Pharmaceutical compositions comprising timolol

Abstract

The present invention relates to pharmaceutical composition comprising the beta 1(β1)-receptor blocker timolol and a liquid vehicle comprising a semifluorinated alkane. The pharmaceutical composition of the present invention may be useful for topical administration, for example ophthalmic topical administration and for use in the treatment of glaucoma, increased intraocular pressure, ocular hypertension and/or a symptom associated therewith.

1 . A pharmaceutical composition comprising:
 (a) timolol and/or a pharmaceutically acceptable salt thereof and   (b) a liquid vehicle comprising a semifluorinated alkane.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the semifluorinated alkane has formula (II)
   CF 3 (CF 2 ) n (CH 2 ) m CH 3   (II),
   wherein   n is an integer from 3 to 7, and   m is an integer from 4 to 7.   
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the semifluorinated alkane is selected from the group consisting of 1-perfluorobutyl-pentane (CF 3 (CF 2 ) 3 (CH 2 ) 4 CH 3 ; F4H5) and 1-perfluorohexyl-octane (CF 3 (CF 2 )(CH 2 ) 7 CH 3 ; F6H8). 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the timolol and/or a pharmaceutically acceptable salt thereof is suspended in the liquid vehicle comprising the semifluorinated alkane. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the concentration of timolol as free base is from about 0.3 to about 2.5% (w/v). 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the concentration of timolol as free base is from about 0.5 to about 2.0% (w/v). 
     
     
         7 . The pharmaceutical composition of  claim 1 , comprising timolol in the form of timolol maleate. 
     
     
         8 . The pharmaceutical composition of  claim 4 , wherein at least about 90% of the suspended particles of timolol and/or a pharmaceutically acceptable salt thereof have a size of not more than about 15 μm. 
     
     
         9 . (canceled) 
     
     
         10 . A method for the treatment of glaucoma, increased intraocular pressure, ocular hypertension and/or a symptom associated therewith, in a patient in need thereof, comprising administering to said patient a pharmaceutical composition according to  claim 1 . 
     
     
         11 . The method according to  claim 10 , wherein the composition is administered to the eye of a subject up to four times daily. 
     
     
         12 . The method according to  claim 10 , wherein the pharmaceutical composition is administered in a dose volume per eye of from about 8 to about 15 μl. 
     
     
         13 . The method according to  claim 10 , wherein the semifluorinated alkane is 1-perfluorohexyl-octane (CF 3 (CF 2 ) 5 (CH 2 ) 7 CH 3 , F6H8). 
     
     
         14 . The pharmaceutical composition according to  claim 1 , further comprising a co-solvent. 
     
     
         15 . A kit comprising the pharmaceutical composition according to  claim 1  and a container for holding the pharmaceutical composition. 
     
     
         16 . The pharmaceutical composition of  claim 5 , wherein the concentration of timolol as free base is from about 0.5 to about 1.5% (w/v). 
     
     
         17 . The pharmaceutical composition of  claim 7 , wherein the composition comprises the timolol maleate at a concentration of from about 0.4 to about 3.4% (w/v). 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein the composition comprises the timolol maleate at a concentration of from about 0.68% to about 2.1% (w/v). 
     
     
         19 . The method according to  claim 10 , wherein the composition is administered to the eye of a subject once daily. 
     
     
         20 . The method according to  claim 10 , wherein the pharmaceutical composition is administered in a dose volume per eye of from about 10 to about 12 μl.