Multilayer pH-Dependent Coating for Controlled Bicarbonate Release

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current pharmaceutical compositions fail to effectively release bicarbonate in the acidic environment of the stomach and duodenum, leading to uncontrolled and early release of active agents, which is not suitable for treating acid-base balance disturbances in the upper part of the small intestine.

Innovation Solution

A pH-dependent gradual sustained release pharmaceutical composition with a multilayer polymer coating, comprising cationic and anionic polymer layers, is developed to resist acidic pH and release bicarbonate in a controlled manner at pH 4.5 to 5.5, ensuring gradual and sustained release in the duodenum.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a simple polymer coating is used to protect bicarbonate in the stomach, then the coating must be resistant to acidic pH, but this prevents controlled release in the duodenum where pH is only slightly acidic

Engineering Contradiction:
Improvecoating resistance to gastric acidVSAvoidcontrolled release capability at different pH levels
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The coating is divided into multiple functional layers: an inner enteric coating resistant to gastric acid that dissolves at duodenal pH, and an outer pH-dependent coating that dissolves at higher pH. This segmentation allows each layer to perform its specific function - protecting bicarbonate in the stomach while enabling controlled release in the duodenum

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses a composite coating structure combining different polymer materials with distinct pH-dependent properties. The inner layer uses enteric polymers that dissolve at pH 5-6, while the outer layer uses pH-dependent polymers that dissolve at pH 6.5-7.5, creating a composite system that provides both gastric protection and controlled duodenal release

Inventive Principle:
Principle #40Composite materials

2Reliability

If bicarbonate is released early in the stomach, then the coating resistance is compromised, but this causes uncontrolled release and gas formation that worsens gastric distension

Engineering Contradiction:
Improvemaintaining coating integrityVSAvoidgastric distension from uncontrolled gas formation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The enteric coating is designed to preemptively prevent bicarbonate release in the gastric environment by maintaining coating integrity at low pH. This preliminary protective action prevents the harmful reaction between bicarbonate and gastric acid that would cause uncontrolled gas formation and gastric distension

Inventive Principle:
Principle #9Preliminary anti-action

Solution Approach 2:

The pH-dependent outer coating layer acts as an intermediary that controls the timing and location of bicarbonate release. It prevents direct contact between the inner enteric coating and the gastric environment, allowing the system to maintain coating integrity while preparing for controlled release in the duodenum

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If the coating dissolves at low pH to release bicarbonate early, then bicarbonate availability increases, but this prevents targeted delivery to the duodenum where it is needed

Engineering Contradiction:
Improvebicarbonate availabilityVSAvoidtargeted delivery to duodenum
Core Design Contradiction:
Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The coating system provides different dissolution properties at different locations: the inner enteric coating dissolves specifically at duodenal pH (5-6) while remaining intact in the stomach, and the outer pH-dependent coating dissolves at higher pH in the jejunum. This local quality differentiation ensures bicarbonate is released exactly where needed in the upper small intestine

Inventive Principle:
Principle #3Local quality

4Manufacturing precision

If a multilayer pH-dependent coating system is used to achieve controlled release, then release precision is improved, but the device complexity increases

Engineering Contradiction:
ImprovepH-dependent release precisionVSAvoidmultilayer coating structure
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The complex release profile is achieved by segmenting the coating into distinct functional layers, each with a specific pH dissolution threshold. This segmentation simplifies the manufacturing process compared to creating a single complex coating, as each layer can be applied and optimized independently to achieve the desired multi-stage release pattern

Inventive Principle:
Principle #1Segmentation

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 effectively increases the pH in the duodenum, alleviating acid load and preventing digestive disorders by providing bicarbonate directly to the duodenum, thus addressing bicarbonate deficiencies and promoting optimal digestion and absorption.

Implementation Method 1

the coating of the first type of microparticles is resistant to acidic pH below a well defined first pH threshold value but disrupts above this pH threshold value

Methodology Applied
Scientific EffectpH-dependent solubility:

Implementation Method 2

bicarbonate can be used orally for the neutralization of the gastric acid

Methodology Applied
Scientific EffectAcid-base neutralization:

Data Source

PatentEP2598116B1PH-dependent gradual release pharmaceutical composition
Publication Date: 2018.06.20 HAJNAL PETER
  • EP2598116B1 patent drawingFigure 1
  • EP2598116B1 patent drawingFigure 2a
  • EP2598116B1 patent drawingFigure 2b

AI summary

The invention concerns a pH-dependent gradual sustained release composition for increasing the pH in the upper part of the small intestines. Particles of the composition are provided with a multilayer polymer coating of specific structure which ensures the gradual release of the active agent in the range of pH 4.5 to 5.5. A process for preparing said composition is also claimed.