Dual Diffusion Layer Oral Preparation for Controlled Release

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Solution Overview

Problem

Conventional pharmaceutical preparations for oral administration with controlled release of active ingredients in the small intestine often result in a strong initial increase in active ingredient release, leading to high blood levels and increased side effects, along with inter-individual variation in plasma levels, especially when the entire daily dose is administered once.

Innovation Solution

A pharmaceutical preparation with active ingredient carriers featuring an inner layer composed of at least two diffusion layers, where the permeability for the active ingredient decreases from the inside out, combined with an enteric coating layer, to control the release and reduce initial peak plasma levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional pharmaceutical preparations with controlled release are used, then the active ingredient is released in the small intestine, but a strong initial increase in release occurs leading to high blood levels and increased side effects

Engineering Contradiction:
Improvecontrolled release in small intestineVSAvoidinitial peak plasma levels and side effects
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The inner layer is divided into at least two diffusion layers with different permeability characteristics. The first diffusion layer (innermost) has higher permeability while the second diffusion layer (outer) has lower permeability, creating a segmented release profile that prevents initial peak concentrations while maintaining controlled release throughout the intestinal transit time

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the inner layer are assigned different permeability properties. The inner diffusion layer allows faster diffusion to prevent initial peak, while the outer diffusion layer provides sustained release control, creating local quality variations that achieve both rapid initial release and sustained overall release

Inventive Principle:
Principle #3Local quality

2Adaptability or versatility

If enteric materials with different solubilities at different pH values are used, then release can be controlled depending on pH, but restrictions in material choice occur and uniform release is not achieved during pH fluctuations

Engineering Contradiction:
ImprovepH-dependent release controlVSAvoiduniform release during pH fluctuations
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

Instead of relying on pH-dependent solubility changes of enteric materials, the invention uses physical diffusion parameters (permeability coefficients) of the diffusion layers to control release. This parameter-based approach provides more reliable and uniform release control that is less sensitive to pH fluctuations while maintaining adaptability to different gastrointestinal conditions

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If the entire daily dose is administered once, then convenience is improved, but strong inter-individual variation in plasma level curves occurs

Engineering Contradiction:
Improvesingle daily administrationVSAvoidinter-individual variation in plasma levels
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The dual diffusion layer structure provides continuous and uniform release of the active ingredient throughout the entire intestinal transit time, ensuring that the useful pharmacological action is maintained continuously without sharp peaks or valleys, thereby reducing inter-individual variation while allowing single daily dosing

Inventive Principle:
Principle #20Continuity of useful action

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 design achieves a lower initial release rate of the active ingredient, resulting in sustained and uniform plasma concentrations, reducing side effects and inter-individual variation, allowing for effective daily dosing with a single administration.

Implementation Method 1

an inner layer for controlling the release of active ingredient, which is formed from at least two diffusion layers, the permeability of which for the diffusing active ingredient decreases

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

an enteric coating layer arranged thereon... which serves to ensure that the active ingredient passes through the patient's stomach unchanged and only dissolves when the active ingredient leaves the stomach and enters the small intestine

Methodology Applied
Scientific EffectpH-dependent dissolution:

Data Source

PatentEP1880718B1Pharmaceutical preparation for oral administration with controlled drug release in the small intestine colon and process of prepartion thereof
Publication Date: 2011.09.21 DR ROBERT PFLEGER CHEM FAB
  • EP1880718B1 patent drawingFigure 1
  • EP1880718B1 patent drawing

AI summary

Oral preparation (I) for controlled release of active ingredient in small intestine, comprises at least one active ingredient based on active ingredient carrier, where the active ingredient is provided with an internal layer for controlling the active ingredient release, and a covering layer that is resistant to gastric juice, where the inner layer is constructed with at least two diffusion layer, whose permeability for diffusing the active ingredient decreases from inside to outside, and the diffusion layer are formed from a matrix material insoluble in the small intestine juice. Oral preparation for controlled release of active ingredient in small intestine, comprises at least one active ingredient based on active ingredient carriers, where the active ingredient is provided with an internal layer for controlling the active ingredient release, and a covering layer that is resistant to gastric juice, where the inner layer is constructed with at least two diffusion layers, whose permeability for diffusing the active ingredient decreases from inside to outside, and the diffusion layer are formed from a matrix material insoluble in the small intestine juice, whose permeability for diffusing active ingredient is embedded with gastric juice soluble, swellable and/or water absorbing pore forming material. An independent claim is included for the preparation of (I) comprising coating active ingredient carrier with solution or suspension containing binder, releasing agent and optionally buffer substance, providing at least two diffusion layer, whose permeability for diffusing active ingredient decreases from inside to outside, and applying a gastric juice resistance coating layer, optionally with a saliva-resistant external layer. ACTIVITY : None given. MECHANISM OF ACTION : None given.