Formulation for lipophilic agents

Abstract

The invention relates to pharmaceutical formulations of lipophilic therapeutic agents in which such agents are solubilized in largely aqueous vehicles, and processes for preparing and using the same.

1 . A formulation, comprising a vitamin D compound; a non-ionic solubilizer selected from the group consisting of polyoxyalkylenes, polysorbate 20, fatty acid esters of glycerol, cyclodextrins, dextrans, and fatty alcohol ethers of oligoglucosides; a lipophilic antioxidant selected from the group consisting of butylated hydroxytoluene (BHT), lipoic acid, lycopene, lutein, lycophyll, xanthophyll, carotene, zeaxanthin, vitamin E and esters thereof; and an aqueous vehicle. 
   
   
       2 . A formulation as set forth in  claim 1 , wherein the lipophilic antioxidant is present in a concentration of 20 to 2000 ppm. 
   
   
       3 . A formulation as set forth in  claim 1 , wherein the non-ionic solubilizer is present in a concentration of 0.05 to 5% w/w. 
   
   
       4 . A formulation as set forth in  claim 1 , wherein the formulation is suitable for parenteral administration. 
   
   
       5 . A formulation as set forth in  claim 1 , further comprising an optional agent which is an organic solvent, a preservative or both. 
   
   
       6 . A formulation as set forth in  claim 5 , wherein the optional agent includes benzyl alcohol and ethanol. 
   
   
       7 . A formulation as set forth in  claim 6 , wherein the optional agent includes ethanol. 
   
   
       8 . A formulation as set forth in  claim 6 , wherein the optional agent includes benzyl alcohol. 
   
   
       9 . A formulation as set forth in  claim 6 , wherein the optional agent is present in a concentration of 0 to 30% w/w. 
   
   
       10 . A formulation as set forth in  claim 9 , wherein the optional agent is present in a concentration of 0% to about 10% w/w. 
   
   
       11 . A formulation as set forth in  claim 10 , wherein the optional agent is present in a concentration of about 1% to about 3% w/w. 
   
   
       12 . The formulation of  claim 1 , wherein the vitamin D compound is selected from the group consisting of 1α,24-dihydroxyvitamin D 2 , 1α,24-dihydroxyvitamin D 4 , 1α,25-dihydroxyvitamin D 3 , 1α-hydroxyvitamin D 3 , 1α, 25-dihydroxyvitamin D 2 , 1α,25-dihydroxyvitamin D 4 , and 1α,24,25-dihydroxyvitamin D 2 , seocalcitol, calcipotriol, maxacalcitol, falecalcitriol, paricalcitol. 
   
   
       13 .- 25 . (canceled) 
   
   
       26 . A parenteral formulation, comprising a vitamin D compound, 0.05 to 5% w/w of a non-ionic solubilizer non-ionic selected from the group consisting of polyoxyalkylenes, polysorbate 20, fatty acid esters of glycerol, cyclodextrins, dextrans, and fatty alcohol ethers of oligoglucosides; and 20 to 2000 ppm of a lipophilic antioxidant selected from the group consisting of butylated hydroxytoluene (BHT), lipoic acid, lycopene, lutein, lycophyll, xanthophyll, carotene, zeaxanthin, vitamin E and esters thereof. 
   
   
       27 . A formulation as set forth in  claim 26 , further comprising an optional agent. 
   
   
       28 . A formulation as set forth in  claim 27 , wherein the non-ionic solubilizer includes 0.5%-2.5% w/w polysorbate-20, the lipophilic antioxidant includes 20 ppm BHT and the optional agent includes 2.5% w/w ethanol. 
   
   
       29 . A formulation as set forth in  claim 27 , wherein the non-ionic solubilizer includes 0.5%-2.5% w/w polysorbate 20, the lipophilic antioxidant includes 20 ppm BHT and the optional agent includes 2.5% w/w benzyl alcohol. 
   
   
       30 .- 45 . (canceled)