Method and Formulation for Improving Roflumilast Skin Penetration Lag Time

Abstract

Decreasing skin penetration lag times will improve the bioavailability of a topically administered roflumilast composition. A shorter skin penetration lag time provides quicker onset of disease relief and more consistent bioavailability as there is less transference to clothing or other people. The skin penetration lag time for roflumilast can be reduced by formulating a roflumilast composition to have a pH between 4.0 - 6.5 and/or combining roflumilast with an emulsifier blend comprising cetearyl alcohol, dicetyl phosphate and ceteth-10 phosphate.

1 . A method of treating a patient suffering from inflammatory dermatoses comprising:
 administering a topical pharmaceutical composition comprising roflumilast and an emulsifier blend, wherein the emulsifier blend comprises cetearyl alcohol, dicetyl phosphate and ceteth-10 phosphate, and   wherein said composition has a pH less than 7.5.   
     
     
         2 . The method of  claim 1 , wherein the composition comprises roflumilast in an amount of 0.05%-1% w/w. 
     
     
         3 . The method of  claim 2 , wherein the composition has a pH between 4.0 and 6.5. 
     
     
         4 . The method of  claim 3 , wherein the composition has a pH between 5.0 and 6.0. 
     
     
         5 . The method of  claim 3 , wherein the roflumilast has a skin penetration lag time of less than 1 hour. 
     
     
         6 . The method of  claim 5 , wherein 1 hour after administration, said roflumilast has a concentration in said patient’s plasma of at least 0.1 ng/mL. 
     
     
         7 . The method of  claim 6 , wherein 1 hour after administration, said roflumilast has a concentration in said patient’s plasma of at least 0.3 ng/mL. 
     
     
         8 . The method of  claim 4 , wherein the roflumilast has a skin penetration lag time of less than 1 hour. 
     
     
         9 . The method of  claim 8 , wherein 1 hour after administration, said roflumilast has a concentration in said patient’s plasma of at least 0.1 ng/mL. 
     
     
         10 . The method of  claim 9 , wherein 1 hour after administration, said roflumilast has a concentration in said patient’s plasma of at least 0.3 ng/mL. 
     
     
         11 . The method of  claim 1 , wherein the emulsifier blend is present in an amount sufficient to reduce roflumilast skin penetration lag time relative to the same composition without said emulsifier blend. 
     
     
         12 . The method of  claim 6 , wherein the composition comprises the emulsifier blend in an amount of 10% w/w. 
     
     
         13 . The method of  claim 2 , wherein the composition further comprises diethylene glycol monoethyl ether and water. 
     
     
         14 . The method of  claim 13 , wherein the composition comprises diethylene glycol monoethyl ether in an amount of 25% w/w. 
     
     
         15 . The method of  claim 13 , wherein the composition has a pH between 4.0 and 6.5. 
     
     
         16 . The method of  claim 15 , wherein the composition has a pH between 5.0 and 6.0. 
     
     
         17 . The method of  claim 15 , wherein the composition is configured to achieve a skin penetration lag time of roflumilast of less than 1 hour. 
     
     
         18 . The method of  claim 17 , wherein 1 hour after administration said roflumilast has a concentration in said patient’s plasma of at least 0.1 ng/mL. 
     
     
         19 . The method of  claim 18 , wherein 1 hour after administration said roflumilast has a concentration in said patient’s plasma of at least 0.3 ng/mL. 
     
     
         20 . The method of  claim 16 , wherein the roflumilast has a skin penetration lag time of less than 1 hour. 
     
     
         21 . The method of  claim 20 , wherein 1 hour after administration said roflumilast has a concentration in said patient’s plasma of at least 0.1 ng/mL. 
     
     
         22 . The method of  claim 21 , wherein 1 hour after administration said roflumilast has a concentration in said patient’s plasma of at least 0.3 ng/mL. 
     
     
         23 . The method of  claim 1 , wherein the patient is suffering from psoriasis. 
     
     
         24 . A method of treating a patient suffering from inflammatory dermatoses comprising:
 administering a topical pharmaceutical cream composition comprising roflumilast in an amount sufficient to treat said inflammatory dermatoses, diethylene glycol monoethyl ether and water, and   wherein said composition has a pH between 5.0 and 6.0.   
     
     
         25 . The method of  claim 24 , wherein the roflumilast has a skin penetration lag time of less than 1 hour. 
     
     
         26 . The method of  claim 24 , wherein 1 hour after administration said roflumilast has a concentration in said patient’s plasma of at least 0.1 ng/mL. 
     
     
         27 . The method of  claim 25 , wherein 1 hour after administration said roflumilast has a concentration in said patient’s plasma of at least 0.3 ng/mL.