Tipifarnib Intravenous Formulation via Cyclodextrin Solubilization
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Solution Overview
Problem
Current oral administration of tipifarnib is problematic for cancer patients due to issues like impaired oral intake, tumoral obstruction, and adverse effects, necessitating an alternative administration route that provides similar clinical outcomes.
Innovation Solution
Development of an intravenous formulation of tipifarnib, either as a continuous or shorter-duration infusion, using a combination of tipifarnib, mannitol, and hydroxypropyl-β-cyclodextrin to ensure solubility and safety for intravenous administration, allowing for central vein infusion to avoid local irritation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If tipifarnib is administered orally, then it provides antitumor effects and inhibits farnesyltransferase, but it causes problems in cancer patients with impaired oral intake, tumoral obstruction, and adverse effects
Solution Approach 1:
The patent uses a cyclodextrin derivative (hydroxypropyl-beta-cyclodextrin) as an intermediary solubilizing agent to enable intravenous administration of tipifarnib. This mediator allows the drug to be dissolved in aqueous solutions for IV injection, bypassing the oral route problems while maintaining drug delivery reliability
2Adaptability or versatility
If tipifarnib is formulated for intravenous administration, then it provides an alternative route for patients unable to take oral medication, but tipifarnib has poor water solubility and rapidly hydrolyzes at neutral pH
Solution Approach 1:
The cyclodextrin derivative acts as a protective intermediary that encapsulates tipifarnib, preventing its rapid hydrolysis at neutral pH while maintaining solubility in aqueous IV solutions. This mediator stabilizes the drug composition during intravenous administration
Solution Approach 2:
The patent modifies the chemical environment by using cyclodextrin derivatives that create a stable microenvironment for tipifarnib at neutral pH, changing the physical-chemical parameters to prevent hydrolysis while maintaining solubility for intravenous injection
3Reliability
If tipifarnib is administered as intravenous infusion, then it avoids problems with oral intake, but the formulation must ensure adequate solubility and avoid local irritation at the infusion site
Solution Approach 1:
The cyclodextrin derivative serves as a protective intermediary that reduces the direct contact of tipifarnib with blood vessels and tissues, minimizing local irritation while enabling reliable intravenous delivery
Solution Approach 2:
The formulation adjusts pH and uses solubilizing agents to optimize the physical-chemical parameters of the infusion solution, reducing irritation potential while maintaining drug stability and solubility for reliable IV administration
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 intravenous formulation achieves comparable systemic exposure and clinical efficacy to oral administration, with no unusual adverse events, and provides a viable option for patients unable to take tipifarnib orally, ensuring effective treatment of conditions like acute myeloid leukemia and breast cancer.
Implementation Method 1
The formulation comprises tipifarnib, mannitol and hydroxypropyl-β-cyclodextrin
Implementation Method 2
The formulation comprises tipifarnib, mannitol and hydroxypropyl-β-cyclodextrin
Data Source
AI summary
This invention concerns novel formulations of tipifarnib, which is suitable for intravenous (IV) administration. The invention further concerns the use of such formulation and processes for preparing such formulations and methods of treating by administering said formulations.