Cross-linked High Amylose Starch Sustained Release Matrix

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Solution Overview

Problem

Current drug delivery systems often result in rapid drug release, leading to short therapeutic windows and uncontrolled adverse events, necessitating multiple doses and precise dosing regimens, which are challenging to manage, especially when the dosage form is broken or subdivided.

Innovation Solution

A solid, sustained release pharmaceutical composition comprising a cross-linked high amylose starch matrix with a solvent accessible surface, allowing for precise control of drug release kinetics, maintaining effective plasma concentrations for up to 24 hours and enabling the composition to be subdivided into smaller units with similar release profiles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If a polymer coating is applied to control drug release, then sustained release is achieved, but the coating may be broken or damaged during administration resulting in rapid drug release

Engineering Contradiction:
Improvesustained release durationVSAvoidcoating integrity
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The patent changes the physical-chemical parameters of the matrix material by using cross-linked high amylose starch instead of conventional polymer coatings. This cross-linked structure provides both sustained release capability and mechanical integrity, resolving the contradiction between sustained release duration and coating reliability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite matrix system combining cross-linked high amylose starch with pharmaceutical excipients. This composite structure integrates the sustained release properties of the starch matrix with the mechanical strength needed to prevent breaking during administration, simultaneously achieving both sustained release and reliability.

Inventive Principle:
Principle #40Composite materials

2Duration of action of moving object

If multiple sequential doses are administered to maintain therapeutic efficacy, then sustained therapeutic effect is achieved, but the dosing regimen becomes complex and difficult to manage

Engineering Contradiction:
Improvetherapeutic efficacy durationVSAvoiddosing regimen complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent segments the dosing strategy by creating a single sustained release formulation that inherently divides the dosing interval. The matrix structure is designed to release drug progressively over extended periods, allowing patients to take one dose instead of multiple sequential doses, thereby reducing dosing regimen complexity while maintaining therapeutic efficacy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent ensures continuous therapeutic action through the cross-linked starch matrix that provides sustained drug release over extended periods. This continuous release mechanism eliminates the need for multiple discrete doses, maintaining therapeutic efficacy while simplifying the dosing regimen to a single administration.

Inventive Principle:
Principle #20Continuity of useful action

3Adaptability or versatility

If the dosage form is broken or subdivided, then dosing flexibility is improved, but the release profile changes resulting in rapid drug release

Engineering Contradiction:
Improvedosing flexibilityVSAvoidrelease profile control
Core Design Contradiction:
Adaptability or versatilityVSDuration of action of moving object

Solution Approach 1:

The patent modifies the matrix structure parameters by using cross-linked high amylose starch, which maintains its structural integrity and release characteristics even when the dosage form is broken or subdivided. This parameter change ensures that subunits retain the sustained release profile, allowing dosing flexibility without compromising release control.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Instead of the conventional approach where breaking the dosage form destroys the release control mechanism, the patent inverts this expectation by designing a matrix that maintains release control integrity even after breaking. The cross-linked starch structure ensures that subunits produced by breaking the tablet still exhibit sustained release characteristics, thereby preserving release profile control while enabling dosing flexibility.

Inventive Principle:
Principle #13The other way round (Inversion)

4Measurement precision

If a single tablet is used for precise dosing, then dosing precision is improved, but the tablet must be sub-divided which may compromise release control

Engineering Contradiction:
Improvedosage precisionVSAvoidrelease control
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent changes the matrix material parameters to cross-linked high amylose starch, which maintains release control reliability even when the tablet is sub-divided for precise dosing. This parameter change allows the tablet to be safely divided into smaller units while preserving the sustained release characteristics, thereby achieving both dosing precision and release control reliability.

Inventive Principle:
Principle #35Parameter changes

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 composition achieves stable and controlled drug release, maintaining therapeutic efficacy for extended periods, allowing for precise dosing adjustments and minimizing adverse events by ensuring that subdivided units have the same release kinetics as the intact form, thus providing flexible and accurate drug delivery.

Implementation Method 1

The release rate of the therapeutic agent can then be altered by factors including the thickness of the coating, the diffusivity of agent through the coating

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

the rate of biodegradation of the coating

Methodology Applied
Scientific EffectBiodegradation: Decomposition (biological)

Implementation Method 3

the matrix comprises cross-linked high amylose starch

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Data Source

PatentEP1940467B1Sustained drug release composition
Publication Date: 2016.11.02 PALADIN LABS INC
  • EP1940467B1 patent drawingFigure 1
  • EP1940467B1 patent drawingFigure 2~3
  • EP1940467B1 patent drawingFigure 4~5

AI summary

The invention relates to a sustained release formulation for delivering one or more pharmaceutically active agents The formulation comprises cross-linked high amylose starch and at least one pharmaceutically active agent, and, when subdivided into smaller dosage forms, the smaller dosage forms have substantially the same sustained release properties as the formulation from which they were derived The formulations can provide sustained release for up to at least 24 hours, and because of their divisability permits a recipient of the active agent or the person administering the active agent to titrate the dosage of the agent.