Injectable formulations of PARP inhibitors and uses thereof
Inventors
Li, Xu • Zhou, Zhiguo • Kumar, Krishan • CAO, Chunyan
Assignees
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Publication Number
US-12383633-B1
Publication Date
2025-08-12
Expiration Date
Abstract
Described herein are injectable or infusible formulations of PARP inhibitors. In one aspect, the formulation comprises a PARP inhibitor and a cyclodextrin. The injectable or infusible PARP inhibitor-cyclodextrin formulation improves drug solubility, bioavailability, and therapeutic effectiveness. Also described herein are methods for treating oncological and non-oncological indications with injectable or infusible formulations of PARP inhibitors.
Core Innovation
The invention relates to injectable or infusible pharmaceutical compositions comprising poly-(ADP-ribose) polymerase (PARP) inhibitors formulated as an amorphous powder inclusion complex with a cyclodextrin (CD) derivative comprising sulfobutylether-β-cyclodextrin (SBE-β-CD). The inclusion complex is characterized by a mass ratio of olaparib to CD derivative of about 1:60 to about 1:1000, and the formulation is provided as an amorphous powdered pharmaceutical composition suitable for reconstitution into a pharmaceutically acceptable solution for injection or infusion.
A manufacturing approach is described in which olaparib is mixed with an aqueous solution of SBE-β-CD at the specified mass ratio to create a mixture of the olaparib and the CD derivative in an inclusion complex. The mixture is frozen and lyophilized to create the amorphous powdered pharmaceutical composition, which is then dissolvable with a pharmaceutically acceptable solution for injection or infusion.
The described formulation is presented as enabling rapid aqueous dissolution and improved therapeutic availability by reducing water solubility limitations associated with PARP inhibitors. The document further supports that the formulation provides stability at room temperature, including at least about 3 years.
Claims Coverage
The independent claim set includes 4 independent claims covering composition, treatment method, method of making amorphous powder, and injectable/infusible composition made by a specified process. Across these claims, the core coverage includes forming an amorphous powdered inclusion complex of olaparib with SBE-β-CD at a defined olaparib-to-CD mass ratio range of about 1:60 to about 1:1000, and using freeze/lyophilize processing for a dissolvable injectable/infusible product for specified indications.
Amorphous powder inclusion complex composition with specified olaparib-to-SBE-β-CD ratio
A pharmaceutical composition comprising an amorphous powder of an inclusion complex comprising olaparib and a cyclodextrin (CD) derivative comprising sulfobutylether-β-cyclodextrin (SBE-β-CD) in a mass ratio of olaparib to CD derivative of about 1:60 to about 1:1000.
Treating shock or specified cancers by administering the inclusion-complex composition
A method of treating, ameliorating, or inhibiting the progress of hemorrhagic shock, septic shock, or ovarian, prostate, breast, or pancreatic cancer in a subject in need thereof, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising olaparib and SBE-β-CD in an inclusion complex and in a mass ratio of about 1:60 to about 1:1000.
Making amorphous powdered inclusion complex by mixing, freezing, and lyophilizing
A method of making an amorphous powdered pharmaceutical composition by mixing olaparib with an aqueous solution of SBE-β-CD at a mass ratio of about 1:60 to about 1:1000, freezing the mixture, and lyophilizing the frozen mixture to create the amorphous powdered pharmaceutical composition.
Injectable/infusible amorphous powdered inclusion complex with freeze/lyophilize and reconstitution
An injectable or infusible pharmaceutical composition made by mixing olaparib with an aqueous solution of SBE-β-CD at a mass ratio of about 1:60 to about 1:1000, freezing the mixture, lyophilizing the frozen mixture to create an amorphous powdered pharmaceutical composition, and dissolving the amorphous powdered pharmaceutical composition with a pharmaceutically acceptable solution for injection or infusion.
Across the independent claims, protection centers on an amorphous powdered inclusion complex of olaparib with SBE-β-CD at a defined mass ratio range of about 1:60 to about 1:1000, treatment of hemorrhagic shock, septic shock, and specified cancers by administering that inclusion-complex composition, and making injectable/infusible versions via mixing with aqueous SBE-β-CD, freezing, lyophilizing to form the amorphous powder, and dissolving with a pharmaceutically acceptable solution for injection or infusion.
Stated Advantages
Improved water solubility and rapid therapeutic availability as supported by rapid dissolution of olaparib-SBE-β-CD.
Long-term stability at room temperature, including at least about 3 years.
Complete aqueous dissolution in less than about 10 minutes.
Dissolved pharmaceutical composition is free of organic solvents.
Documented Applications
Treating, ameliorating, or inhibiting the progress of hemorrhagic shock and septic shock by administering a therapeutically effective amount of the specified injectable or infusible pharmaceutical composition.
Treating, ameliorating, or inhibiting the progress of ovarian cancer, prostate cancer, breast cancer, or pancreatic cancer by administering a therapeutically effective amount of the specified injectable or infusible pharmaceutical composition.
Use as an injectable or infusible pharmaceutical composition dissolved from the amorphous powdered inclusion complex with a pharmaceutically acceptable solution for injection or infusion.
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