Psilocin Salt And Cocrystal Forms for Stable Aqueous Dosing
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Solution Overview
Problem
Psilocin has limited stability and solubility in aqueous solutions, leading to variable effects and slow onset of therapeutic action, making it difficult to administer accurate doses, especially for intravenous use, and there is a need for formulations suitable for microdosing.
Innovation Solution
Development of crystalline forms of psilocin salts or cocrystals with coformers such as acetic acid, benzenesulfonic acid, and butyric acid, which exhibit improved solubility and stability, allowing for stable formulations for oral, subcutaneous, and intravenous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If psilocin is administered orally, then it can be given in a simple dosage form, but the absorption is variable and onset of action is slow
Solution Approach 1:
The patent changes the physical-chemical parameters of psilocin by converting it into different salt forms (hydrochloride, sulfate, phosphate, etc.) and cocrystal forms with various coformers. These parameter changes in molecular structure and crystalline arrangement improve solubility and dissolution rate, leading to more predictable and reliable plasma concentrations while maintaining ease of oral administration
2Speed
If psilocin is formulated for intravenous administration, then faster onset of action and standardized plasma concentrations can be achieved, but the formulation complexity increases due to solubility requirements
Solution Approach 1:
The patent applies parameter changes by developing psilocin salts and cocrystals with enhanced solubility properties. This allows the formulation of intravenous solutions without requiring complex delivery systems or extreme pH conditions, thereby achieving fast onset of action while keeping formulation complexity manageable
Solution Approach 2:
The patent uses salt-forming acids (hydrochloric acid, sulfuric acid, phosphoric acid) and cocrystal coformers as intermediary substances that facilitate the solubility of psilocin in aqueous media. These intermediaries enable intravenous formulation by mediating between the poorly soluble psilocin base and the required aqueous solubility for injection
3Ease of operation
If psilocin is stored in aqueous solution, then it can be prepared for injection, but stability is poor and rapid degradation occurs
Solution Approach 1:
The patent changes the chemical parameter of psilocin by converting it into stable salt and cocrystal forms. These modified forms exhibit significantly improved stability in aqueous solutions compared to the free base, allowing preparation of injectable solutions that remain stable during storage and administration
Solution Approach 2:
The patent applies beforehand cushioning by pre-formulating psilocin into stable salt and cocrystal forms that are resistant to degradation. This prior protection against chemical instability allows the substance to withstand storage in aqueous solutions without rapid degradation, ensuring stability before and during administration
4Quantity of substance
If microdoses of psilocin are administered, then lower quantities can be given for maintenance therapy, but accurate dosing becomes more difficult
Solution Approach 1:
The patent changes the solubility parameter of psilocin through salt and cocrystal formation, enabling accurate measurement and delivery of microdoses. The improved solubility allows precise formulation of low-dose preparations, ensuring accurate dosing even at maintenance therapy levels
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 solubility, stability, and reduced interindividual variability, enabling faster onset of action and standardized plasma concentrations, suitable for precise dosing and microdosing applications.
Implementation Method 1
Psilocin has limited stability and solubility in aqueous solutions... The crystalline forms provide enhanced solubility
Implementation Method 2
Crystalline or amorphous solid forms of a pharmaceutically active agents can exist as single-component and multiple-component solids... Different polymorphs may have differing properties such as stability
Data Source
AI summary
The present invention relates to crystalline forms of psilocin (4-hydroxy-N,N-dimethyltryptamine) salts or cocrystals, as well as compositions, methods of preparation and methods of their use. The present invention also relates to said crystalline forms having improved physical properties such as aqueous solubility and stability, wherein the crystalline forms and compositions thereof are suitable for oral, subcutaneous, intravenous, or intramuscular administration.