Melatonin Controlled-Release Formulation with Acidified Polymeric Matrix

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Solution Overview

Problem

Melatonin administered orally has low bioavailability and rapid elimination due to its solubility issues in varying gastrointestinal pH environments, leading to variable and ineffective release profiles for treating sleep disorders and other conditions.

Innovation Solution

A controlled-release pharmaceutical dosage form combining melatonin with GABA receptor agonists or analgesic ingredients, such as valerian and salicin, within acidified polymeric matrices that release these compounds over 2-10 hours, maintaining therapeutic levels and reducing middle-of-the-night awakenings and morning grogginess.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If immediate release formulation is used, then rapid onset of action is achieved, but duration of action is too short leading to middle of the night awakening

Engineering Contradiction:

Improveonset of actionVSAvoidduration of melatonin effect

Core Design Contradiction:

SpeedVSDuration of action of moving object

Solution Approach 1:

The dosage form is divided into multiple compartments or layers, each containing melatonin that releases at different rates. This segmentation allows the first compartment to provide rapid onset while subsequent compartments provide sustained release, resolving the contradiction between fast onset and long duration.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses polymers with different degradation rates or solubility characteristics to create zones with varying release parameters. By changing the physical-chemical parameters of the matrix materials, the formulation achieves both rapid initial release and prolonged sustained release phases.

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If controlled release over 3-10 hours is implemented, then duration of action is extended, but variable response in patients persists with poor bioavailability

Engineering Contradiction:

Improverelease periodVSAvoidresponse consistency

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The patent introduces specific polymer matrices as intermediaries that control and standardize the release of melatonin. These polymers act as mediators between the drug and the gastrointestinal environment, providing consistent release profiles that overcome variable patient responses and poor bioavailability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The formulation uses composite materials combining melatonin with specific polymers and excipients that enhance solubility and control release. This composite approach improves bioavailability while maintaining reliable consistent response across different patients.

Inventive Principle:

Principle #40Composite materials

3Ease of operation

If melatonin is administered orally, then ease of administration is improved, but bioavailability is low due to solubility issues in varying pH environments

Engineering Contradiction:

Improveadministration convenienceVSAvoidbioavailability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent modifies the pH environment within the dosage form by incorporating buffering agents or pH-modifying excipients. This parameter change ensures that melatonin remains in a soluble form throughout the gastrointestinal tract despite varying pH conditions, thereby improving oral bioavailability while maintaining ease of administration.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses solubility-enhancing excipients and polymer matrices as intermediaries that protect melatonin from pH-related precipitation. These intermediaries maintain drug solubility through the gastrointestinal tract, ensuring reliable absorption while keeping the oral route convenient.

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 controlled-release formulation provides sustained melatonin and sedative or analgesic effects, enhancing sleep quality and pain relief by maintaining therapeutic levels throughout the night, regardless of gastrointestinal pH variations.

Implementation Method 1

acidified polymeric matrices that release these compounds over 2-10 hours, maintaining therapeutic levels and reducing middle-of-the-night awakenings and morning grogginess

Methodology Applied

Scientific EffectpH buffering:

Data Source

PatentUS10888522B2Controlled-release compositions of melatonin combined with sedative and/or analgesic ingredients

Publication Date: 2021.01.12 SOCIETE DES PRODUITS NESTLE SA

AI summary

Controlled-release therapeutic compositions including melatonin combined with sedative and/or analgesic ingredients are described. The compositions have a solid core including melatonin in an acidified polymeric matrix. A sedative ingredient such as GABA receptor agonist may also be in the acidified polymeric matrix. The composition may include an expedited release portion providing a burst release of active ingredients and a sustained release portion providing a sustained release of active ingredients.