Ceftolozane antibiotic compositions
Inventors
Terracciano, Joseph • Damour, Nicole Miller • Jiang, Chun • Fogliato, Giovanni • Donadelli, Giuseppe Alessandro • Resemini, Dario
Assignees
ACS Dobfar SpA • Cubist Pharmaceuticals LLC • Merck Sharp and Dohme LLC • Calixa Therapeutics Inc
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Publication Number
US-9872906-B2
Publication Date
2018-01-23
Expiration Date
Abstract
This disclosure provides pharmaceutical compositions comprising ceftolozane, pharmaceutical compositions comprising ceftolozane and tazobactam, methods of preparing those compositions, and related methods and uses of these compositions.
Core Innovation
The invention is directed to solid pharmaceutical compositions comprising ceftolozane sulfate and tazobactam sodium, wherein the ceftolozane active and tazobactam active are provided in a ratio of 2:1 by weight. The composition controls the level of impurities and related compounds during storage, including a compound of formula (III) and, in further embodiments, a compound of formula (IV).
The composition comprises less than 0.15% of a compound of formula (III) relative to ceftolozane sulfate, as determined by high performance liquid chromatography (HPLC) at a wavelength of 254 nm, when stored for 1 month at 25±5 C and 60% relative humidity. In other embodiments, the composition further limits a compound of formula (IV), also determined by HPLC at 254 nm, with the storage period extended to 3 months under the same temperature and relative humidity conditions.
The invention additionally includes embodiments in which the impurity is a compound characterized by the mass spectra depicted in FIG. 14, with the same HPLC at 254 nm and storage-condition framework. The disclosed pharmaceutical compositions include unit dosage forms and injectable compositions, including embodiments in which the composition is dissolved in a pharmaceutically acceptable vehicle.
Claims Coverage
The independent claims cover four claim directions centered on a ceftolozane sulfate/tazobactam sodium composition in a 2:1 by weight ratio, with quantitative limits on impurities or related compounds measured by HPLC at 254 nm after specified storage conditions. The main inventive features are control of formula (III), and in some claims additional control of formula (IV) or of a compound characterized by the mass spectra depicted in FIG. 14.
Impurity-controlled solid composition with formula (III) limit after 1 month storage
A solid pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium in a ratio of 2:1 by weight, wherein the composition comprises less than 0.15% of a compound of formula (III) relative to ceftolozane sulfate, as determined by HPLC at 254 nm, when stored for 1 month at 25±5 C and 60% relative humidity.
Impurity-controlled composition with formula (III) and formula (IV) limits after 3 month storage
A pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium in a ratio of 2:1 by weight, wherein the composition comprises less than 0.15% of a compound of formula (III) relative to ceftolozane sulfate and less than 1.5% of a compound of formula (IV) relative to ceftolozane sulfate, as determined by HPLC at 254 nm, when stored for 3 months at 25±5 C and 60% relative humidity.
FIG. 14 mass-spectra related compound limit after 1 month storage
A pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium in a ratio of 2:1 by weight, wherein the composition comprises less than 0.15% relative to ceftolozane sulfate of the compound having a mass spectra depicted in FIG. 14, as determined by HPLC at 254 nm, when stored for 1 month at 25±5 C and 60% relative humidity.
Impurity-controlled composition with FIG. 14 compound and formula (IV) limits after 3 month storage
A pharmaceutical composition comprising ceftolozane sulfate and tazobactam sodium in a ratio of 2:1 by weight, wherein the composition comprises less than 0.15% relative to ceftolozane sulfate of a compound having a mass spectra depicted in FIG. 14 as determined by HPLC at 254 nm, and less than 1.5% of a compound of formula (IV) relative to ceftolozane sulfate as determined by HPLC at 254 nm, when stored for 3 months at 25±5 C and 60% relative humidity.
Across the independent claims, coverage centers on a ceftolozane sulfate/tazobactam sodium composition with a 2:1 weight ratio and controlled levels of specific impurities or related compounds, including formula (III) and, in some embodiments, formula (IV) or a compound characterized by FIG. 14, with quantification by HPLC at 254 nm and storage durations of 1 month or 3 months at 25±5 C and 60% relative humidity.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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