IV Ticagrelor Cyclodextrin Formulation for Gram-Positive Bacteremia
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Solution Overview
Problem
Current ticagrelor formulations, particularly tablets, have limited bioavailability and are not suitable for intravenous administration due to solubility and stability issues, making them inadequate for treating Gram-positive bacteremia, especially in emergency situations.
Innovation Solution
Development of an aqueous ticagrelor solution with hydroxypropyl-beta-cyclodextrin inclusion complex, providing stable formulations with 100% bioavailability, suitable for intravenous administration, and storage stability of at least 3 months under specified conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ticagrelor is administered as tablets orally, then the treatment can be given to patients, but the bioavailability is limited to 36% with large variability between individuals
Solution Approach 1:
The patent introduces an intravenous formulation as an intermediary administration route that bypasses the limitations of oral absorption. By delivering ticagrelor directly into the bloodstream through intravenous injection or infusion, the formulation achieves 100% bioavailability and eliminates the variability associated with oral absorption, while maintaining ease of operation through standardized clinical administration protocols
Solution Approach 2:
The patent changes the administration parameter from oral to intravenous route, fundamentally altering how ticagrelor is delivered to the patient. This parameter change transforms the bioavailability from 36% (oral) to 100% (intravenous), providing reliable and consistent drug delivery while maintaining operational simplicity in clinical settings
2Reliability
If ticagrelor is formulated for intravenous administration, then bioavailability becomes 100% and variability decreases, but the formulation is challenging due to limited solubility and degradation susceptibility
Solution Approach 1:
The patent employs cyclodextrin as an intermediary solubilizing agent that forms inclusion complexes with ticagrelor molecules. This intermediary substance enables the hydrophobic ticagrelor to be dissolved in aqueous formulations, achieving 100% bioavailability through intravenous administration while overcoming the formulation challenges posed by ticagrelor's limited solubility
Solution Approach 2:
The patent converts the harmful effect of ticagrelor's degradation susceptibility into a benefit by implementing specific formulation conditions. By controlling pH, adding stabilizing agents, and optimizing storage conditions, the formulation maintains ticagrelor stability throughout the shelf life, transforming the vulnerability into a manageable characteristic that can be controlled through proper formulation design
3Loss of time
If ticagrelor solution is stored for extended periods, then availability for emergency use is improved, but storage stability deteriorates due to degradation from light, heat and oxygen
Solution Approach 1:
The patent applies preliminary protective measures during formulation development by incorporating stabilizing agents and optimizing the formulation composition before storage. These preliminary actions prevent degradation from occurring during storage, enabling extended storage duration while maintaining ticagrelor stability and composition integrity
Solution Approach 2:
The patent creates an inert protective environment for the ticagrelor solution by controlling storage conditions to minimize exposure to degrading factors. The formulation is designed to be stable under typical storage conditions, effectively creating a protected environment that prevents light, heat, and oxygen from degrading the ticagrelor, thereby enabling extended storage without loss of stability
4Reliability
If oral tablets are used for bacteremia treatment, then the treatment can be administered, but the treatment effectiveness is reduced due to limited and variable bioavailability
Solution Approach 1:
The patent introduces intravenous administration as an intermediary route that directly delivers ticagrelor to the bloodstream, eliminating the absorption barrier present in oral administration. This intermediary approach ensures treatment effectiveness by achieving 100% bioavailability and consistent drug levels, while maintaining ease of operation through standardized clinical protocols
Solution Approach 2:
The patent changes the administration parameter from oral to intravenous, fundamentally improving treatment effectiveness. This parameter change eliminates the variability in bioavailability associated with oral absorption, ensuring reliable and consistent drug delivery to the bloodstream for effective bacteremia treatment
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 solution ensures rapid and effective treatment of Gram-positive bacteremia with ticagrelor, maintaining stability and bioavailability, allowing direct administration into the bloodstream without prior adjustments, suitable for unconscious or swallowing-impaired patients.
Implementation Method 1
aqueous ticagrelor solution with hydroxypropyl-beta-cyclodextrin inclusion complex
Data Source
AI summary
The present invention relates to aqueous ticagrelor solutions provided for intravenous administration for use in the treatment of a Gram-positive bacterial infection in the blood stream of a patient in need thereof. The invention is advantageous to further improve the effectiveness of bacteremia treatments, especially for MSSA and MRSA bacteremia and bacteremia-associated thrombocytopenia.