Poloxamer Solution Sterilization via Pressure Control

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Solution Overview

Problem

Current methods for sterilizing poloxamer solutions using thermal steam under pressure often result in irreversible gel formation due to high temperatures, which complicates the process and does not ensure complete sterility, leading to prolonged recovery times and high production costs.

Innovation Solution

A method involving sterilizing filtration of aqueous poloxamer solutions followed by thermal sterilization with steam under pressure between 82.4 and 107.8 kPa, with controlled cooling to reduce gel formation time and ensure sterility, using sterile containers and reducing sterilization pressure to 82.4-107.8 kPa after the process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If thermal sterilization with steam under pressure at typical sterilization temperature (around 120°C) is applied to poloxamer solutions, then sterility is ensured, but irreversible gel formation occurs because the sterilization temperature is 2-3 times higher than the gel formation temperature

Engineering Contradiction:
ImprovesterilityVSAvoidsolution transparency
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention changes the pressure parameter during thermal sterilization from typical high pressure (107.9-117.7 kPa) to reduced pressure (82.4-107.8 kPa). This parameter change allows sterilization at lower temperatures that do not trigger gel formation, thus maintaining solution transparency while ensuring sterility

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention applies preliminary anti-action by conducting sterilizing filtration before thermal sterilization. This preliminary step removes potential gel-forming contaminants, allowing subsequent thermal processing at controlled pressures without risking irreversible gelation

Inventive Principle:
Principle #9Preliminary anti-action

2Reliability

If typical thermal sterilization pressure (107.9-117.7 kPa) is used, then sterilization is effective, but the recovery time from gel formation is prolonged

Engineering Contradiction:
Improvesterilization effectivenessVSAvoidrecovery time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention reduces the pressure parameter during thermal sterilization to 82.4-107.8 kPa, which corresponds to lower temperatures. This prevents gel formation during sterilization, eliminating the need for prolonged recovery time and thus reducing the overall process time while maintaining sterilization effectiveness

Inventive Principle:
Principle #35Parameter changes

3Reliability

If sterilizing filtration is performed separately from container filling, then sterility is achieved, but the process complexity and production time increase

Engineering Contradiction:
Improvesterility levelVSAvoidprocess steps
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention merges sterilizing filtration and container filling into a single simultaneous operation. The filtration system is directly connected to the filling apparatus, allowing the solution to be filtered and filled in one continuous process, thereby reducing process complexity and production time while maintaining sterility

Inventive Principle:
Principle #5Merging (Combining)

4Reliability

If high pressure thermal sterilization is applied to ensure complete sterility, then pyrogenic impurities are removed, but the gel formation temperature is exceeded causing irreversible gelation

Engineering Contradiction:
ImprovedepyrogenationVSAvoidsolution homogeneity
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention changes the pressure parameter to a reduced range (82.4-107.8 kPa) during thermal sterilization, which corresponds to lower temperatures that remain below the gel formation temperature. This allows effective depyrogenation and sterilization while preventing irreversible gelation and maintaining solution homogeneity

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

This method significantly reduces the time required to recover the poloxamer solution after gel formation and the overall thermal sterilization process, ensuring sterility and maintaining solution transparency, thus improving the efficiency and cost-effectiveness of the process.

Implementation Method 1

thermal sterilization with steam under pressure

Methodology Applied
Scientific EffectThermal heating: Heating

Implementation Method 2

thermal sterilization with steam under pressure between 82.4 and 107.8 kPa

Methodology Applied
Scientific EffectPressure control: Pressure Increase

Implementation Method 3

controlled cooling to reduce gel formation time

Methodology Applied
Scientific EffectThermal cooling: Cooling

Implementation Method 4

sterilizing filtration of aqueous poloxamer solutions

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentUS11383870B2Thermal method for sterilizing poloxamer comprising liquid drugs
Publication Date: 2022.07.12 ARSHINTSEVA ELENA VALENTINOVNA

AI summary

The invention relates to chemical and pharmaceutical industry, in particular to technologies of obtaining sterile drugs, drug substances and cosmetic products used in the form of solutions or emulsions, and comprising poloxamer. The thermal method for sterilizing aqueous poloxamer solutions is provided, the method including: dissolving a poloxamer in water for injection; performing the sterilizing filtration of the aqueous poloxamer solution simultaneously with filling sterile containers with the filtered poloxamer solution; sealing the containers containing the poloxamer solution; applying a thermal sterilization with steam under pressure to the containers containing the poloxamer solution, and cooling them, wherein the thermal sterilization of the containers containing the poloxamer solution with steam under pressure is performed under the pressure between 82.4 and 107.8 kPa.