Harmine Salt Formulations for Solubility and Mucosal Bioavailability
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Solution Overview
Problem
Existing formulations of harmine suffer from poor solubility and bioavailability, limiting their pharmaceutical applications, particularly in the development of highly bioavailable formulations or salts suitable for administration via routes other than the gastrointestinal tract.
Innovation Solution
Compositions comprising harmine or its pharmaceutically acceptable salts in combination with uronic acids or carboxylic acids and monosaccharides are developed to enhance solubility and bioavailability, including the use of carrier particles to mask bitterness during oral mucosal absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If harmine is formulated in traditional forms, then it maintains chemical stability, but it exhibits poor solubility and low bioavailability
Solution Approach 1:
The patent uses uronic acids (such as glucuronic acid, galacturonic acid, iduronic acid, and their derivatives) as intermediary substances to form co-crystals or salts with harmine. These intermediaries act as mediators that improve the solubility and bioavailability of harmine while maintaining its chemical stability, directly resolving the contradiction between stability and solubility
Solution Approach 2:
The patent creates composite materials by combining harmine with uronic acids to form new crystalline structures (co-crystals or salts). These composite materials exhibit both the chemical stability of harmine and the enhanced solubility properties of uronic acids, simultaneously achieving both desired properties
2Ease of operation
If harmine is administered via gastrointestinal tract, then it achieves systemic delivery, but it suffers from poor absorption and high subject-to-subject variability
Solution Approach 1:
The patent changes the physicochemical parameters of harmine by forming it into co-crystals or salts with uronic acids. This parameter change modifies the dissolution rate and absorption characteristics, enabling reliable non-gastrointestinal administration routes (such as oral mucosal, sublingual, or buccal routes) while maintaining consistent bioavailability and reducing subject-to-subject variability
3Quantity of substance
If harmine formulations are developed for rapid absorption, then bioavailability improves, but bitterness and other adverse effects increase
Solution Approach 1:
The uronic acid co-crystals or salts serve as intermediaries that mask the bitter taste of harmine. The uronic acid component acts as a taste-modifying intermediary, allowing rapid absorption and high bioavailability while reducing the perception of bitterness and other adverse sensory effects
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 compositions exhibit significantly improved solubility and reduced subject-to-subject variability, enhancing the bioavailability and therapeutic potential of harmine for psychiatric, psychosomatic, and somatic disorders.
Implementation Method 1
compositions comprising harmine or its pharmaceutically acceptable salts in combination with uronic acids or carboxylic acids and monosaccharides are developed to enhance solubility
Data Source
AI summary
The present invention relates to a composition comprising harmine and (i) an uronic acid or (ii) a carboxylic acid and a monosaccharide, to a salt of harmine and uronic acid, to a kit of parts comprising (a) the composition or the salt of the invention and a pharmaceutically acceptable carrier and (b) DMT or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, to a pharmaceutical composition comprising the composition or the salt of the invention and a pharmaceutically acceptable carrier. The compositions, the salts, the kits of parts and the pharmaceutical compositions of the present invention are particularly useful in the treatment of psychiatric, psychosomatic or somatic disorders.