticizer is dioctyl phthalate.

13. The device according to claim 1, wherein the gel layer is opaque, has a tensile strength below 50 psi, a break elongation below 10% and a tear strength below 20 lbs/inch.

14. The device according to claim 1, including a backing layer on one side of the gel layer.

15. A device as claimed in claim 1, wherein the drug is in solid form and the gel forming additive is isopropyl palmitate or isopropyl myristate present in an amount of 15 to 25 weight percent based on the weight of the vinyl gel layer.

16. A device as claimed in claim 1, wherein the drug is in liquid form and the gel forming additive is isopropyl palmitate or isopropyl myristate present in an amount of 5 to 15 weight percent based on the weight of the vinyl gel layer.

17. A device as claimed in claim 1, wherein the gel forming additive is mineral oil present in an amount of 15 to 25 weight percent, based on the weight of the vinyl gel layer.

18. A device as claimed in claim 1, wherein the gel forming additive is silicone oil present in an amount of 10 to 25 weight percent, based on the weight of the vinyl gel layer.

19. The device according to claim 1, wherein the gel has a tensile strength of 500 psi or below.

20. The device according to claim 19, wherein the gel has a tensile strength below 350 psi.

21. The device according to claim 19, wherein the gel has a tensile strength below 150 psi.

22. The device according to claim 19, wherein the gel has a tensile strength below 75 psi.

23. The device according to claim 1, comprising about 5 to 25 weight percent nitroglycerin, about 30 to 50 weight percent PVC, about 25 to 50 weight percent of primary plasticizer, and about 5 to 20% of gel forming additive.

24. The device according to claim 23, wherein the primary plasticizer is dioctyl adipate and the gel forming additive is isopropyl palmitate.

25. A device according to claim 23, wherein the gel is opaque and has a tensile strength of 500 psi or below.

26. A device as claimed in claim 23, wherein the polyvinyl chloride is present in an amount of 43%, the primary plasticizer is present in an amount of 29%, the nitroglycerin is present in an amount of 8% and the gel forming additive is present in an amount of about 20%.

27. The device according to claim 1, wherein the gel has a tensile strength below 75 psi, an elongation at break below 25% and a tear strength of less than 30 lbs/inch.

28. A method for the transdermal delivery of nitroglycerin to a patient to provide said patient with nitroglycerin, comprising applying to said patient a device for the controlled release and delivery of nitroglycerin, the device comprising a vinyl gel layer and nitroglycerin uniformly dispersed in the layer in a pharmacologically effective amount, the vinyl layer comprising an emulsion polymerized polyvinyl chloride resin, a primary plasticizer for the polyvinyl chloride resin, and an organic, nonvolatile gel forming additive in an amount sufficient to form a gel.