Crystal forms of tetrahydro-n,n-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride, processes of making such forms, and their pharmaceutical compositions
Inventors
Daintree, Linda Sharon • Ledger, Daniel Mark • Leonard, Lucy Anne • York, Peter • Selvey, Alani
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11661405-B2
Publication Date
2023-05-30
Expiration Date
Abstract
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 (ANAVEX2-73) 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).
Core Innovation
The disclosure provides polymorphic crystalline forms of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73), including crystalline Form I, crystalline Form II, and crystalline Form III, and also covers the metabolite ANAVEX19-144. The polymorphs and the metabolite are characterized using PXRD, FTIR, 1H-NMR, and SEM, including particle habit and particle size. Stability of the crystalline forms after storage is also described, including PXRD after storage.
The disclosure further states that crystalline Form I, Form II, and Form III of ANAVEX2-73 are made by crystallizing ANAVEX2-73 in a supercritical fluid (SCF) environment. In the SCF environment, the supercritical fluid comprises supercritical carbon dioxide. The process yields specific polymorphs and particle morphologies, including particle habit such as plate-like, needle-like, lath-like, and conglomerate, and particle size.
The document describes that the SCF anti-solvent precipitation approach uses solvents to form a solution of ANAVEX2-73 prior to crystallization in the SCF environment, with solvent options including ethanol, acetonitrile, ethanol/trifluoroethanol mixtures, acetone/ethanol mixtures, and additional listed solvents. The disclosure includes examples and tables of process conditions for Forms I–III and provides characterization of ANAVEX19-144, including stability testing and improved powder flow for certain solvent-derived forms. The disclosure also links the crystalline forms to use in treating Alzheimer’s disease through neuroprotective treatment.
Claims Coverage
The provided independent claim covers making crystalline Form I, Form II, or Form III of ANAVEX2-73 by crystallizing ANAVEX2-73 in an SCF environment where the SCF comprises supercritical carbon dioxide. Three dependent claims refine the independent claim by adding a solvent-solution workflow, specifying solvent options and solvent mixtures, and constraining SCF pressure and temperature ranges.
Supercritical carbon dioxide environment for crystallizing ANAVEX2-73 polymorphs
A method of making crystalline Form I, Form II or Form III of ANAVEX2-73 by crystallizing ANAVEX2-73 in a supercritical fluid (SCF) environment in which the supercritical fluid comprises supercritical carbon dioxide.
Solvent solution introduction and crystal isolation workflow
Making the crystalline Form I, Form II or Form III by preparing ANAVEX2-73 into a solvent solution, introducing the solvent solution into the SCF, crystallizing to form crystals, and isolating the crystals to obtain the specified crystal Form I, Form II, or Form III.
Defined solvent selection for the ANAVEX2-73 solution
Using a solvent comprising one or more of the listed solvents, including ethanol, acetonitrile, isopropyl alcohol, trifluoroethanol, acetone, 2-ethoxyethanol, 1-propanol, dichloromethane, dimethyl sulfoxide, N,N′-dimethylacetamide, dimethylformamide, 3-methyl-1-butanol, N-methyl-2-pyrrolidone, tert-butanol, or combinations thereof, for preparing the ANAVEX2-73 solvent solution.
SCF pressure and temperature constraints
Crystallizing in an SCF environment having pressure from about 85 bar to about 200 bar and a temperature ranging from about 40°C.
Overall, the claim set centers on producing ANAVEX2-73 polymorphic crystalline Forms I–III by SCF crystallization using supercritical carbon dioxide, with dependent claims further specifying a solvent-solution introduction and crystal isolation workflow, defined solvent options for preparing the solution, and explicit SCF pressure and temperature constraints.
Stated Advantages
Improved powder flow for certain solvent-derived forms.
Documented Applications
Use in treating Alzheimer’s disease (neuroprotective treatment) with the described crystalline forms.
Interested in licensing this patent?