PARP Inhibitor Cyclodextrin Formulations for Rapid Injection
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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 water-solubility, leading to low bioavailability and slow absorption rates, which are unsuitable for emergency medical settings.
Innovation Solution
Development of amorphous powdered pharmaceutical compositions comprising PARP inhibitors in inclusion complexes with cyclodextrins or derivatives, such as sulfobutylether-β-cyclodextrin, to 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 conveniently, but the water-solubility is low leading to low bioavailability and slow absorption rates
Solution Approach 1:
The patent changes the physical state of the PARP inhibitor from crystalline to amorphous form, which fundamentally alters the dissolution properties and increases water solubility. This parameter change enables the drug to achieve rapid dissolution and high bioavailability while maintaining ease of administration through various dosage forms
Solution Approach 2:
The patent creates composite material systems by combining amorphous PARP inhibitors with specific excipients and solvents to formulate injectable compositions. These composite formulations enhance solubility and enable parenteral administration, thereby improving bioavailability while maintaining administrative convenience
2Ease of operation
If oral formulations of PARP inhibitors are used, then the drugs can be administered conveniently, but the absorption rate is slow making them unsuitable for emergency medical settings
Solution Approach 1:
The transformation to amorphous form fundamentally changes the dissolution kinetics, enabling rapid dissolution and fast absorption. This parameter change allows the drug to achieve therapeutic levels quickly, making it suitable for emergency settings while preserving ease of administration
Solution Approach 2:
The patent develops injectable formulations that deliver the drug directly into the bloodstream or tissue, bypassing the gastrointestinal absorption pathway. This hydraulic delivery method achieves immediate bioavailability and rapid onset of action, ideal for emergency medical situations
3Reliability
If injectable formulations are developed, then rapid effectiveness and high bioavailability can be achieved, but the water-solubility of PARP inhibitors must be improved first
Solution Approach 1:
The patent applies parameter changes by converting the crystalline PARP inhibitor to amorphous form, which dramatically improves water solubility. This enables the formulation of injectable compositions with high bioavailability while maintaining manufacturing feasibility through established amorphization techniques
Solution Approach 2:
The patent introduces solubilizing excipients and surfactants as intermediaries that enhance the water solubility of amorphous PARP inhibitors. These mediators facilitate the formation of stable, soluble injectable formulations without compromising the active ingredient's efficacy
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 with Tmax less than 10 minutes, suitable for emergency medical use.
Implementation Method 1
amorphous powder of an inclusion complex comprising one or more PARP inhibitors and a cyclodextrin (CD) or derivative thereof
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.