Structured Surfactant Suspension for Pharmaceutical Stability

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Solution Overview

Problem

Current pharmaceutical suspensions face challenges such as sedimentation, high viscosity, and instability, limiting their use for internal administration due to insolubility issues and the inability to suspend coarse particles effectively, while existing structured surfactant systems are not suitable for pharmaceutical and food applications due to high surfactant levels, taste, and temperature instability.

Innovation Solution

A mixture of a sugar ester or triterpenoid glycoside with a high HLB and a minor proportion of a fatty acid forms a robust, low viscosity, self-structuring system capable of suspending pharmaceutical active ingredients at reduced surfactant levels, which is tasteless and stable at high temperatures, using a composition comprising water, sugar, and surfactant with a surfactant component comprising a major portion of sugar ester or triterpenoid glycoside and a minor portion of fatty acid or lecithin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If thickeners (gums or polymers) are used to raise viscosity, then sedimentation is retarded, but the suspension is not stable and becomes unacceptably viscous

Engineering Contradiction:
Improvesuspension stabilityVSAvoidviscosity
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent changes the fundamental parameter of the suspending medium from a simple aqueous solution to a structured surfactant system with specific rheological properties. The surfactant concentration and HLB value are optimized to achieve the right balance between suspension stability and pourability, eliminating the need for excessive thickening agents.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses a composite surfactant system combining multiple surfactants with different HLB values (e.g., high HLB surfactant like sugar ester and low HLB surfactant) to create a structured system that provides both suspension stability and acceptable flow properties, avoiding the drawbacks of single-component thickeners.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If colloidal dispersions are used to prevent sedimentation, then particles remain suspended, but coarse particles cannot be dispersed and Ostwald ripening occurs

Engineering Contradiction:
Improvesuspension stabilityVSAvoidparticle size range
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent changes the particle size parameter that can be suspended by transitioning from colloidal systems (sub-micron) to structured surfactant systems that can immobilize larger non-colloidal particles through their rheological properties and yield point, preventing sedimentation across a broader particle size range.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If high concentrations of solids are suspended, then therapeutic dosing range is achieved, but the product becomes unacceptably viscous

Engineering Contradiction:
Improvesolid concentrationVSAvoidviscosity
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The invention changes the rheological parameters of the continuous phase by using structured surfactant systems with specific yield points and flow characteristics, enabling higher solid concentrations to be suspended without reaching unacceptably high viscosities, thus allowing adequate therapeutic dosing ranges.

Inventive Principle:
Principle #35Parameter changes

4Stability of the object's composition

If existing structured surfactant systems are used, then suspension stability is achieved, but high surfactant levels cause taste issues and temperature instability

Engineering Contradiction:
Improvesuspension stabilityVSAvoidtaste and temperature stability
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the HLB parameter of the surfactant system and adjusts surfactant concentration to achieve stable suspensions at lower levels, reducing taste issues. The surfactant selection and concentration are also optimized for temperature stability, preventing phase separation and maintaining suspension integrity across a wider temperature range.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses composite surfactant systems combining surfactants with complementary properties (different HLB values, temperature stability characteristics) to achieve both suspension stability and improved taste/temperature performance, leveraging the synergistic effects of multiple surfactant components.

Inventive Principle:
Principle #40Composite materials

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 system achieves stable suspension of non-colloidal particles for prolonged periods with minimal sedimentation, low viscosity, and improved flavor, allowing for effective pharmaceutical and veterinary use without the need for high surfactant concentrations or bent chain surfactants, thus overcoming the limitations of existing technologies.

Implementation Method 1

structured suspending systems depend on the rheological properties of the suspending medium to immobilise the particles, irrespective of size

Methodology Applied
Scientific EffectRheological properties:

Implementation Method 2

This requires the suspending medium to exhibit a yield point, which is higher than the sedimenting or creaming force exerted by the suspended particles

Methodology Applied
Scientific EffectYield point:

Implementation Method 3

The latter contain particles of about 1 micron or smaller, which are prevented from sedimenting by Brownian motion

Methodology Applied
Scientific EffectBrownian motion: Brownian Motion

Implementation Method 4

a mixture of a sugar ester or triterpenoid glycoside with a high HLB and a minor proportion of a fatty acid forms a robust, low viscosity system with suspending properties... which is tasteless and self-structuring in water

Methodology Applied
Scientific EffectSelf-structuring: Self-Assembly

Implementation Method 5

The structure reforms sufficiently rapidly to prevent sedimentation, once the agitation caused by the external stress has ceased

Methodology Applied
Scientific EffectRapid structure reform:

Data Source

PatentEP2254600B1Novel compositions and uses thereof
Publication Date: 2017.05.17 BIOSUSPENSIONS

AI summary

The present invention provides structured surfactant systems comprising water and from 0 to saturation of sugar, together with sufficient surfactant to form a structure capable of suspending solids, wherein the surfactant comprises a mixture of: (i) a major portion of at least one sugar ester and/or a triterpenoid glycoside (saponin) having an HLB greater than 10; and (ii) a minor portion of at least one fatty acid and/or lecithin. The invention further provides pharmaceutical compositions comprising a structured surfactant system of the invention and a pharmaceutical or veterinary active ingredient.