High-Pressure Sterilization of Heat-Sensitive Pharmaceutical Preparations
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Solution Overview
Problem
Current sterilization techniques, such as terminal autoclaving, are inadequate for small particle dispersions of poorly soluble pharmaceutical compounds as they lead to chemical instability, aggregation, and degradation due to heat sensitivity, and traditional methods like gamma sterilization or ETO can compromise the integrity of solutions containing glucose or other sensitive components.
Innovation Solution
A high-pressure sterilization method that supplies heat energy and pressurizes systems above 0.25 MPa to achieve sterilization without significant degradation, maintaining the stability and efficacy of pharmaceutical preparations, including those with glucose, by ensuring rapid heat transfer and minimizing temperature exposure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If terminal autoclaving is used to sterilize small particle dispersions, then sterilization is achieved, but chemical instability and degradation occur due to heat sensitivity
Solution Approach 1:
The patent changes the sterilization parameters by using high pressure (greater than 0.25 MPa) combined with temperature, deviating from conventional atmospheric pressure autoclaving. This parameter modification enables sterilization at conditions that preserve the chemical stability of heat-sensitive pharmaceutical preparations while achieving the required sterility level
Solution Approach 2:
The patent implements a periodic sterilization cycle with distinct phases: heating phase, high-pressure sterilization phase, and pressure release phase. The periodic application of high pressure followed by pressure release allows for effective sterilization while minimizing continuous thermal exposure that would cause degradation
2Reliability
If high temperature sterilization is applied to ensure rapid heat transfer, then sterilization effectiveness is improved, but particle aggregation and growth occur
Solution Approach 1:
The patent modifies the sterilization parameters by introducing high pressure as a critical factor alongside temperature. This parameter change enables the system to achieve rapid heat transfer and effective sterilization while the high pressure prevents particle aggregation and growth that would otherwise occur at high temperatures
Solution Approach 2:
The patent uses high pressure as an intermediary factor that mediates between the conflicting requirements of rapid heat transfer for sterilization and prevention of particle aggregation. The high pressure acts as a protective force that allows thermal sterilization to proceed without causing the harmful aggregation of particles
3Stability of the object's composition
If surfactant cloud point modifiers are added to raise cloud point above 121°C, then particle stability during autoclaving is improved, but formulation complexity increases
Solution Approach 1:
The patent extracts and eliminates the need for surfactant cloud point modifiers by using high pressure sterilization. Instead of chemically modifying the surfactant system to raise its cloud point, the invention uses physical pressure to prevent cloud point precipitation, thereby simplifying the formulation while maintaining particle stability during sterilization
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 effectively sterilizes pharmaceutical preparations and solutions, including those with glucose, while maintaining their stability and efficacy, with glucose remaining substantially undegraded, and prevents aggregation and degradation of particles, ensuring sterility without compromising the system's usability.
Implementation Method 1
rapid adiabatic heating of the formulation during the compression step
Implementation Method 2
pressurizing the system in excess of 0.25 MPa for a period of time sufficient to make the system sterile
Data Source
AI summary
The present invention provides a process for sterilizing a system, preferably a pharmaceutical preparation such as a dispersion of small particles or droplets of a pharmaceutically active compound using high pressure terminal sterilization techniques and products therefrom.