Cetirizine-Polyol Complex for Stable Taste-Masking

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Solution Overview

Problem

Cetirizine is prone to degradation by esterification when combined with polyols in tablets, leading to an initial bitter taste due to its susceptibility in dry environments, which existing methods fail to effectively address for taste-masking purposes.

Innovation Solution

A wet formulation process involving cetirizine, a polyol, and an alkalizing agent at a pH of 2.5 to 4 is used to form a cetirizine-polyol complex, which is then isolated and formed into a tablet, allowing for higher molar equivalents of polyol and minimizing esterification, thereby stabilizing cetirizine and enabling effective taste-masking.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cetirizine and polyols are combined in a dry environment to prevent esterification, then degradation is reduced, but taste-masking effectiveness is compromised due to initial bitterness

Engineering Contradiction:
Improvestability of cetirizineVSAvoidbitter taste
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the environmental parameters from dry to wet conditions during manufacturing, and adjusts pH to alkaline levels (above 7) to enable stable coexistence of cetirizine and polyols without esterification, while allowing taste-masking to occur

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary complexation of cetirizine with polyols under controlled wet and alkaline conditions before tablet formation, ensuring the taste-masking effect is already in place before the tablet is consumed, eliminating initial bitterness

Inventive Principle:
Principle #10Preliminary action

2Reliability

If cetirizine and polyols are physically separated to prevent esterification, then degradation is reduced, but manufacturing complexity increases

Engineering Contradiction:
Improvestability of cetirizineVSAvoidmanufacturing process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges the separation requirement with the manufacturing process by incorporating both cetirizine and polyols into a single wet formulation under alkaline conditions, eliminating the need for separate storage or handling of components while preventing esterification through pH control

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent uses alkaline pH as an intermediary condition that mediates between cetirizine and polyols, allowing them to coexist stably without direct harmful interaction, thus simplifying the manufacturing process while maintaining stability

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If higher levels of polyols are used for taste-masking, then bitterness is reduced, but esterification degradation increases

Engineering Contradiction:
Improvebitter tasteVSAvoidstability of cetirizine
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent changes the pH parameter to alkaline conditions, which fundamentally alters the chemical behavior between polyols and cetirizine, allowing high levels of polyols to be used for effective taste-masking without triggering esterification degradation

Inventive Principle:
Principle #35Parameter changes

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 method allows for the stable combination of cetirizine and polyols in tablets, reducing degradation and bitterness, enabling effective taste-masking and maintaining the stability of cetirizine during storage, with less than 0.5% ester and oxidative degradation after 3 months at accelerated conditions.

Implementation Method 1

the solvent contains water and an alkalizing agent and has a pH from 2.5 to 4

Methodology Applied
Scientific EffectpH adjustment:

Implementation Method 2

mixing cetirizine, a polyol, and a solvent for the cetirizine to form a cetirizine:polyol complex

Methodology Applied
Scientific EffectComplexation:

Data Source

PatentEP2344137B1Method for making cetirizine tablets
Publication Date: 2015.12.02 JOHNSON & JOHNSON CONSUMER INC

AI summary

In one aspect, the present invention features a method of producing a tablet including cetirizine including the steps of: (i) mixing cetirizine, a polyol, and a solvent for the cetirizine to form a cetirizine:polyol complex, wherein the solvent comprises water and an alkalizing agent and has a pH from about 2 to about 7; (ii) isolating particles of the cetirizine:polyol complex from the mixture; and (iii) forming the particles into a tablet.