Crystalline Psilocybin Derivatives for Accurate API Dosing
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Solution Overview
Problem
There is a need to obtain and characterize crystalline forms of active pharmaceutical ingredients (APIs) such as tryptamines and psychedelic drug compounds to improve chemical and physical properties, and to avoid inaccuracies in molecular weight calculations affecting dosing and potency.
Innovation Solution
The development of crystalline forms of 5-[(3-{2-[bis(propan-2-yl)azaniumyl]ethyl}-1H-indol-4-yl)oxy]-5-oxopentanoate, including solvates like 4-glutarato-N,N-diisopropyltryptamine methanol solvate (4-glutarato-DiPT·MeOH) and ethanol solvate (4-glutarato-N,N-DiPT·EtOH), and crystalline forms thereof, which are characterized by specific X-ray powder diffraction patterns and space groups, and their use in pharmaceutical compositions with excipients and other compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If crystalline forms of APIs are obtained and characterized, then measurement precision of molecular weight is improved, but device complexity and manufacturing complexity increase
Solution Approach 1:
The patent applies parameter changes by obtaining and characterizing multiple crystalline forms (polymorphs) of the API, each with distinct crystal lattice parameters (unit cell dimensions, space groups). This allows precise determination of molecular weight and physical properties while managing complexity through systematic characterization of specific crystalline forms rather than all possible forms.
Solution Approach 2:
The patent uses X-ray diffraction technology to replace complex mechanical characterization methods. By using X-ray crystallography, the molecular weight and crystal structure can be determined precisely without requiring complex mechanical measurements or multiple characterization techniques, thus improving measurement precision while managing overall complexity.
2Manufacturing precision
If crystalline forms of APIs are obtained and characterized, then manufacturing precision and chemical stability are improved, but loss of time and productivity decrease
Solution Approach 1:
The patent applies preliminary action by pre-characterizing the crystalline forms of the API before pharmaceutical development. By obtaining and characterizing the crystal structure, molecular weight, and physical properties in advance, the patent eliminates the need for time-consuming characterization during later development stages, thus improving manufacturing precision while reducing overall time loss.
3Reliability
If crystalline forms of APIs are obtained and characterized, then reliability of dosing and potency calculations is improved, but measurement precision requirements increase
Solution Approach 1:
The patent uses X-ray crystallography to replace less precise measurement methods for determining molecular weight. This technology provides highly accurate and reliable molecular weight data that directly improves the reliability of dosing and potency calculations, while the systematic approach to characterization manages the measurement precision requirements.
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 improved chemical and physical properties, enabling accurate molecular weight determination and effective treatment of psychological disorders, inflammation, pain, and neurological disorders by modulating neurotransmitter activity and neurogenesis.
Implementation Method 1
an x-ray powder diffraction (XRPD) pattern substantially similar to FIG. 3; and an X-ray powder diffraction pattern characterized by peaks at 8.3, 11.1, and 15.1°2θ±0.2°2θ
Implementation Method 2
crystalline forms of 5-[(3-{2-[bis(propan-2-yl)azaniumyl]ethyl}-1H-indol-4-yl)oxy]-5-oxopentanoate, including solvates such as methanol 5-[(3-{2-[bis(propan-2-yl)azaniumyl]ethyl}-1H-indol-4-yl)oxy]-5-oxopentanoate
Data Source
AI summary
The disclosure relates to forms of 5-[(3-{2-[bis(propan-2-yl)azaniumyl]ethyl}-1H-indol-4-yl)oxy]-5-oxopentanoate, including solvates such as methanol 5-[(3-{2-[bis(propan-2-yl)azaniumyl]ethyl}-1H-indol-4-yl)oxy]-5-oxopentanoate (also referred to as 4-glutarato-N,N-diisopropyltryptamine methanol solvate or 4-glutarato-DiPT·MeOH), and crystalline forms thereof such as crystalline form 1 of 4-glutarato-DiPT·MeOH and ethanol 5-[(3-{2-[bis(propan-2-yl)azaniumyl]ethyl}-1H-indol-4-yl)oxy]-5-oxopentanoate (4-glutarato-N,N-diisopropyltryptamine ethanol solvate or 4-glutarato-N,N-DiPT·EtOH), crystalline 4-glutarato-N,N-DiPT·EtOH, and crystalline forms thereof, including crystalline form 1 of 4-glutarato-N,N-DiPT·EtOH; and to pharmaceutical compositions containing them and to methods of treatment using them. The disclosure further relates to crystalline [3-[2-(methylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate (baeocystin), such as crystalline form 1 of baeocystin, and to pharmaceutical compositions containing crystalline baeocystin, such as crystalline form 1 of baeocystin, and to methods of treatment using it.