VERFAHREN ZUR HERSTELLUNG VON PHARMAZEUTISCHEN ZUSAMMENSETZUNGEN ENTHALTEND EPOTHILON-ANALOGA ZUR KREBSBEHANDLUNG

Formulating an epothilone analog (I) for parenteral administration, comprises: (A) dissolving the analog in tert-butanol and water; (B) primary drying at -10 - -40 EC; (C) secondary drying at 10 - 30 EC; and (D) packaging the lyophilized product in a first vial in combination with a second vial containing an equal mixture by volume of a nonionic surfactant and anhydrous ethanol. Formulating an epothilone analog of formula (I) or their salt, solvate or hydrate for parenteral administration, comprises: (A) dissolving (I) in a mixture of tert-butanol (50 vol.%) in water to form a solution; (B) primary drying at -10 - -40 EC under high vacuum of 50 - 300 millitorr for 24 - 96 hours to form lyophilized product; (C) secondary drying the resultant lyophilized product at 10 - 30 EC under high vacuum of 50 - 300 millitorr for 24 - 96 hours; and (D) packaging the lyophilized product in a first vial in combination with a second vial containing an equal mixture by volume of a nonionic surfactant and anhydrous ethanol. [Image] Q : M-CH(R 7>)(CH 3) or CH=C(R 7>); M : O, S, NR 8> or CR 9>R 1> 0>; R 1> - R 5>, R 7> and R 1> 1> - R 1> 5>alkyl, aryl (both optionally substituted), H or heterocyclo; R 1>+R 2>cycloalkyl; R 6>alkyl, aryl, heterocyclo (all optionally substituted) or H; R 8>H, alkyl (optionally substituted), R 1> 1>C=O, R 1> 2>OC=O or R 1> 3>SO 2; and R 9> and R 1> 0>H, halo, alkyl (optionally substituted), aryl, heterocyclo, hydroxy, R 1> 4>C=O or R 1> 5>OC=O. Independent claims are also included for: (1) A pharmaceutical preparation (II) comprising, in separate vials, lyophilized (I) and its solvent such that when the contents of the vials are combined, the resulting solution contains (I) (2 - 4 mg/ml). The solvent mixture comprises a mixture of about equal parts by volume of dehydrated ethanol and the nonionic surfactant; (2) Process for forming a pharmaceutical composition for parenteral administration; (3) Treating a patient involving administering to the patient by intravenous injection the (II); (4) Treating cancer involving intravenously and orally administering (I); (5) A pharmaceutical composition (III) for parenteral administration comprising (I), dehydrated alcohol and non-ionic surfactant; (6) Method of treating cancer in a patient previously experiencing neurotoxicity involving intravenously administering the composition diluted in a parenteral diluent as a weekly infusion in dose of less than 200 mg/m 2>; (7) Treating cancer in a patient involving