Enteric Coated Pellets Stress Absorber Compression Integrity

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Solution Overview

Problem

Existing pharmaceutical formulations of benzimidazole derivatives, such as omeprazole and lansoprazole, face challenges with degradation in acidic stomach environments due to the brittleness of enteric coatings, which can lead to cracking during tablet compression, and the use of plasticizers in enteric coatings introduces solubility and stability issues.

Innovation Solution

A novel formulation featuring individually enteric-coated multiple units with an outer coating that acts as a stress absorber, devoid of plasticizers, to protect the integrity of the enteric coating during compression and enhance chemical stability, while allowing for rapid disintegration and improved flowability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If an enteric coating layer is applied to protect benzimidazole from acid degradation, then the chemical stability is improved, but the coating becomes brittle and cracks during tablet compression

Engineering Contradiction:
Improvechemical stabilityVSAvoidcoating integrity
Core Design Contradiction:
Stability of the object's compositionVSStrength

Solution Approach 1:

The patent divides the coating system into multiple functional layers: an enteric coating layer for chemical protection and an outer coating layer for mechanical protection. This segmentation allows each layer to specialize in one function, preventing the enteric layer from bearing compression stresses that would cause cracking.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a composite coating structure combining enteric polymers (for acid resistance) with outer coating materials containing stress absorbers like microcrystalline cellulose or starch. This composite approach integrates the benefits of both material types: chemical stability from the enteric layer and mechanical strength from the outer layer.

Inventive Principle:
Principle #40Composite materials

2Strength

If plasticizers are added to the enteric coating to reduce brittleness, then the coating flexibility is improved, but solubility and stability issues arise

Engineering Contradiction:
Improvecoating flexibilityVSAvoidsolubility stability
Core Design Contradiction:
StrengthVSStability of the object's composition

Solution Approach 1:

The patent removes plasticizers from the enteric coating formulation entirely, extracting the problematic component that caused solubility and stability issues. Instead, mechanical flexibility is achieved through the outer coating layer containing stress absorbers, eliminating the need for plasticizers in the enteric layer.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The outer coating layer acts as an intermediary between the enteric coating and the compression forces. It absorbs stresses and protects the enteric layer from mechanical degradation without requiring plasticizers, thereby maintaining both flexibility and chemical stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If multiple-unit enteric-coated pellets are compressed into tablets, then the dosage form is improved, but the enteric coating cracks under compression pressure

Engineering Contradiction:
Improvedosage formVSAvoidcoating resistance to compression
Core Design Contradiction:
Ease of operationVSStrength

Solution Approach 1:

The patent applies an outer coating layer beforehand to cushion the enteric coating against compression stresses. This outer layer contains stress absorbers that preemptively protect the enteric coating during the tablet compression process, preventing cracks before they occur.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

4Speed

If the enteric coating is made thinner to improve disintegration, then the disintegration speed is improved, but the protection against acid degradation is reduced

Engineering Contradiction:
Improvedisintegration speedVSAvoidacid protection
Core Design Contradiction:
SpeedVSStability of the object's composition

Solution Approach 1:

The patent segments the protection function from the disintegration function by creating separate layers: the enteric layer provides acid protection regardless of thickness, while the outer layer facilitates disintegration and rapid release in the intestinal tract, resolving the trade-off between protection and speed.

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 solution effectively prevents cracking of the enteric coating during compression, maintains chemical stability, and allows for rapid disintegration of the benzimidazole tablets, ensuring effective protection and absorption of the active ingredient without the drawbacks of plasticizer use.

Implementation Method 1

These polymers exhibit resistance to gastric fluids, yet are readily soluble or permeable in intestinal fluid. In the low pH of the stomach, the enteric polymers are unionized, and therefore, insoluble. As the pH increases in the intestinal tract, these functional groups ionize, and the polymer becomes soluble in the intestinal fluids.

Methodology Applied
Scientific EffectpH-dependent ionization:

Implementation Method 2

Each unit is entirely coated with an outer layer which protects the integrity of the enteric coating during compression. The outer coating comprises a stress absorber that prevents cracking under compression pressure.

Methodology Applied
Scientific EffectStress absorption: Stress Relaxation

Implementation Method 3

The small particles are mixed with the contents in gastrointestinal tract and are distributed over a large area. The enteric coating allows the coated solid to pass intact through the stomach to the small intestine, where the drug is then released for absorption.

Methodology Applied
Scientific EffectDisintegration:

Data Source

PatentEP2026768B1Multiple unit pharmaceutical formulation
Publication Date: 2018.02.28 DEXCEL PHARMA TECH LTD

AI summary

An orally disintegratable benzimidazole formulation, featuring a plurality of compressed pellets in a MUPS tablet. The individual units feature a substrate with the active ingredient and an enteric coating, optionally with a subcoating between the substrate and the enteric coating. The individual units are preferably at least partially coated with an outer coating which features a stress absorber, thereby enabling the pellets to be compressed without disturbing the integrity of the enteric coating. The enteric coating preferably does not feature a plasticizer.