Orodispersible Tablets Bitter Taste Masking

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Solution Overview

Problem

Current methods for masking the unpleasant taste of pharmacologically active substances, such as fluoxetine, which are bitter and cause a burning sensation, are insufficient and require excessive polymer coating, compromising dissolution kinetics in acid media.

Innovation Solution

Complexing the active principle with a weak cation-exchange resin and incorporating a hydrophilic adsorbent during granulation, followed by coating with a gastrosoluble polymer, to effectively mask taste and ensure rapid release in an acid medium.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If coating with gastrosoluble polymer is used to mask the unpleasant taste of bitter active principles, then the taste masking is improved, but the dissolution kinetics in acid medium deteriorates due to excessive polymer amounts required

Engineering Contradiction:
Improvebitter taste and burning sensationVSAvoiddissolution rate in acid medium
Core Design Contradiction:
Object-affected harmful factorsVSSpeed

Solution Approach 1:

The coating system is segmented into multiple functional layers: an inner layer containing the active principle complexed with cation-exchange resin for taste masking, and an outer gastrosoluble polymer coating for protection. This segmentation allows the inner layer to dissolve rapidly in acid medium while the outer layer provides taste masking, resolving the contradiction between taste masking and dissolution rate.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The formulation uses a composite structure combining the active principle with cation-exchange resin in the inner layer, surrounded by a gastrosoluble polymer outer layer. This composite material approach enables simultaneous achievement of rapid dissolution (through the soluble inner layer) and effective taste masking (through the polymer coating), overcoming the limitation of using excessive polymer alone.

Inventive Principle:
Principle #40Composite materials

2Ease of manufacture

If simple complexing with cation-exchange resin is used to mask the taste of particularly bitter substances, then the manufacturing process is simplified, but the taste masking is insufficient for substances like fluoxetine

Engineering Contradiction:
Improvemanufacturing process simplicityVSAvoidbitter taste and burning sensation
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The formulation combines the active principle with cation-exchange resin in a composite inner layer that maintains manufacturing simplicity while significantly enhancing taste masking effectiveness. This composite structure provides better taste masking than simple complexing alone, particularly for substances like fluoxetine, without complicating the manufacturing process.

Inventive Principle:
Principle #40Composite materials

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 approach effectively masks the bitter taste and burning sensation while achieving rapid dissolution kinetics that meet the specifications of the USP monograph for fluoxetine tablets, with a dissolution rate greater than 85% in 15 minutes in a 0.1 N HCl solution.

Implementation Method 1

complexing, in a known manner, the active principle with a weak cation-exchange resin comprising carboxylic acid groups

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

carrying out the granulation of the complex thus obtained in the presence of at least 15 wt %, relative to the resin/active principle complex, of at least one hydrophilic adsorbent

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 3

subjecting the granules thus obtained to coating with a gastrosoluble polymer

Methodology Applied
Scientific EffectCoating: Coatings

Data Source

PatentUS8865219B2Orodispersible tablets of bitter active principles
Publication Date: 2014.10.21 ETHYPHARM SA

AI summary

The invention concerns coated granules including (A) at least one amine-containing pharmacological active principle, preferably as an acid addition salt, the pharmacological active principle being complexed by low cation-exchange resin containing carboxylic acid groups (COO″), and (B) at least 15 wt. %, based on the total weight of the active principle/low cation-exchange resin complex, of at least one hydrophilic adsorbent, the mixture of the components (A) and (B) being coated with a gastrosoluble polymer. The invention also concerns a method for preparing such granules, as well as orodispesible tablets containing such granules.