Isotretinoin oral-mucosal formulations and methods for using same

Abstract

Disclosed herein, in part, is a pharmaceutical formulation comprising isotretinoin or a pharmaceutically acceptable salt thereof, and a mucoadhesive polymer. A method of treating a mucosal disease comprising administering a disclosed pharmaceutical formulation to a subject in need thereof is also provided herein.

1 . An oral adhesive pharmaceutical film comprising:
 a mucoadhesive layer comprising about 0.05% w/w to about 0.5% w/w isotretinoin or a pharmaceutically acceptable salt thereof, a vinylpyrrolidone-vinyl acetate co-polymer and a polyvinylpyrrolidone (PVP); and   an occlusive backing layer.   
     
     
         2 . The oral adhesive pharmaceutical film of  claim 1 , wherein the PVP has a weight average molecular weight of about 70,000 g/mol to about 1,600,000 g/mol. 
     
     
         3 . The oral adhesive pharmaceutical film of  claim 1 , wherein the vinylpyrrolidone-vinyl acetate co-polymer has a weight average molecular weight of about 45,000 g/mol to about 70,000 g/mol. 
     
     
         4 . The oral adhesive pharmaceutical film of  claim 1 , wherein the mucoadhesive layer comprises about 0.3% w/w isotretinoin. 
     
     
         5 . The oral adhesive pharmaceutical film of  claim 1 , wherein the mucoadhesive layer comprises about 0.2% w/w isotretinoin. 
     
     
         6 . The oral adhesive pharmaceutical film of  claim 1 , wherein the mucoadhesive layer further comprises propylene glycol (PG) and a polyethylene glycol (PEG). 
     
     
         7 . The oral adhesive pharmaceutical film of  claim 6 , wherein the PEG is PEG 400. 
     
     
         8 . The oral adhesive pharmaceutical film of  claim 1 , wherein the occlusive backing layer comprises a polymer selected from the group consisting of poly(methacrylic acid-co-ethylacrylate) 1:1, poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) 1:2:0.2, and combinations thereof. 
     
     
         9 . A layered pharmaceutical formulation for mucosal administration comprising: (1) a first layer comprising about 0.05% w/w to about 0.5% w/w isotretinoin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer; and (2) a second layer comprising an ingestible backing film. 
     
     
         10 . The multilayered pharmaceutical formulation of  claim 9 , wherein the second layer comprises a methacrylate-based co-polymer. 
     
     
         11 . A mucosal adhesive pharmaceutical film comprising: a mucoadhesive layer comprising about 0.1%-0.3% w/w isotretinoin or a pharmaceutically acceptable salt thereof, about 12% w/w to about 15% w/w vinylpyrrolidone-vinyl acetate copolymer, about 53% w/w to about 57% w/w PVP, about 16% w/w to about 19% w/w PEG 400 and about 4% w/w to about 6% w/w propylene glycol; and an occlusive backing layer. 
     
     
         12 . The mucosal adhesive pharmaceutical film of  claim 11 , wherein the occlusive backing layer comprises about poly(methacrylic acid-co-ethylacrylate) 1:1, poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) 1:2:0.2, PEG 400 and propylene glycol.