Odorless N-Acetylcysteine Tablets via Dry Granulation

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Solution Overview

Problem

High-dose NAC tablets with a sulfurous odor are unpleasant for patients, leading to difficulties in administration due to the need for high quantities of excipients to mask the odor, resulting in large and unpleasant tablets, and existing solutions do not completely eliminate the odor during storage.

Innovation Solution

A dry granulation process is used to prepare a granulate of NAC without aqueous solutions, eliminating the need for external film coating and reducing production steps, allowing for high-dose, odorless tablets with a high NAC content by mixing the granulate with pharmaceutically acceptable excipients and compressing them.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If high-dose NAC tablets are formulated with high quantities of excipients to mask the sulfurous odor, then the odor is reduced, but the tablet size increases making them difficult and unpleasant to swallow

Engineering Contradiction:
Improvesulfurous odorVSAvoidtablet size
Core Design Contradiction:
Object-affected harmful factorsVSVolume of moving object

Solution Approach 1:

The patent extracts and removes the source of the sulfurous odor (NAC degradation products) through optimized manufacturing processes and protective coating formulations, eliminating the need for large quantities of masking excipients while maintaining acceptable odor levels

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies film coating technology to create a protective barrier around the NAC core, preventing odor release without requiring excessive excipients. The coating film provides odor containment while maintaining compact tablet dimensions for easy swallowing

Inventive Principle:
Principle #30Flexible shells and thin films

2Ease of manufacture

If wet granulation process with aqueous solutions is used to prepare NAC tablets, then the granulate can be formed, but the sulfurous odor increases during storage

Engineering Contradiction:
Improvegranulate formationVSAvoidsulfurous odor during storage
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent changes the granulation approach by using dry or reduced-moisture processes instead of traditional wet granulation with aqueous solutions. This parameter change prevents the conditions that promote NAC degradation and odor formation during storage, while still achieving adequate granulate formation for tablet manufacturing

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a protective environment during manufacturing and storage that minimizes exposure to conditions promoting degradation. This includes controlling humidity and using protective coatings that create an inert barrier around the NAC, preventing odor development during storage

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

3Object-affected harmful factors

If external film coating is applied to mask the sulfurous odor, then the odor is reduced, but the production steps and complexity increase

Engineering Contradiction:
Improvesulfurous odorVSAvoidproduction process complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent combines multiple functions into integrated process steps. The granulation and coating processes are optimized to work together in a streamlined sequence, reducing the number of separate production steps while maintaining effective odor control. Excipients serve multiple purposes including odor masking, tablet formation, and coating integration

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP3003278B1Swallowable n-acetylcysteine tablets
Publication Date: 2019.02.27 ZAMBON SPA
  • EP3003278B1 patent drawingFigure 1~2

AI summary

This invention relates to swallowable tablets containing at least 80% by weight of N-acetylcysteine (NAC) and at least one pharmaceutically acceptable excipient, in particular tablets in which the sulfurous odor is absent, characterized in that the said tablets are assembled using a granulate prepared by means of a process of dry granulating the active ingredient alone, with which the excipients are mixed before compression.