Aluminum Hydroxide Suspension Stability via Composite Cellulose Agents

Solution Overview

Problem

Existing suspensions of aluminum hydroxide and magnesium hydroxide face issues with sedimentation rate and texture, requiring high amounts of suspending agents that can lead to bioavailability changes and microbial contamination, with prior art lacking effective solutions for improving these aspects.

Innovation Solution

Aqueous suspension composition using a mixed suspending agent combination of hydroxypropyl methylcellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, and carrageenan, along with an antifoaming agent, to enhance sedimentation rate and texture, while minimizing the use of suspending agents and preventing microbial contamination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If a large amount of suspending agent is used to stabilize the suspension, then the suspension stability is improved, but the bioavailability is changed and microbial contamination risk increases

Engineering Contradiction:

Improvesuspension stabilityVSAvoidbioavailability

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent uses a composite suspending agent system combining hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC) in specific ratios (0.3-1.0% HPMC and 0.1-0.5% HEC). This composite approach provides synergistic effects where HPMC contributes to viscosity and suspension stability while HEC enables low-temperature sterilization, achieving both stability and safety without compromising bioavailability

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent optimizes the concentration parameters of suspending agents to precise ranges (HPMC: 0.3-1.0%, HEC: 0.1-0.5%) to achieve the minimum effective dosage. This parameter optimization ensures sufficient suspension stability while minimizing the total amount of suspending agent, thereby preventing bioavailability changes and reducing microbial contamination risk

Inventive Principle:

Principle #35Parameter changes

2Device complexity

If a single suspending agent is used to simplify the formulation, then the formulation complexity is reduced, but the sedimentation rate and texture are insufficient

Engineering Contradiction:

Improveformulation complexityVSAvoidsedimentation rate

Core Design Contradiction:

Device complexityVSStability of the object's composition

Solution Approach 1:

The patent employs a composite suspending agent system combining hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC) in specific ratios (0.3-1.0% HPMC and 0.1-0.5% HEC). This composite approach provides synergistic effects where HPMC contributes to viscosity and suspension stability while HEC enables low-temperature sterilization, achieving both stability and safety without compromising bioavailability

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent optimizes the concentration parameters of suspending agents to precise ranges (HPMC: 0.3-1.0%, HEC: 0.1-0.5%) to achieve the minimum effective dosage. This parameter optimization ensures sufficient suspension stability while minimizing the total amount of suspending agent, thereby preventing bioavailability changes and reducing microbial contamination risk

Inventive Principle:

Principle #35Parameter changes

3Adaptability or versatility

If hydroxypropyl methylcellulose is used as suspending agent to ensure miscibility with metal ions, then the compatibility is improved, but thermal gelation occurs during pasteurization

Engineering Contradiction:

Improvecompatibility with metal ionsVSAvoidthermal gelation

Core Design Contradiction:

Adaptability or versatilityVSTemperature

Solution Approach 1:

The patent introduces hydroxyethyl cellulose (HEC) as a complementary suspending agent that acts as a mediator. HEC has superior thermal stability and does not undergo gelation during pasteurization, while still maintaining compatibility with metal ions. The combination of HPMC and HEC in specific ratios allows the formulation to benefit from both agents' properties, ensuring ion compatibility and thermal stability

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent uses a composite suspending agent system combining hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC) in specific ratios (0.3-1.0% HPMC and 0.1-0.5% HEC). This composite approach provides synergistic effects where HPMC contributes to viscosity and suspension stability while HEC enables low-temperature sterilization, achieving both stability and safety without compromising bioavailability

Inventive Principle:

Principle #40Composite materials

4Device complexity

If the suspension is left untreated to maintain simplicity, then the formulation complexity is reduced, but the solid particles settle and form hard sediment

Engineering Contradiction:

Improveformulation complexityVSAvoidparticle settlement

Core Design Contradiction:

Device complexityVSStability of the object's composition

Solution Approach 1:

The patent uses a composite suspending agent system combining hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC) in specific ratios (0.3-1.0% HPMC and 0.1-0.5% HEC). This composite approach provides synergistic effects where HPMC contributes to viscosity and suspension stability while HEC enables low-temperature sterilization, achieving both stability and safety without compromising bioavailability

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent optimizes the concentration parameters of suspending agents to precise ranges (HPMC: 0.3-1.0%, HEC: 0.1-0.5%) to achieve the minimum effective dosage. This parameter optimization ensures sufficient suspension stability while minimizing the total amount of suspending agent, thereby preventing bioavailability changes and reducing microbial contamination risk

Inventive Principle:

Principle #35Parameter changes

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 composition achieves a sedimentation rate of 0.97 to 1, ensuring physical stability and bioavailability, with an improved texture that increases patient compliance, meeting Pharmacopoeia requirements and maintaining effective bioavailability.

Implementation Method 1

the mixed suspending agent is a mixture of hydroxypropyl methylcellulose, microcrystalline cellulose, sodium carboxymethyl cellulose and carrageenan

Methodology Applied

Scientific EffectViscosifying effect of cellulose-based suspending agents:

Implementation Method 2

insoluble aluminum hydroxide and magnesium hydroxide do not easily settle, do not form a cake, and are easily redispersed

Methodology Applied

Scientific EffectSedimentation prevention through suspending action: Suspension

Data Source

PatentEP3610857B1Suspension comprising aluminum hydroxide and magnesium hydroxide and preparation method therefor

Publication Date: 2022.02.09 DAEWOONG PHARM CO LTD

AI summary

The present invention provides a suspension comprising aluminum hydroxide and magnesium hydroxide and a method of preparing the same. The aqueous suspension composition according to the present invention ensures an excellent sedimentation rate by using a mixed suspending agent with a specific composition, so that insoluble aluminum hydroxide and magnesium hydroxide do not easily settle, do not form a cake, and are easily redispersed. Since the aqueous suspension composition having an excellent sedimentation rate has not only physical stability, but also forms a homogeneous dispersion system, the reproducibility or effectiveness of bioavailability may be ensured. In addition, the aqueous suspension composition according to the present invention provides an excellent texture, and thus patient compliance increases.