Fulvestrant formulation

Abstract

The invention relates to a novel sustained release pharmaceutical formulation adapted for administration by injection containing the compound 7α-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-triene-3,17β-diol, more particularly to a formulation adapted for administration by injection containing the compound 7α-[9(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra-1,3,5(10)-triene-3,17β-diol in solution in a ricinoleate vehicle which additionally comprises at least one alcohol and a non-aqueous ester solvent which is miscible in the ricinoleate vehicle.

1 . A pharmaceutical formulation comprising fulvestrant in a ricinoleate vehicle, a pharmaceutically acceptable non-aqueous ester solvent, and a pharmaceutically acceptable alcohol wherein the formulation is adapted for intramuscular administration and attaining a therapeutically significant blood plasma fulvestrant concentration for at least 2 weeks.  
     
     
         2 . A pharmaceutical formulation adapted for intramuscular injection comprising fulvestrant, 30% or less weight of a pharmaceutically-acceptable alcohol per volume of formulation, at least 1% weight of a pharmaceutically-acceptable non-aqueous ester solvent miscible in a ricinoleate vehicle per volume of formulation and a sufficient amount of a ricinoleate vehicle so as to prepare a formulation which is capable after injection of attaining a therapeutically significant blood plasma fulvestrant concentration for at least 2 weeks.  
     
     
         3 . A pharmaceutical formulation as claimed in  claim 1  or  2  wherein the blood plasma fulvestrant concentration attained is at least 2.5 ngml −1  for at least 2 weeks.  
     
     
         4 . A pharmaceutical formulation adapted for intra-muscular injection comprising fulvestrant, 30% or less weight of a pharmaceutically-acceptable alcohol per volume of formulation, at least 1% weight of a pharmaceutically-acceptable non-aqueous ester solvent miscible in a ricinoleate vehicle per volume of formulation and a sufficient amount of a ricinoleate vehicle so as to prepare a formulation of at least 45 mgml −1  of fulvestrant.  
     
     
         5 . A pharmaceutical formulation as claimed in  claim 1  to  4  which contains 25% w/v or less of a pharmaceutically-acceptable alcohol.  
     
     
         6 . A pharmaceutical formulation as claimed in  claim 5  which contains 20% w/v or less of a pharmaceutically-acceptable alcohol.  
     
     
         7 . A pharmaceutical formulation as claimed in any claim from  1  to  6  which contains 60% w/v or less of a pharmaceutically-acceptable non-aqueous ester solvent.  
     
     
         8 . A pharmaceutical formulation as claimed in  claim 7  which contains 50% w/v or less of a pharmaceutically-acceptable non-aqueous ester solvent.  
     
     
         9 . A pharmaceutical formulation as claimed in  claim 7  which contains 45% w/v or less of a pharmaceutically-acceptable non-aqueous ester solvent.  
     
     
         10 . A pharmaceutical formulation as claimed in  claim 7  which contains 40% w/v or less of a pharmaceutically-acceptable non-aqueous ester solvent.  
     
     
         11 . A pharmaceutical formulation as claimed in  claim 7  which contains 35% w/v or less of a pharmaceutically-acceptable non-aqueous ester solvent.  
     
     
         12 . A pharmaceutical formulation as claimed in  claim 7  which contains 30% w/v or less of a pharmaceutically-acceptable non-aqueous ester solvent.  
     
     
         13 . A pharmaceutical formulation as claimed in  claim 7  which contains 25% w/v or less of a pharmaceutically-acceptable non-aqueous ester solvent.  
     
     
         14 . A pharmaceutical formulation as claimed in any claim from  1  to  13  wherein the pharmaceutically-acceptable alcohol is a mixture of ethanol and benzyl alcohol.  
     
     
         15 . A pharmaceutical formulation as claimed in any claim from  1  to  14  wherein the pharmaceutically-acceptable non-aqueous ester solvent is selected from benzyl benzoate, ethyl oleate, isopropyl myristate, isopropyl palmitate or a mixture of any thereof.  
     
     
         16 . A pharmaceutical formulation as claimed in any claim from  1  to  15  wherein the pharmaceutically-acceptable non-aqueous ester solvent is benzyl benzoate.  
     
     
         17 . A pharmaceutical formulation as claimed in any claim from  1  to  16  wherein the total volume of the formulation is 6 ml, or less, and the concentration of fulvestrant is at least 45 mgml −1 .  
     
     
         18 . A pharmaceutical formulation as claimed in any claim from  1  to  13  wherein the total amount of fulvestrant in the formulation is 250 mg, or more, and the total volume of the formulation is 6 ml, or less.  
     
     
         19 . A pharmaceutical formulation as claimed in  claim 18  wherein the total amount of fulvestrant in the formulation is 250 mg and the total volume of the formulation is 5 to 5.25 ml.  
     
     
         20 . A pharmaceutical formulation as claimed in any of claims  1 - 19  wherein the pharmaceutically-acceptable alcohol is a mixture of 10% weight of ethanol per volume of formulation, 10% weight of benzyl alcohol per volume of formulation and 15% weight of benzyl benzoate per volume of formulation and the ricinoleate vehicle is castor oil.  
     
     
         21 . An pharmaceutical formulation adapted for intramuscular injection, as defined in any claim from  1  to  20 , for use in medical therapy.  
     
     
         22 . Use of fulvestrant in the preparation of a pharmaceutical formulation, as defined in any claim from  1  to  20 , for the treatment of a benign or malignant disease of the breast or reproductive tract.  
     
     
         23 . A syringe or vial containing a pharmaceutical formulation as defined in  claim 20.