Crystalline Substrates for Controlled Polymorph Selection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods fail to reliably control and consistently obtain specific polymorphic forms of molecular species, particularly 'hard to crystallize' and computationally predicted forms that have not been observed experimentally, due to limitations in conventional polymorph screening techniques.
Innovation Solution
The use of crystalline substrates with complimentary space groups, unit cell dimensions, and functional groups to facilitate the crystallization of selected polymorphic forms, reducing the average induction time by a factor of at least three, by matching the substrate's parameters with the target polymorph and ensuring the substrate is insoluble in the solvent.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional polymorph screening techniques are used, then various polymorphic forms can be obtained, but reliable control and consistent obtainment of specific polymorphic forms cannot be achieved
Solution Approach 1:
The patent introduces a crystalline substrate as an intermediary that mediates the crystallization process. The substrate provides a pre-formed crystal lattice that acts as a template, guiding the molecular species to arrange themselves in the desired polymorphic configuration. This intermediary structure enables reliable control over which polymorphic form crystallizes from solution.
Solution Approach 2:
The patent applies preliminary action by pre-preparing crystalline substrates with specific crystal structures, space groups, and unit cell dimensions before the crystallization process. These pre-characterized substrates are then introduced to the molecular species solution, eliminating the need for trial-and-error screening and ensuring consistent production of the desired polymorph.
2Productivity
If conventional crystallization methods are used, then crystallization can occur, but the induction time for obtaining specific polymorphic forms is excessively long
Solution Approach 1:
The crystalline substrate serves as a mediator that provides a ready-made crystal lattice structure. This eliminates the time-consuming nucleation step where molecules must randomly arrange themselves, as the substrate already provides the correct spatial arrangement. The molecular species can directly deposit onto the substrate in the desired polymorphic form, dramatically reducing induction time.
Solution Approach 2:
The patent applies local quality by providing a localized crystalline environment on the substrate surface that differs from the bulk solution. The substrate surface creates a specific local structure with defined space group and unit cell dimensions, which guides the crystallization of the molecular species in the desired polymorphic form at that local site, accelerating the overall process.
3Reliability
If substrates without complimentary functional groups are used, then crystallization can occur, but the induction time is not reduced and polymorphic control is poor
Solution Approach 1:
The patent employs composite materials by combining the crystalline substrate with the molecular species in a way that creates a new crystalline composite structure. The substrate provides the structural framework with specific space group and unit cell dimensions, while the molecular species fills in the lattice positions, creating a composite crystal structure that exhibits the desired polymorphic properties.
Solution Approach 2:
The patent applies parameter changes by carefully selecting substrates with specific crystallographic parameters (space group, unit cell dimensions) and surface chemical parameters (functional groups) that match the desired polymorphic form. By changing these substrate parameters to be complimentary to the target polymorph, the patent achieves both reduced induction time and improved polymorphic control.
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 allows for the controlled crystallization of desired polymorphic forms, including 'disappearing' and computationally predicted forms, by enhancing nucleation kinetics and stabilizing pre-nucleation aggregates through epitaxial ordering and functional group interactions, thereby overcoming the limitations of conventional methods.
Implementation Method 1
causing the molecular species to crystallize in the selected polymorphic form on at least a portion of the template
Implementation Method 2
exposing a substrate comprising a crystalline template to a molecular species
Implementation Method 3
the template comprises on at least one surface comprising a plurality of complimentary functional groups to the functional groups of the molecular species
Data Source
AI summary
The present invention generally relates to methods and systems relating to the selection of substrates comprising crystalline templates for the controlled crystallization of molecular species. In some embodiments, the methods and systems allow for the controlled crystallization of a molecular species in a selected polymorphic form. In some embodiments, the molecular species is a small organic molecule (e.g., pharmaceutically active agent).