Supercritical Fluid Crystallization of ANAVEX2-73 Polymorphs
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Solution Overview
Problem
There is a need for fully characterized, new polymorphic and derivative forms of drug molecules like tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride that offer improved bioavailability and stability for effective drug formulations, particularly for the treatment of Alzheimer's disease.
Innovation Solution
The development of crystalline forms of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride, including Forms I, II, and III, and their metabolite ANAVEX19-144, characterized by specific PXRD patterns, FTIR spectra, and particle shapes, produced using a supercritical fluid (SCF) technique, which allows for the creation of therapeutically effective dosage forms for Alzheimer's disease treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional formulation methods are used, then the drug can be formulated, but bioavailability and stability are insufficient
Solution Approach 1:
The patent applies parameter changes by transforming the drug substance from amorphous or poorly crystalline states to specifically defined crystalline polymorphs (Forms I, II, and III) with distinct PXRD patterns. This crystallization process changes the physical state and molecular arrangement parameters, resulting in improved stability while maintaining or enhancing bioavailability through controlled particle morphology and size distribution.
Solution Approach 2:
The patent utilizes phase transitions by employing supercritical fluid processing to transform the drug substance from solution phase through supersaturation to crystalline phase. This controlled phase transition enables the formation of specific polymorphic forms with optimized stability and bioavailability characteristics, resolving the contradiction between these two parameters.
2Reliability
If new polymorphic forms are developed, then bioavailability and stability improve, but characterization and development complexity increase
Solution Approach 1:
The patent applies preliminary action by pre-defining and characterizing specific polymorphic forms (Forms I, II, and III) with established PXRD patterns, FTIR spectra, and particle morphology characteristics before formulation development. This preliminary characterization creates clear identification criteria that simplifies subsequent quality control and manufacturing, reducing overall development complexity despite the initial effort to characterize multiple forms.
3Manufacturing precision
If supercritical fluid processing is used, then particle size and morphology are optimized, but process complexity increases
Solution Approach 1:
The patent applies parameter changes in the supercritical fluid process by optimizing pressure, temperature, and solvent composition parameters to control nucleation and crystal growth. These parameter adjustments enable precise control over particle size distribution and morphology (plate-like, needle-like, or lath-like habits) while managing process complexity through systematic parameter optimization rather than complex equipment modifications.
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 crystalline forms provide enhanced neuroprotective effects and improved stability, enabling effective treatment of Alzheimer's disease by optimizing bioavailability and stability through the SCF process, which manipulates particle size, morphology, and habit for improved therapeutic outcomes.
Implementation Method 1
produced using a supercritical fluid (SCF) technique
Implementation Method 2
The crystalline forms are further characterized by the particle shapes depicted in FIG. 2, FIG. 3, FIG. 7 or FIG. 11
Data Source
AI summary
Polymorphic forms of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73) and a metabolite of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX19-144) are disclosed and characterized. Compositions and method for treatment of Alzheimer's disease that includes the polymorphic forms and metabolite of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73).