Enteric-Coated Tablet for P-CAB and Aspirin Stability

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Solution Overview

Problem

Developing a tablet formulation that effectively combines potassium-competitive acid blockers (P-CAB) like vonoprazan with acetylsalicylic acid, which poses challenges in stability and pharmacological efficacy due to the complexity of optimizing the dissolution rates of multiple active ingredients and managing adverse interactions.

Innovation Solution

An enteric-coated tablet design with acetylsalicylic acid as the inner core and vonoprazan in an outer layer, free of enteric coating, where the content ratio of vonoprazan to fumaric acid is optimized to enhance stability and rapid pharmacological effect.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If acetylsalicylic acid is administered to suppress thrombus and/or embolization, then antiplatelet therapy is achieved, but gastric ulcer or duodenal ulcer is induced

Engineering Contradiction:
Improveantiplatelet therapy efficacyVSAvoidgastric ulcer or duodenal ulcer
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an enteric coating layer as an intermediary substance between acetylsalicylic acid and the gastric mucosa. This coating layer protects the stomach from direct contact with the drug, preventing ulcer formation while maintaining the antiplatelet effect. The enteric coating dissolves in the alkaline environment of the intestine, allowing drug absorption away from the vulnerable gastric tissue.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The tablet is segmented into distinct functional layers: an enteric-coated core containing acetylsalicylic acid and an outer layer containing vonoprazan. This segmentation allows the acetylsalicylic acid to be protected from gastric acid until it reaches the intestine, while vonoprazan provides immediate gastric acid suppression to prevent ulcer formation.

Inventive Principle:
Principle #1Segmentation

2Object-affected harmful factors

If proton pump inhibitors are used to suppress gastric acid secretion, then gastric mucosal protection is achieved, but instability under acidic conditions and variations in effects based on metabolic enzyme polymorphisms occur

Engineering Contradiction:
Improvegastric mucosal protectionVSAvoidinstability under acidic conditions
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent switches from using traditional proton pump inhibitors (which are unstable in acidic conditions) to vonoprazan, a potassium-competitive acid blocker that maintains stable activity across a wide pH range (1.2-7.4). This parameter change in drug selection eliminates the instability problem while maintaining effective gastric acid suppression and mucosal protection.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If multiple active ingredients are combined in a tablet, then dissolution rate optimization is required, but formulation complexity increases

Engineering Contradiction:
Improvedissolution rate optimizationVSAvoidformulation complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The tablet is divided into functionally distinct layers: an enteric-coated core containing acetylsalicylic acid and an outer layer containing vonoprazan. This segmentation allows each ingredient to dissolve at the appropriate location and time - vonoprazan dissolves immediately in the stomach to suppress acid, while the enteric-coated acetylsalicylic acid dissolves in the intestine to prevent ulceration. This simplifies formulation compared to attempting to control dissolution of multiple ingredients in a single homogeneous matrix.

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 tablet achieves stable and rapid expression of pharmacological effects, maintaining the convenience of administration while ensuring the preservation and dissolution stability of both active ingredients, effectively treating gastric ulcers and suppressing their onset.

Implementation Method 1

the inner core is an enteric-coated tablet comprising acetylsalicylic acid

Methodology Applied
Scientific EffectEnteric coating: Coatings

Implementation Method 2

the content ratio of the P-CAB and the fumaric acid (P-CAB:fumaric acid) is 1:0.001 to 1:0.01 in a weight ratio

Methodology Applied
Scientific EffectpH buffering:

Data Source

PatentEP3329921B1tablet
Publication Date: 2024.03.27 TAKEDA PHARMA CO LTD

AI summary

The present invention provides a tablet showing high stability of the active ingredients (potassium-competitive acid blocker and acetylsalicylic acid) and stably and rapidly expressing the pharmacological effects of the active ingredients after administration. The present invention provides a tablet containing an inner core and an outer layer, wherein the inner core is an enteric-coated tablet containing acetylsalicylic acid, and the outer layer contains a potassium-competitive acid blocker free of enteric coating.