Therapeutic formulations of desoxyepothilones
Inventors
Licari, Peter J. • Zhong, Ziyang • Isaacs, Indu • Augustine, John G.
Assignees
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Publication Number
US-8618085-B2
Publication Date
2013-12-31
Expiration Date
Abstract
Formulations of desoxyepothilones are stable before and after dilution into aqueous media.
Core Innovation
The invention relates to pharmaceutically acceptable sterile concentrate formulations containing desoxyepothilones, notably epothilone D, and addresses poor aqueous solubility and degradation in water. The disclosed solution provides desoxyepothilone as a homogeneous solution using pharmaceutically acceptable carriers instead of CREMOPHOR® (polyethoxylated castor oil).
The formulations provide homogeneous solutions of desoxyepothilone together with pharmaceutically acceptable carriers comprising alcohols, glycols, polyols, and surfactants. The carriers include ethanol and/or propylene glycol, glycerol, and PEG/PEG400, together with polysorbate 80 (Tween® 80) and/or Solutol® HS-15.
The concentrate formulations are described as chemically and physically stable for storage under ambient conditions, and they form homogeneous solutions upon dilution into aqueous media. Physical stability is defined by lack of precipitation, crystallization, or phase separation, and chemical stability is defined by retention of at least 95% purity after dilution into aqueous medium.
Claims Coverage
The independent claims are clm-00001, clm-00006, and clm-00011. Each independent claim requires a homogeneous solution of a desoxyepothilone in a defined pharmaceutically acceptable carrier, with specified carrier component ranges, specified desoxyepothilone concentration ranges, and physically and chemically stable solutions before and after dilution into aqueous medium.
Homogeneous ethanol/glycerol/PEG400/polysorbate 80 desoxyepothilone solutions
A pharmaceutical composition providing a homogeneous solution of a desoxyepothilone with a pharmaceutically acceptable carrier comprising ethanol, glycerol, PEG 400, and polysorbate 80, with desoxyepothilone present at about 0.1 mg/mL to about 100 mg/mL, wherein the composition provides physically and chemically stable solutions before and after dilution into aqueous medium.
Homogeneous ethanol/propylene glycol/PEG400/polysorbate 80 desoxyepothilone solutions
A pharmaceutical composition providing a homogeneous solution of a desoxyepothilone with a pharmaceutically acceptable carrier comprising ethanol, propylene glycol, PEG400, and polysorbate 80, with desoxyepothilone present at about 1 mg/mL to about 100 mg/mL, wherein the composition provides physically and chemically stable solutions before and after dilution into aqueous medium.
Homogeneous ethanol/PEG400/Solutol HS-15 desoxyepothilone solutions
A pharmaceutical composition providing a homogeneous solution of a desoxyepothilone with a pharmaceutically acceptable carrier comprising ethanol, PEG400, and Solutol HS-15, with desoxyepothilone present at about 1 mg/mL to about 100 mg/mL, wherein the composition provides physically and chemically stable solutions before and after dilution into aqueous medium.
Across the independent claims, the main inventive features are homogeneous desoxyepothilone solutions formulated with specified ethanol/PEG/glycol/polyol and surfactant carriers, together with required physical and chemical stability before and after dilution into aqueous medium. Dependent claims further narrow the desoxyepothilone to epothilone D and specify sub-ranges, including examples such as about 10 mg/mL.
Stated Advantages
Provides physically stable solutions before and after dilution into aqueous medium.
Provides chemically stable solutions before and after dilution into aqueous medium.
Avoids reliance on CREMOPHOR® (polyethoxylated castor oil), which can cause patient discomfort/toxicity.
Documented Applications
Dilution into aqueous medium prior to administration, with described aqueous diluents including water, saline, and aqueous dextrose.
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