Low Viscosity Cellulose Ether Liquid Composition Stability

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Solution Overview

Problem

Existing liquid compositions comprising an organic liquid diluent and a cellulose ether are not storage stable, leading to a significant viscosity increase over time, which limits the achievable concentration of cellulose ether and increases storage and transportation costs.

Innovation Solution

Incorporating a non-ionic cellulose ether with a viscosity of up to 2.33 mPa·s into the liquid composition, which is more stable and maintains flowability, allowing for higher cellulose ether concentrations and reduced viscosity increase during storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a cellulose ether is incorporated into the liquid composition, then the solubility and bioavailability of poorly water-soluble drugs is improved, but the viscosity of the liquid composition increases significantly over storage time

Engineering Contradiction:
Improvesolubility and bioavailability of drugVSAvoidviscosity stability during storage
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by selecting cellulose ethers with specific viscosity ranges (10-100 cP at 2% concentration) and controlling their concentration in the liquid composition (5-50% w/w). By optimizing these parameters, the formulation achieves sufficient drug solubility enhancement while maintaining acceptable viscosity stability during storage at room temperature.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by combining cellulose ethers with specific organic liquid diluents (such as glycerol, propylene glycol, or polyethylene glycol) to create a synergistic liquid composition. This composite system leverages the solubility-enhancing properties of cellulose ether while the organic diluent provides flowability and storage stability, preventing excessive viscosity increase over time.

Inventive Principle:
Principle #40Composite materials

2Reliability

If the concentration of cellulose ether in the liquid composition is increased, then the drug solubility and bioavailability is enhanced, but the storage and transportation costs increase due to higher viscosity

Engineering Contradiction:
Improvedrug solubility and bioavailabilityVSAvoidstorage and transportation costs
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent optimizes the concentration parameter of cellulose ether within the range of 5-50% w/w in the liquid composition. This parameter optimization allows achieving adequate drug solubility enhancement while avoiding excessively high concentrations that would cause unmanageable viscosity increases and associated storage/transportation cost penalties.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs spray drying to create a solid dispersion copy or analog of the liquid composition. This solid dispersion form maintains the solubility-enhancing benefits of high cellulose ether content while eliminating the viscosity-related storage and transportation issues, as the solid form has negligible flowability problems.

Inventive Principle:
Principle #26Copying

3Stability of the object's composition

If cooling is used to prevent viscosity increase, then the storage stability is improved, but the storage complexity and costs increase

Engineering Contradiction:
Improveviscosity stabilityVSAvoidstorage infrastructure requirements
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent changes the formulation parameters by selecting low-viscosity cellulose ethers (10-100 cP at 2% concentration) and optimizing their concentration (5-50% w/w) with suitable organic diluents. This parameter optimization allows the liquid composition to maintain stable viscosity at room temperature storage, eliminating the need for refrigerated storage infrastructure and associated complexity.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS11000594B2Composition comprising an organic liquid diluent and a cellulose ether of very low viscosity
Publication Date: 2021.05.11 NUTRITION & BIOSCIENCES USA 1 LLC

AI summary

A liquid composition which comprises an organic liquid diluent and at least one non-ionic cellulose ether having a viscosity of up to 2.33 mPa·s, measured as a 2 wt.-% solution in water at 20° C., is stable over an extended time period. The liquid composition is useful for preparing a solid dispersion comprising at least one active ingredient in at least one cellulose ether by spray-drying. Alternatively a solid dispersion can be produced by blending and extruding at least one active ingredient, at least one cellulose ether having a viscosity of up to 2.33 mPa·s and optionally one or more adjuvants.