Injectable PARP Inhibitor Cyclodextrin Complexes for Rapid Bioavailability
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Solution Overview
Problem
There are no approved injectable formulations of PARP inhibitors for oncological and non-oncological indications, and existing oral formulations have low bioavailability and slow absorption rates, making them unsuitable for emergency medical situations like hemorrhagic shock and septic shock.
Innovation Solution
Development of amorphous powdered pharmaceutical compositions comprising PARP inhibitors in inclusion complexes with cyclodextrins or derivatives, which enhance solubility and bioavailability, allowing for rapid administration via injection or infusion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If oral formulations of PARP inhibitors are used, then the drugs can be administered orally, but the bioavailability is low and absorption rate is slow
Solution Approach 1:
The patent changes the physical state of the PARP inhibitor from crystalline to amorphous form, and modifies the route of administration from oral to intravenous injection. This parameter change transforms the drug delivery system to achieve rapid bioavailability while maintaining ease of administration through simple injection protocols.
Solution Approach 2:
The patent introduces cyclodextrin as an intermediary substance that forms inclusion complexes with the PARP inhibitor. This intermediary mechanism enhances the solubility and bioavailability of the drug, allowing for rapid absorption when administered intravenously while maintaining the simplicity of the administration process.
2Speed
If injectable formulations are developed, then rapid administration is achieved, but water-solubility improvement is needed
Solution Approach 1:
The patent employs cyclodextrin as a solubilizing intermediary that forms inclusion complexes with the hydrophobic PARP inhibitor. This intermediary substance enables the drug to achieve high water-solubility, facilitating rapid intravenous administration without compromising the drug's therapeutic efficacy.
Solution Approach 2:
The patent creates a composite formulation by combining the PARP inhibitor with cyclodextrin in a specific ratio (1:5 to 1:4800 mass ratio). This composite material approach results in an amorphous inclusion complex that exhibits enhanced water-solubility and rapid dissolution properties, enabling fast administration.
3Productivity
If amorphous powder formulation is used, then dissolution rate increases, but formulation stability over time must be maintained
Solution Approach 1:
The patent uses cyclodextrin as a stabilizing intermediary that forms protective inclusion complexes with the amorphous PARP inhibitor. This intermediary substance prevents crystallization and degradation over time, maintaining formulation stability while preserving the high dissolution rate characteristics of the amorphous form.
Solution Approach 2:
The patent optimizes the mass ratio parameter of the PARP inhibitor to cyclodextrin inclusion complex within the range of 1:5 to 1:4800. This parameter optimization ensures that the formulation achieves rapid dissolution while maintaining stability over time, balancing the competing requirements of speed and stability.
4Adaptability or versatility
If PARP inhibitors are used for non-oncological indications, then treatment versatility is improved, but no approved injectable formulations exist
Solution Approach 1:
The patent develops a universal injectable formulation of PARP inhibitor-cyclodextrin inclusion complex that can be applied across multiple indications including oncological (ovarian cancer) and non-oncological (hemorrhagic shock, septic shock) conditions. This multi-functional formulation approach enables the same drug composition to treat different disease states, significantly improving adaptability and versatility.
Solution Approach 2:
The patent changes the formulation parameters by creating an amorphous inclusion complex with cyclodextrin in specific mass ratios (1:5 to 1:4800), which enables the drug to achieve rapid dissolution and high bioavailability. This parameter change facilitates the development of approved injectable formulations for both oncological and non-oncological indications, overcoming the current limitation of no approved injectable versions.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compositions provide rapid dissolution and high bioavailability, enabling effective treatment of hemorrhagic shock, septic shock, and cancer by ensuring quick absorption and therapeutic efficacy.
Implementation Method 1
an amorphous powder of an inclusion complex comprising one or more PARP inhibitors and a cyclodextrin (CD) or derivative thereof
Implementation Method 2
the pharmaceutical composition completely dissolves in an aqueous solution in less than about 10 minutes
Data Source
AI summary
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.