Compound 1 Co-Crystals for Shock-Safe Soluble Formulation
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Solution Overview
Problem
2-bromo-1-(3,3-dinitroazetidin-1-yl)ethanone (Compound 1) is prone to detonation by shock or impact, posing safety issues during storage, transport, and handling, and has low solubility in water, necessitating a non-explosive and more soluble form for therapeutic applications.
Innovation Solution
Development of co-crystals of Compound 1 with calcium chloride, pyridoxine HCl, thiamine HCl, ferric chloride, manganese chloride, zinc chloride, and other salts, characterized by specific XRPD patterns and thermal properties, enhancing stability and solubility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Compound 1 is used in its pure form, then it maintains chemical integrity and therapeutic activity, but it becomes prone to detonation by shock or impact creating safety issues
Solution Approach 1:
The patent applies composite materials by forming co-crystals of Compound 1 with various salts (calcium chloride, pyridoxine HCl, thiamine HCl, ferric chloride, manganese chloride, zinc chloride). These co-crystal structures combine the therapeutic properties of Compound 1 with the stabilizing effects of the salt components, creating a composite solid form that is non-explosive while maintaining chemical integrity and therapeutic activity.
Solution Approach 2:
The patent changes the physical and chemical parameters of Compound 1 by transforming it from a pure crystalline form into co-crystalline forms with different salts. This parameter change in the solid-state structure eliminates the explosive properties while preserving the molecular identity and therapeutic effects of Compound 1.
2Reliability
If Compound 1 is used in its pure form, then it maintains chemical integrity, but it has relatively low solubility in water affecting administration and use
Solution Approach 1:
The patent creates composite co-crystal structures where Compound 1 is combined with water-soluble salts. The co-crystal lattice incorporates these salt components that provide enhanced water solubility while the overall structure maintains the chemical integrity and therapeutic activity of Compound 1 through preserved molecular identity and crystallographic order.
Solution Approach 2:
The patent modifies the solubility parameter of Compound 1 by forming co-crystals with salts having different solubility characteristics. This parameter change in the solid-form structure enables improved water solubility while maintaining the essential chemical properties and therapeutic effectiveness of the active compound.
3Reliability
If co-crystals are formed with various salts, then solubility and stability are enhanced, but the complexity of formulation and characterization increases
Solution Approach 1:
The patent demonstrates multi-functionality by showing that Compound 1 can form co-crystals with multiple different salts (calcium chloride, pyridoxine HCl, thiamine HCl, ferric chloride, manganese chloride, zinc chloride), each providing similar benefits of enhanced stability and solubility. This universal approach allows selection based on specific therapeutic needs while maintaining consistent performance characteristics.
Solution Approach 2:
The patent uses spectroscopic characterization methods including IR spectroscopy, Raman spectroscopy, and NMR spectroscopy to detect and confirm the formation of co-crystals through changes in vibrational and magnetic properties. These spectral changes provide clear identification of co-crystal structures and their unique physical properties.
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 co-crystals provide a non-explosive form of Compound 1, improving safety and solubility, enabling effective therapeutic use as an anti-inflammatory, antioxidant, and radioprotectant.
Implementation Method 1
co-crystals of 2-bromo-1-(3,3-dinitroazetidin-1-yl)ethanone and methods of preparing and using the co-crystals
Implementation Method 2
there remains a need to create more water soluble forms of the compound to improve administration and use
Implementation Method 3
Compound 1 calcium chloride co-crystal is characterized by having an XRPD pattern comprising peaks at angles 2-theta of 10.8±0.2, 11.6±0.2, and 14.9±0.2 degrees
Implementation Method 4
Compound 1 calcium chloride co-crystal is characterized by having a DSC graph comprising an endothermic peak at about 136.2° C.
Implementation Method 5
Compound 1 calcium chloride co-crystal is characterized by having a TGA graph substantially as shown in FIG. 1C
Implementation Method 6
Compound 1 calcium chloride co-crystal is characterized by having an IR spectrum comprising peaks at wavenumbers of about 411±2, 450±2, 510±2, 551±2, 568±2, 654±2, 708±2, 724±2, 757±2, 790±2, 841±2, 871±2, 897±2, 926±2, 1009±2, 1097±2, 1116±2, 1191±2, 1214±2, 1253±2, 1285±2, 1308±2, 1339±2, 1369±2, 1414±2, 1438±2, 1462±2, 1567±2, 1586±2, 1644±2, 1679±2, 2956±2, 3005±2, 3020±2, and 3387±2 cm−1
Implementation Method 7
Compound 1 calcium chloride co-crystal is characterized by having an 1H NMR spectrum comprising peaks at chemical shifts of about 3.35, 4.28, 4.83, and 5.15 ppm
Data Source
AI summary
The present disclosure relates generally to crystals, and more specifically to co-crystals of RRx-001 or 2-bromo-1-(3,3-dinitroazetidin-1-yl)ethanone and methods of preparing and using the co-crystals to treat or prevent various diseases, disorders, and conditions.