Transdermal drug delivery device

Abstract

A diffusional drug delivery device is described which can provide for stability of the adhesive and system components, elimination of the initial burst of drug and hence irritation, and to provide for delayed onset of therapeutic effect along with delivery of a therapeutic agent at an optimum rate. The therapeutic agent in a first form which is suitable for storage, and the anhydrous activating means are inert when in an anhydrous environment. Moisture activates the system whereby the activating means provides an acidic or basic solution and the first form of the therapeutic agent is converted to a second form which is suitable for absorption through the skin or mucosa.

1. A controlled release medical device for delivery of at least one therapeutic agent in a pre-determined delivery rate pattern to a biological environment comprising, in combination:
 reservoir means containing a therapeutic agent which in a first form as a salt is suitable for storage and in a second form is a member selected from the group consisting of a free acid, a free base and an ester, is suitable for absorption through the skin or mucosa, and said reservoir means having a surface substantially impermeable to said therapeutic agent in said first form and permeable to said therapeutic agent in said second form and through which the second form of said therapeutic agent is released to the biological environment; and  
 activating means containing an activating agent wherein said activating agent in a first state is anhydrous, and in a second state is hydrated and in solution wherein said means is in the anhydrous form;  
 whereby the therapeutic agent is changed from its first to its second form by the activating means in its second state and whereby the passage of therapeutic agent to the biological environment by diffusion is impeded until the therapeutic agent changes form.  
 
     
     
       2. The device of  claim 1  wherein the activating means is moistened by cutaneous liquids, whereby said activating agent is changed from said first to said second state. 
     
     
       3. The device of  claim 1  wherein said reservoir means is a matrix having a therapeutic agent dispersed throughout, said means being substantially free of activating agent. 
     
     
       4. The device of  claim 3  wherein said activating means is a matrix having an activating agent dispersed throughout, said means being substantially free of therapeutic agent. 
     
     
       5. The device of  claim 4  which further comprises:
 rate controlling means for controlling the rate at which said activating means becomes hydrated when placed at its environment of use.  
 
     
     
       6. The device of  claim 4  which further comprises:
 rate controlling means for controlling the rate at which said activating agent in its second state diffuses into said reservoir means.  
 
     
     
       7. The device of  claim 1  wherein said reservoir means and said activating means comprise a single reservoir having a therapeutic agent and activating agent contained therein, in a dry blend. 
     
     
       8. The device of  claim 7  which further comprises:
 rate controlling means for controlling the rate at which said activating agent becomes hydrated.  
 
     
     
       9. The device of  claim 1  wherein said reservoir means and said activating means comprise a single reservoir having a therapeutic agent and activating agent contained therein, dispersed throughout a matrix. 
     
     
       10. The device of  claim 9  which further comprises:
 rate controlling means for controlling the rate at which said activating agent becomes hydrated.  
 
     
     
       11. The device of  claim 1  wherein said reservoir means is comprised of a therapeutic agent in a non-aqueous medium, said means being substantially free of activating agent. 
     
     
       12. The device of  claim 11  wherein said activating means is a matrix having an activating agent dispersed throughout, said means being substantially free of therapeutic agent. 
     
     
       13. The device of  claim 12  which further comprises:
 rate controlling means for controlling the rate at which activating agent in its second state diffuses into said reservoir means.  
 
     
     
       14. The device of  claim 1  wherein said reservoir means is comprised of a first and a second therapeutic agent which are codelivered. 
     
     
       15. The device of  claim 14  wherein said first and second therapeutic agents in a first form are salt forms of base drugs. 
     
     
       16. The device of  claim 14  wherein said first and second therapeutic agents in a first form are salt forms of acid drugs. 
     
     
       17. The device of  claim 14  wherein said first therapeutic agent is a non-salt drug and said second therapeutic agent in a first form is a salt form of a drug, and delivery of the second therapeutic agent is delayed until a change of state occurs. 
     
     
       18. The device of  claim 1  wherein said reservoir means is comprised of a first and a second therapeutic agent, where delivery of the second therapeutic agent commences when delivery of the first therapeutic agent ceases. 
     
     
       19. The device of  claim 18  wherein said first therapeutic agent in a first form is the salt form of an acid drug and said second therapeutic agent is the free form of a base drug. 
     
     
       20. The device of  claim 18  wherein said first therapeutic agent in a first form is the salt form of a base drug and said second therapeutic agent is the free form of an acid drug. 
     
     
       21. The device of  claim 1  wherein said therapeutic agent is selected from the group consisting of fluorouracil, barbitol, furosemide, albuterol, apomorphine, benzocaine, acetylsalicylic acid, scopolamine, clonidine, phenylpropanolamine, chlorpheniramine, pilocarpine, terbutaline, salbutamol, ephedrine, ergonovine, ergotamine, benztropine, nicotine, secoverine, propranolol and timolol. 
     
     
       22. A controlled release medical device for delivery of nicotine in a pre-determined delivery rate pattern to a biological environment comprising, in combination:
 reservoir means containing nicotine tartrate which is a form of nicotine suitable for storage, said nicotine tartrate being subsequently changed to nicotine which is suitable for absorption through the skin or mucosa, and said reservoir means having a surface substantially impermeable to nicotine tartrate and permeable to nicotine and through which nicotine is released to the biological environment; and  
 activating means containing an activating agent wherein said activating agent in a first state is anhydrous, and in a second state is hydrated and in solution; and said activating means is in the anhydrous form  
 whereby nicotine tartrate is changed to nicotine by the activating means in its second state and whereby the passage of nicotine to the biological environment by diffusion is impeded until the nicotine tartrate changes form.  
 
     
     
       23. The device of  claim 22  wherein the biological environment is the skin and the device further comprises means for maintaining said device in nicotine transferring relationship to the skin. 
     
     
       24. The device of  claim 23  wherein said means for maintaining said device in nicotine transferring relationship to the skin comprises an adhesive layer forming the skin contacting surface of the device. 
     
     
       25. The device of  claim 22  further comprising rate- controlling means for controlling the rate at which said activating means becomes hydrated when placed in contact with skin.   
     
     
       26. The device of  claim 25  wherein said rate- controlling means comprises means for controlling the rate at which said hydrated activating means diffuses into said reservoir means, said rate - controlling means being disposed between the activating means and said reservoir means.   
     
     
       27. The device of  claim 26  further comprising an adhesive for maintaining said device in nicotine transferring relationship to the skin, said adhesive forming the skin contacting surface of the device. 
     
     
       28. The device of  claim 5  wherein the biological environment is the skin and the device further comprises means for maintaining said device in nicotine transferring relationship to the skin. 
     
     
       29. The device of  claim 28  wherein said means for maintaining said device in nicotine transferring relationship to the skin comprises an adhesive layer forming the skin contacting surface of the device. 
     
     
       30. The device of  claim 29  wherein said rate- controlling means comprises means for controlling the rate at which said hydrated activating means diffuses into said reservoir means, said rate - controlling means being disposed between the activating means and said reservoir means.   
     
     
       31. The device of  claim 30  further comprising an adhesive for maintaining said device in nicotine transferring relationship to the skin, said adhesive forming the skin contacting surface of the device.