Multilayer Tablet with Organic Acid for Magnesium Solubility

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Solution Overview

Problem

Magnesium deficiency disorders like fatigue and irritability are challenging to treat due to poor absorption of magnesium salts, particularly in solid oral forms like tablets, where pH changes in the gastrointestinal tract limit magnesium dissolution and absorption.

Innovation Solution

A multilayer tablet design with an immediate gastric release layer containing magnesium oxide or hydroxide, a disintegrating agent, and a binding polymer, combined with a sustained-release layer that forms a hydrogel matrix and includes an organic acid to maintain magnesium solubility, along with an optional inert layer to prevent interaction between release layers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If magnesium salts are administered in solid oral forms like tablets, then ease of operation is improved, but absorption is worsened due to pH changes in the gastrointestinal tract limiting magnesium dissolution

Engineering Contradiction:
Improveease of taking the supplementVSAvoidmagnesium absorption
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The tablet is divided into two distinct functional layers: an immediate-release layer containing magnesium salt and a sustained-release layer containing magnesium salt and organic acid. This segmentation allows each layer to perform its specific function - the immediate-release layer provides rapid magnesium absorption in the stomach, while the sustained-release layer maintains magnesium dissolution in the intestines despite pH changes.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

An organic acid is introduced as an intermediary substance in the sustained-release layer. This organic acid acts as a mediator that maintains an acidic microenvironment in the intestines, preventing precipitation of magnesium salts and enhancing their dissolution and absorption, thereby overcoming the pH-related absorption limitation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If magnesium salts are administered to achieve sufficient blood levels, then magnesium deficiency treatment is improved, but solubility is worsened at neutral and alkaline pH values

Engineering Contradiction:
Improvemagnesium blood level achievementVSAvoidmagnesium solubility
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent utilizes pH parameter changes to control magnesium solubility. By introducing organic acid in the sustained-release layer, the local pH is maintained at acidic levels where magnesium salts remain soluble. This parameter change (maintaining acidic pH) prevents precipitation and enhances magnesium dissolution in the intestinal tract.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The organic acid serves as a mediator that creates and maintains an acidic microenvironment in the intestines. This intermediary substance prevents the pH rise that would otherwise cause magnesium precipitation, thereby maintaining high solubility and enhancing magnesium absorption throughout the intestinal tract.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Duration of action of moving object

If sustained release of magnesium is achieved for several hours, then duration of action is improved, but dissolution is worsened due to gradually increasing pH in the intestinal tract

Engineering Contradiction:
Improveduration of magnesium releaseVSAvoidmagnesium dissolution
Core Design Contradiction:
Duration of action of moving objectVSQuantity of substance

Solution Approach 1:

The sustained-release layer is designed to continuously release magnesium throughout the intestinal tract. The organic acid in this layer continuously maintains an acidic microenvironment, ensuring continuous dissolution of magnesium salts despite the gradually increasing pH in the intestinal tract. This continuous action extends the duration of magnesium availability.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The organic acid acts as a continuous intermediary that maintains acidic conditions throughout the intestinal passage. This mediator prevents pH-induced precipitation of magnesium salts, ensuring sustained dissolution and release of magnesium over several hours as the tablet traverses the gastrointestinal tract.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 multilayer tablet design enhances magnesium absorption by ensuring immediate release in the stomach and sustained release in the intestinal tract, maintaining magnesium solubility through pH changes, thereby increasing blood magnesium levels effectively.

Implementation Method 1

a disintegrating agent... to accelerate release from the immediate gastric layer

Methodology Applied
Scientific EffectDisintegration:

Implementation Method 2

a polymer able to form a hydrogel matrix when it comes into contact with the fluids of the gastrointestinal tract

Methodology Applied
Scientific EffectHydrogel formation: Hydrogel

Implementation Method 3

an organic acid able to dissociate in the gastrointestinal fluids

Methodology Applied
Scientific EffectDissociation:

Implementation Method 4

maintaining magnesium solubility through pH changes

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 5

The multilayer tablet design with an immediate gastric release layer containing magnesium oxide or hydroxide, a disintegrating agent, and a binding polymer, combined with a sustained-release layer

Methodology Applied
Scientific EffectLayered structure separation:

Data Source

PatentEP3357492B1Multilayer tablet for administration of magnesium
Publication Date: 2019.12.04 S I I T SRL

AI summary

Disclosed is a multilayer tablet for controlled release of magnesium, which takes place by means of immediate release into the stomach and sustained release into the intestinal tract. The tablet is used to treat magnesium deficiency.