Aqueous Pharmaceutical Formulations of ER-beta Selective Ligands

An aqueous pharmaceutical composition comprising:

• a) an ERβ selective ligand in an amount of from about 0.14 μg/mL to about 40 mg/mL;
• b) a solubilizer/complexant component comprising from about 0.00021% (w/v) to about 60% (w/v) of the pharmaceutical composition;
• and
• c) an optional pH adjusting component in a concentration of from about 8.75×10−7 N to about 1.0 N;
• wherein the ERβ selective ligand has the Formula I:
• wherein:
• R1 is hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms, trifluoroalkoxy of 1-6 carbon atoms, thioalkyl of 1-6 carbon atoms, sulfoxoalkyl of 1-6 carbon atoms, sulfonoalkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, a 5 or 6-membered heterocyclic ring having 1 to 4 heteroatoms selected from O, N or S, —NO2, —NR5R6, —N(R5)COR6, —CN, —CHFCN, —CF2CN, alkynyl of 2-7 carbon atoms, or alkenyl of 2-7 carbon atoms;
• wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluoroalkyl, trifluoroalkoxy, —COR5, —CO2R5, —NO2, CONR5R6, NR5R6 or N(R5)COR6;
• R2 and R2a are each, independently, hydrogen, hydroxyl, halogen, alkyl of 1-6 carbon atoms, alkoxy of 1-4 carbon atoms, alkenyl of 2-7 carbon atoms, or alkynyl of 2-7 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms;
• wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluoroalkyl, trifluoroalkoxy, —COR5, —CO2R5, —NO2, CONR5R6, NR5R6 or N(R5)COR6;
• R3, R3ax, and R4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, halogen, alkoxy of 1-4 carbon atoms, trifluoroalkyl of 1-6 carbon atoms, or trifluoroalkoxy of 1-6 carbon atoms;
• wherein the alkyl or alkenyl moieties are optionally substituted with hydroxyl, —CN, halogen, trifluoroalkyl, trifluoroalkoxy, —COR5, —CO2R5, —NO2, CONR5R6, NR5R6 or N(R5)COR6;
• R5, R6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms;
• X is O, S, or NR7;
• and
• R7 is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-10 carbon atoms, —COR5, —CO2R5 or —SO2R5;
• or a pharmaceutically acceptable salt thereof;
• or the Formula III:
• wherein:
• R11, R12, R13, and R14 are each, independently, selected from hydrogen, hydroxyl, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or halogen;
• R15, R16, R17, R18, R19, and R20 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, halogen, alkoxy of 1-6 carbon atoms, —CN, —CHO, phenyl, or a 5 or 6-membered heterocyclic ring having 1 to 4 heteroatoms selected from O, N or S;
• wherein the alkyl or alkenyl moieties of R15, R16, R17, R18, R19, or R20 may be optionally substituted with hydroxyl, CN, halogen, trifluoroalkyl, trifluoroalkoxy, NO2, or phenyl;
• wherein the phenyl moiety of R15, R16, R17, R18, R19, or R20 may be optionally mono-, di-, or tri-substituted with alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, halogen, hydroxyl, alkoxy of 1-6 carbon atoms, CN, —NO2, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl group, thio, alkylthio of 1-6 carbon atoms, alkylsulfinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkoxycarbonyl of 2-7 carbon atoms, alkylcarbonyl of 2-7 carbon atoms, or benzoyl;
• and
• wherein at least one of R11, R12, R13, R14, R17, R18, R19 or R20 is hydroxyl, or a pharmaceutically acceptable salt thereof.