SAMe Stabilization Using Calcium Oxide
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Solution Overview
Problem
S-adenosyl methionine (SAMe) is unstable at temperatures above 0°C and in the presence of moisture, leading to degradation and racemization, which complicates its use as a drug and dietary supplement, with existing stabilization methods being costly and inefficient, especially in solid oral formulations like tablets.
Innovation Solution
The use of calcium oxide to directly mix with SAMe or its salts, which reacts with water to permanently remove moisture, reducing the hygroscopic properties and stabilizing the active S,S diastereoisomer, thereby reducing racemization and increasing the stability of SAMe formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If S-adenosyl methionine is stored at temperatures above 0°C or in the presence of moisture, then it becomes more accessible for use, but it degrades and racemizes, converting active (SS)-(+)-SAMe to inactive (RS)-(+)-SAMe
Solution Approach 1:
Calcium oxide acts as an intermediary substance that absorbs moisture from the environment and from the SAMe formulation, preventing direct contact between water and SAMe. This mediator allows the SAMe to be stored at higher temperatures and in more accessible conditions while maintaining stability by intercepting the harmful moisture before it can cause degradation or racemization.
2Stability of the object's composition
If prior stabilization methods use high percentages (much higher than 50% by weight) of stabilizing substances like chitosan, dextrin, carboxymethylcellulose, fumaric acid, azelaic acid and tryptophan, then SAMe stability improves, but production costs increase and yields decrease due to low ion content in final product
Solution Approach 1:
The invention changes the parameter of stabilizing substance concentration from high percentages (much higher than 50% by weight) to a low percentage (less than 50% by weight, preferably less than 10%). Calcium oxide achieves superior stabilization at these reduced concentrations, thereby improving productivity by reducing production costs and increasing the ion content in the final product while maintaining or enhancing SAMe stability.
3Stability of the object's composition
If prior methods add stabilizing substances in reconstituted aqueous solution to S-adenosyl methionine salts followed by lyophilisation, then stability is achieved, but production costs increase and yields decrease
Solution Approach 1:
The invention extracts and eliminates the problematic aqueous solution step and lyophilisation process from the manufacturing method. By using calcium oxide to directly absorb moisture in a solid-state or concentrated solution form, the process removes the need for reconstitution in aqueous media and subsequent freezing-drying, thereby simplifying manufacturing, reducing costs, and improving yield while maintaining stability.
4Stability of the object's composition
If residual moisture content in SAMe powder after drying is reduced, then stability improves, but the complexity of drying processes increases
Solution Approach 1:
Calcium oxide provides self-service moisture control by automatically absorbing residual moisture from the SAMe powder after drying. This self-regulating mechanism eliminates the need for complex multi-stage drying processes or sophisticated moisture control equipment, as the calcium oxide continuously maintains low moisture levels through its hygroscopic properties, thereby reducing process complexity while enhancing stability.
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
This approach significantly reduces the moisture content in SAMe formulations to near zero, enhancing the stability and reducing racemization, resulting in more effective and stable SAMe products with improved pharmacological activity, particularly in tablets, while maintaining a synergistic antidepressant effect.
Implementation Method 1
calcium oxide to directly mix with SAMe or its salts, which reacts with water to permanently remove moisture
Implementation Method 2
reducing the hygroscopic properties and stabilizing the active S,S diastereoisomer
Data Source
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AI summary
This invention relates to solid oral compositions based on SAMe and/or NADH or their salts in association with calcium oxide and/or calcium hydroxide and a process for obtaining them. This invention also relates to a method for stabilising a solid oral composition based on SAMe and/or NADH or their salts, making use of calcium oxide, calcium hydroxide optionally in association with malic acid, glutamic acid, xylitol, calcium sulphate hemihydrate, magnesium oxide and/or mixtures thereof. This invention also relates to the use of SAMe or its salts in association with calcium oxide and/or calcium hydroxide with the possible further addition of melatonin and/or l-the^anine and/or 1 -tryptophan and/or 5- hydroxytryptophan for the treatment of depressive states.