Ionic Pharmaceutical Cocrystals via Mechanochemistry
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Solution Overview
Problem
Traditional co-crystallization methods face challenges in crystallizing compounds such as oils, chiral compounds, and scarce natural products, as they often result in oils or single crystals of pure components rather than multi-component solids, limiting their application in pharmaceutical development and structural characterization.
Innovation Solution
The method involves mechanochemistry, specifically neat milling of a solid and a liquid followed by dissolution in a solvent and slow evaporation, to form ionic or partially ionic co-crystals, which can then be used as seeds for bulk crystallization, facilitating the crystallization of compounds that are difficult to crystallize using standard techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional co-crystallization methods are used, then the process is simple, but the method fails to crystallize difficult-to-crystallize compounds such as oils, chiral compounds, and scarce natural products
Solution Approach 1:
The patent changes the physical state parameters of the components by using a solid compound and a liquid compound in specific phase states during co-crystallization. The solid compound is milled with the liquid compound, and the resulting mixture is dissolved in a solvent and crystallized by controlled evaporation, transforming the difficult-to-crystallize liquid or oily compounds into crystalline co-crystal structures.
Solution Approach 2:
The patent introduces a solvent as an intermediary medium to facilitate the co-crystallization process. The solvent dissolves the milled mixture of solid and liquid compounds, enabling uniform distribution and subsequent crystallization upon evaporation, which would not occur directly without the solvent intermediary.
2Manufacturing precision
If typical co-crystallization techniques are applied, then the procedure is straightforward, but the result is often oils or single crystals of pure components rather than multi-component solids
Solution Approach 1:
The patent performs preliminary milling of the solid and liquid compounds together before dissolution and crystallization. This preliminary mechanical mixing ensures intimate contact and uniform distribution of the components in the solid-liquid mixture, which is critical for obtaining multi-component co-crystals rather than pure single crystals or oils.
Solution Approach 2:
The patent utilizes phase transitions throughout the process: the liquid compound remains in liquid phase during milling, then both components are dissolved in a solvent, and finally crystallization occurs upon solvent evaporation. This controlled phase transition sequence enables the formation of multi-component crystalline structures.
3Adaptability or versatility
If standard solution-growth techniques are used, then the method is simple, but it cannot produce crystalline materials that are inaccessible through standard techniques
Solution Approach 1:
The patent replaces traditional solution-growth mechanical mixing with mechanochemistry - specifically, mechanical milling of the solid and liquid compounds. This mechanical action at the molecular level creates intimate mixing and activates co-crystallization, enabling access to crystalline materials that are inaccessible through conventional solution methods.
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
This approach effectively converts viscous liquids and oils into crystalline co-crystals suitable for X-ray diffraction, enabling the synthesis of bulk solids and providing a strategy for obtaining crystalline materials that are inaccessible through standard solution-growth techniques, with the co-crystals exhibiting improved physical and chemical properties.
Implementation Method 1
the acidic group interacts with the basic group to form intermolecular hydrogen bonds in the co-crystallized composition
Implementation Method 2
the co-crystallization of the first and second molecules occurs by adding a solvent to the mixture of the molecules and then evaporating the added solvent
Implementation Method 3
the mixing of the first and second molecules occurs through the utilization of mechanical force, such as milling
Data Source
AI summary
Embodiments of the present disclosure pertain to methods of forming a co-crystallized composition by mixing a first molecule in a solid phase with a second molecule in a liquid phase to form a mixture, and then co-crystallizing the mixture to form the co-crystallized composition in the form of a crystalline solid. The mixing of the first and second molecules may occur through the utilization of mechanical force, such as milling. The co-crystallization of the first and second molecules may occur by adding a solvent to the mixture of the molecules and then evaporating the added solvent. The methods may also include a step of utilizing the co-crystallized composition as seed crystals to grow additional co-crystallized compositions. Further embodiments of the present disclosure pertain to the formed co-crystallized compositions.