Patches, formulations, and associated methods for transdermal delivery of drugs

Abstract

The present invention is drawn to transdermal drug formulations, transdermal patches incorporating such formulations, as well as associated methods. The formulations can include about 0.3 wt % to about 5 wt % of a drug, such as risperidone, about 4 wt % to about 30 wt % water, about 10 wt % to about 40 wt % glycerol, about 0.5 wt % to about 6 wt % oleyl alcohol. Other co-solvents and/or additives can be present to achieve a 100 wt % formulation.

What is claimed is: 
     
         1 . A formulation for transdermal delivery of risperidone, comprising:
 from about 0.3 wt % to about 5 wt % risperidone,   from about 4 wt % to about 30 wt % water,   from about 10 wt % to about 40 wt % glycerol, and   from about 0.5 wt % to about 6 wt % oleyl alcohol.   
     
     
         2 . A formulation as in  claim 1 , further comprising from about 20 wt % to about 85 wt % of an additional solvent. 
     
     
         3 . A formulation as in  claim 1 , wherein the risperidone comprises about 0.5 wt % to about 3 wt % of the formulation. 
     
     
         4 . A formulation as in  claim 1 , wherein the risperidone comprises about 0.8 wt % to about 1.8 wt % of the formulation. 
     
     
         5 . A formulation as in  claim 1 , wherein the risperidone comprises about 2 wt % of the formulation. 
     
     
         6 . A formulation as in  claim 1 , wherein the water comprises about 5 wt % to about 25 wt % of the formulation. 
     
     
         7 . A formulation as in  claim 1 , wherein the water comprises about 6 wt % to about 15 wt % of the formulation. 
     
     
         8 . A formulation as in  claim 1 , wherein the glycerol comprises about 15 wt % to 37 wt % about of the formulation. 
     
     
         9 . A formulation as in  claim 1 , wherein the glycerol comprises about 20 wt % to about 35 wt % of the formulation. 
     
     
         10 . A formulation as in  claim 1 , wherein the oleyl alcohol comprises about 1 wt % to about 5 wt % of the formulation. 
     
     
         11 . A formulation as in  claim 1 , wherein the oleyl alcohol comprises about 2 wt % to about 4 wt % of the formulation. 
     
     
         12 . A formulation as in  claim 2 , wherein the additional solvent is includes propylene glycol. 
     
     
         13 . A formulation as in  claim 1 , wherein the formulation has a pH of about 7.0 to about 10. 
     
     
         14 . A formulation as in  claim 1 , wherein the formulation includes a compound selected from the group consisting of butylated hydroxytoluene (BHT) and edentate disodium (EDTA). 
     
     
         15 . A formulation as in  claim 1 , wherein the formulation includes a skin irritation reduction agent selected from the group consisting of a corticosteroid and an anti-inflammatory agent. 
     
     
         16 . A formulation as in  claim 1 , wherein the formulation has a viscosity of about 20,000 centipoises to about 200,000 centipoises. 
     
     
         17 . A formulation as in  claim 1 , incorporated in a transdermal patch. 
     
     
         18 . A transdermal patch for transdermal delivery of risperidone, comprising:
 a transdermal drug formulation incorporated into a transdermal patch, said transdermal drug formulation comprising from about 0.3 wt % to about 5 wt % risperidone, from about 4 wt % to about 30 wt % water, from about 10 wt % to about 40 wt % glycerol, and from about 0.5 wt % to about 6 wt % oleyl alcohol.   
     
     
         19 . A transdermal patch of  claim 18 , further comprising from about 20 wt % to about 85 wt % of additional solvent. 
     
     
         20 . A transdermal patch as in  claim 18 , wherein the transdermal patch has a formulation-skin contact area of from 2 cm 2  to 100 cm 2 . 
     
     
         21 . A transdermal patch as in  claim 18 , wherein the transdermal patch has a formulation-skin contact area of from 5 cm 2  to 60 cm 2 . 
     
     
         22 . A transdermal patch as in  claim 20 , wherein each square centimeter of the formulation-skin contact area generates a mean AUC of at least 20 ng·hr/ml when administered to at least 10 human adults for a 72 hour period of time. 
     
     
         23 . A transdermal patch as in  claim 20 , wherein each square centimeter of the formulation-skin contact area generates a mean AUC of at least 34 ng·hr/ml when administered to at least 10 human adults for a 72 hour period of time. 
     
     
         24 . A transdermal patch as in  claim 20 , wherein each square centimeter of the formulation-skin contact area generates a mean AUC of at least 50 ng·hr/ml when administered to at least 10 human adults for a 72 hour period of time. 
     
     
         25 . A transdermal patch as in  claim 20 , wherein the total quantity of risperidone in said transdermal patch per cm 2  of the transdermal drug formulation-skin contact area is less than 2 mg/cm 2 . 
     
     
         26 . A transdermal patch as in  claim 18 , wherein the transdermal patch includes a microporous non-rate-limiting membrane. 
     
     
         27 . A transdermal patch as in  claim 18 , wherein the transdermal patch is configured to deliver risperidone at therapeutically effective rates for a period of at least 48 hours. 
     
     
         28 . A method of treating schizophrenia, bipolar disorder, or other psychiatric disorder in a subject, comprising:
 applying to a transdermal drug formulation to a skin surface of a subject, said transdermal formulation comprising from about 0.3 wt % to about 5 wt % risperidone, from about 4 wt % to about 30 wt % water, from about 10 wt % to about 40 wt % glycerol, and from about 0.5 wt % to about 6 wt % oleyl alcohol and optionally about 20 wt % to about 85 wt % of additional solvent; and   maintaining said transdermal drug formulation in contact with said skin surface for a period of at least 48 hours.   
     
     
         29 . The method as in  claim 28 , wherein the applying step is by applying the transdermal drug formulation to the skin surface by way of a transdermal patch which includes the transdermal drug formulation. 
     
     
         30 . A formulation for transdermal delivery of risperidone, comprising:
 risperidone,   about 6 wt % to about 15 wt % water,   about 20 wt % to about 35 wt % glycerol,   about 40% to about 70% propylene glycol, and   about 2 wt % to about 4 wt % oleyl alcohol.   
     
     
         31 . A formulation as in  claim 30 , incorporated into a transdermal patch. 
     
     
         32 . The formulation as in  claim 30 , said formulation having a pH of about 7.0 to about 10. 
     
     
         33 . A formulation as in  claim 30 , wherein the risperidone is present at from about 0.5 wt % to about 3 wt %. 
     
     
         34 . A transdermal patch for transdermal delivery of risperidone, comprising:
 a transdermal drug formulation incorporated in a transdermal patch, wherein the transdermal drug formulation comprises about 0.5 wt % to about 3 wt % risperidone, about 6 wt % to about 15 wt % water, about 20 wt % to about 35 wt % glycerol, about 40% to about 70% propylene glycol, from about 2 wt % to about 4 wt % oleyl alcohol, and has a pH of about 7 to about 10.   
     
     
         35 . A transdermal patch for transdermal delivery of risperidone, comprising:
 a transdermal drug formulation incorporated in a transdermal patch, wherein the transdermal drug formulation comprises risperidone, about 6 wt % to about 15 wt % water, about 20 wt % to about 35 wt % glycerol, from about 2 wt % to about 4 wt % oleyl alcohol, and about 20 wt % to about 85 wt % of additional solvent.