Sucralose-Based Effervescent NAC Formulation for Taste Masking

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Solution Overview

Problem

N-acetylcysteine-based pharmaceutical compositions, particularly in effervescent forms, face challenges in masking the unpleasant taste of degradation products, leading to high excipient requirements and stability issues, especially at high temperatures, making them difficult to prepare, store, and suitable for all patients.

Innovation Solution

An effervescent formulation using sucralose as a sweetener in combination with citric acid and sodium bicarbonate, reducing the total weight and excipient amount while maintaining a pleasant taste and stability, with specific weight ratios and amounts of N-acetylcysteine, citric acid, sodium bicarbonate, sucralose, and a flavoring agent.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If large amounts of sweeteners and flavouring agents are used to mask the unpleasant taste of NAC, then the taste masking effectiveness is improved, but the total weight of the composition increases and the complexity of preparation and storage worsens

Engineering Contradiction:
Improvetaste masking effectivenessVSAvoidtotal weight of composition
Core Design Contradiction:
Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent changes the chemical parameter of the sweetener from conventional options (aspartame, saccharin) to sucralose, which has superior taste masking properties. This parameter change allows effective taste masking with lower quantities, resolving the contradiction between taste masking effectiveness and total composition weight.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite formulation combining sucralose with specific flavouring agents (citric acid, sodium bicarbonate, and fruit flavours) to achieve synergistic taste masking effects. This composite approach improves taste masking while maintaining reduced excipient quantities compared to using单一 sweeteners.

Inventive Principle:
Principle #40Composite materials

2Ease of manufacture

If large amounts of excipients are used to achieve effective taste masking, then the taste masking is improved, but the difficulty of preparation, packaging and storage increases

Engineering Contradiction:
Improvetaste masking effectivenessVSAvoidpreparation and storage complexity
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

By changing the sweetener parameter to sucralose with higher potency and better stability characteristics, the formulation requires fewer excipients overall. This reduction in excipient quantity directly decreases the complexity of preparation, packaging, and storage operations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent adopts a formulation strategy that uses smaller quantities of excipients, simplifying the overall system. This reduces the material handling, packaging volume, and storage requirements, making the preparation and storage processes less complex.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Ease of manufacture

If conventional sweeteners are used in high dosage forms (600 mg NAC), then the unpleasant taste is partially masked, but the effectiveness is insufficient and requires excessive excipient amounts

Engineering Contradiction:
Improvetaste masking effectivenessVSAvoidamount of excipients
Core Design Contradiction:
Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent changes the sweetener parameter from conventional low-potency options to sucralose, which has approximately 600 times the sweetness of sucrose. This parameter change enables effective taste masking in high dosage forms (600 mg NAC) with minimal excipient quantities, resolving the contradiction between masking effectiveness and excipient amount.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a small but sufficient amount of sucralose (0.5-1% by weight) to achieve complete taste masking, rather than using large amounts of conventional sweeteners. This partial action approach is more efficient and reduces the overall excipient burden in the formulation.

Inventive Principle:
Principle #16Partial or excessive action

4Ease of manufacture

If NAC is formulated with high excipient content for taste masking, then the taste is improved, but the stability during storage especially at high temperatures worsens

Engineering Contradiction:
Improvetaste masking effectivenessVSAvoidstorage stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical composition parameter by selecting sucralose, which has superior thermal stability compared to conventional sweeteners. This parameter change maintains taste masking effectiveness while significantly improving storage stability, especially under high temperature conditions, thereby resolving the contradiction between taste improvement and stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

By using a stable, long-lasting sweetener like sucralose that maintains effectiveness throughout the product shelf life, the formulation avoids the degradation issues associated with less stable excipients. This ensures consistent taste masking and compositional stability during storage.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 achieves a pleasant taste and increased stability, reducing the total weight of N-acetylcysteine tablets to approximately 1.5g, improving palatability and storage stability, even at high temperatures, and allowing for cost-effective preparation and packaging.

Implementation Method 1

effervescent formulations comprising from 6 to 32% by weight of NAC, from 35 to 50% by weight of citric acid, from 26 to 37% by weight of sodium bicarbonate

Methodology Applied
Scientific EffectChemical reaction (acid-base): Chemical Bonding

Implementation Method 2

effervescent formulations of NAC comprising sucralose have a very pleasant taste that persists over time

Methodology Applied
Scientific EffectTaste masking:

Data Source

PatentEP2558065B1Effervescent pharmaceutical compositions containing n-acetylcysteine
Publication Date: 2016.06.08 ALPEX PHARMA SA

AI summary

An effervescent pharmaceutical composition containing N-acetylcysteine and sucralose is described.