Naproxen Vitamin B6 Tablet Manufacturing via Segmented Granulation

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Solution Overview

Problem

Current treatments for low back pain, including naproxen and acetaminophen, often fail to adequately control pain in some patients, and there is a need for a more effective and compliant dosage form that combines naproxen with vitamin B complex to enhance pain management.

Innovation Solution

A solid oral dosage form is developed by extragranularly adding vitamin B6 to granules containing naproxen or its salt, which are then compressed into tablets or capsules, avoiding the challenges of capping and improving tablet hardness and friability, using a method that includes wet granulation with water as the processing solvent.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If naproxen is granulated with vitamin B6 using water as processing solvent for wet granulation, then manufacturing cost is reduced and sustainability is improved, but tablet hardness and friability requirements are not met

Engineering Contradiction:

Improvemanufacturing cost and sustainabilityVSAvoidtablet hardness and friability

Core Design Contradiction:

Ease of manufactureVSManufacturing precision

Solution Approach 1:

The manufacturing process is divided into two separate granulation steps: first granulating naproxen with its own binder system, then separately granulating vitamin B6 with its binder system. These two granulate systems are subsequently blended together. This segmentation allows each component to be optimized independently for its specific binding requirements, achieving both manufacturing efficiency and product quality specifications for hardness and friability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

A blend of naproxen granules and vitamin B6 granules serves as an intermediary system that combines two separately optimized granulate systems. Each granulate system uses water-soluble binders appropriate for its specific component, and their combination in a blended system allows both components to maintain their optimal physical properties while achieving the required tablet characteristics.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If naproxen sodium and vitamin B6 are granulated together, then a fixed-dose combination is achieved, but capping occurs during tablet compression

Engineering Contradiction:

Improvefixed-dose combinationVSAvoidcapping defect

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The granulation process is segmented into two independent operations: naproxen is granulated separately with water-soluble binders, and vitamin B6 is granulated separately with water-soluble binders. The resulting granulates are then blended to create the fixed-dose combination. This segmentation prevents the capping defect that occurs when the components are granulated together, while still achieving the therapeutic benefit of fixed-dose combination.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The granulation parameters are changed by using different binding conditions for each component. Naproxen granules are formed with specific water-soluble binders under controlled conditions, and vitamin B6 granules are formed with different water-soluble binders under optimized conditions. These parameter changes in the granulation process eliminate capping during subsequent tablet compression while maintaining fixed-dose combination integrity.

Inventive Principle:

Principle #35Parameter changes

3Device complexity

If naproxen is compressed into tablet without granulation, then manufacturing process is simplified, but compression is very difficult or impossible

Engineering Contradiction:

Improvemanufacturing process complexityVSAvoidcompressibility

Core Design Contradiction:

Device complexityVSEase of manufacture

Solution Approach 1:

Naproxen undergoes preliminary granulation with water-soluble binders before compression. This preliminary action transforms the raw naproxen powder into granules with improved flow and compression properties. The granulated naproxen can then be easily compressed into tablets, overcoming the compressibility difficulties of ungranulated naproxen while maintaining manufacturing process efficiency.

Inventive Principle:

Principle #10Preliminary action

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 fixed-dose combination of naproxen and vitamin B6 provides more effective pain relief for low back pain, improves patient compliance, and meets pharmaceutical industry quality standards, with reduced capping issues and enhanced manufacturing ease.

Implementation Method 1

granulating naproxen together with vitamin B6, using water as processing solvent for wet granulation

Methodology Applied

Scientific EffectWet granulation:

Implementation Method 2

granulating water-soluble naproxen sodium together with water-soluble vitamin B6, using water as processing solvent

Methodology Applied

Scientific EffectDissolution: Solvation

Data Source

PatentEP4021417B1Solid oral dosage form comprising naproxen and vitamin b6

Publication Date: 2023.10.04 DSM IP ASSETS BV

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AI summary

The present invention relates to a solid oral dosage form comprising naproxen and vitamin B6. Preferably, it is a solid oral dosage form for use in the treatment of pain such as low back pain. It is a fixed-dose combination (FDC) which increases patient compliance. The method of preparing such solid oral dosage form comprises the extragranular addition of vitamin B6 to an intragranular composition, wherein said intragranular composition comprises naproxen or a pharmaceutically acceptable salt thereof and at least one binder.