Esomeprazole Sodium Bicarbonate Tablet Stability via PVA Coating

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Omeprazole, especially its enantiomer esomeprazole, is prone to degradation in acidic and neutral media, and its compatibility with sodium bicarbonate leads to the production of impurities, while existing formulations using sodium bicarbonate can cause side effects and instability due to excessive sodium intake.

Innovation Solution

A pharmaceutical formulation comprising omeprazole or its enantiomer with sodium bicarbonate, where polyvinyl alcohol is used as a coating agent to prevent direct contact between omeprazole and sodium bicarbonate, enhancing stability and bioavailability by forming a multi-layered tablet with polyvinyl alcohol in both inner and outer layers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If sodium bicarbonate is used to stabilize omeprazole, then stability is improved, but compatibility deteriorates due to impurity production

Engineering Contradiction:

ImprovestabilityVSAvoidimpurity production

Core Design Contradiction:

Stability of the object's compositionVSObject-generated harmful factors

Solution Approach 1:

The formulation is divided into distinct granule types: acid-resistant granules containing omeprazole and alkaline granules containing sodium bicarbonate. This segmentation prevents direct contact between the two components during storage and transport, eliminating impurity production while maintaining stability when needed.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces acid-resistant coating materials as intermediaries that wrap the omeprazole granules, creating a protective barrier that prevents direct interaction between omeprazole and sodium bicarbonate. This intermediary layer allows both components to coexist without compatibility issues.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Stability of the object's composition

If enteric coating is used to improve stability, then stability is improved, but ease of operation deteriorates due to delayed absorption

Engineering Contradiction:

ImprovestabilityVSAvoidabsorption speed

Core Design Contradiction:

Stability of the object's compositionVSEase of operation

Solution Approach 1:

Different regions of the formulation have different properties: acid-resistant granules provide stability in the stomach, while alkaline granules provide buffering capacity. The acid-resistant coating is applied locally only where needed to protect omeprazole, allowing immediate absorption without delayed-release enteric coating.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

Instead of using enteric coating to protect omeprazole from acid (which delays absorption), the patent inverts the approach by using acid-resistant granules and alkaline granules in separate compartments. This allows immediate absorption while maintaining stability through the acid-resistant properties of the coating and the buffering capacity of sodium bicarbonate.

Inventive Principle:

Principle #13The other way round (Inversion)

3Stability of the object's composition

If large amount of sodium bicarbonate is used to stabilize omeprazole, then stability is improved, but harmful factors increase due to side effects

Engineering Contradiction:

ImprovestabilityVSAvoidside effects

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent uses a balanced amount of sodium bicarbonate that is sufficient to provide buffering capacity and stabilize omeprazole when needed, but not excessive to cause harmful side effects. The acid-resistant granule structure ensures that sodium bicarbonate is released only when needed, optimizing the balance between stability and safety.

Inventive Principle:

Principle #16Partial or excessive 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

The formulation significantly improves the stability and bioavailability of omeprazole, reducing impurity production and allowing immediate absorption in the stomach, while minimizing side effects associated with sodium bicarbonate use.

Implementation Method 1

The formulation as prepared based on the method described above is currently being marketed under the trade name of Nexium®. However, an enteric-coated tablet such as Nexium® is not suitable for the treatment of diseases requiring immediate therapeutic effect after administration

Methodology Applied

Scientific EffectPhysical containment: Physical Containment

Implementation Method 2

Korean Patent No. 679767 discloses a method of using a buffering agent such as sodium bicarbonate for omeprazole

Methodology Applied

Scientific EffectBuffering:

Implementation Method 3

decomposition of esomeprazole is catalyzed by an acidic compound, and also affected by moisture, heat, organic solvents, and light

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentUS11759428B2Pharmaceutical formulation comprising esomeprazole and sodium bicarbonate

Publication Date: 2023.09.19 CHONG KUN DANG PHARMACEUTICAL CORP

AI summary

The present invention relates to a stable pharmaceutical formulation comprising omeprazole, its enantiomer, or its pharmaceutically acceptable salt, and sodium bicarbonate, and a method for preparing the same. Specifically, the present invention provides a stable formulation by preventing omeprazole, its enantiomer, or its pharmaceutically acceptable salt, from coming in direct contact with sodium bicarbonate, to reduce the production of impurities.