Glucocorticosteroid Suspension Sterilization via Controlled Heating
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Solution Overview
Problem
Current sterilization methods for glucocorticosteroids often result in unfavorable changes to the drug profile, including loss of activity, increased degradation, and unacceptable changes in particle size, particularly for suspension formulations intended for inhalation, with residual toxic compounds and significant degradation being major concerns.
Innovation Solution
A method involving heating a glucocorticosteroid suspension with a surfactant in a mixing vessel, re-circulating it via a homogenizer for sterilization, and subsequently mixing with sterile water or excipient liquid to maintain sterility and prevent particle growth, using a specific apparatus and process to ensure effective sterilization without excessive degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heat sterilization is applied to glucocorticosteroid suspensions, then sterility is achieved, but particle size increases and drug degradation occurs
Solution Approach 1:
The suspension is pre-heated to 50-95°C before sterilization and maintained at this temperature during sterilization, then rapidly cooled. This preliminary temperature control prevents excessive particle growth and degradation while achieving sterility through the controlled thermal process.
Solution Approach 2:
The sterilization process uses specific temperature ranges (50-95°C for 15-120 minutes) rather than traditional autoclaving conditions. By optimizing and controlling the temperature and time parameters, the process achieves sterility while minimizing particle size increase and drug degradation.
2Reliability
If conventional sterilization methods are used, then microbial contamination is eliminated, but loss of drug activity and increased degradation products occur
Solution Approach 1:
The process uses lower temperature ranges (50-95°C) combined with extended time (15-120 minutes) compared to traditional sterilization. This parameter optimization reduces thermal degradation and maintains drug activity while still achieving complete sterility.
Solution Approach 2:
The sterilization involves heating to a specific temperature range, maintaining it for a controlled period, then rapidly cooling. This periodic thermal action achieves microbial elimination while limiting the total exposure time to degrading conditions, preserving drug activity.
3Reliability
If ethylene oxide sterilization is used, then sterility is achieved, but toxic residues remain above acceptable limits
Solution Approach 1:
The process replaces chemical sterilization (ethylene oxide) with a thermal sterilization method using controlled heating and cooling. This substitution eliminates toxic chemical residues while achieving the same sterility outcome through physical thermal means.
4Reliability
If irradiation sterilization is applied to micronized glucocorticosteroids, then sterility is achieved, but significant degradation occurs
Solution Approach 1:
The process replaces irradiation sterilization with thermal sterilization using controlled heating to 50-95°C. This substitution maintains drug integrity and minimizes degradation while achieving complete sterility through thermal means rather than radiation.
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 glucocorticosteroid suspensions while minimizing particle size changes and residual toxic compounds, ensuring pharmaceutical acceptability and maintaining the drug's activity, thus addressing the limitations of existing methods.
Implementation Method 1
re-circulating the glucocorticosteroid suspension via a homogenizer before, during and/or after step (i)
Implementation Method 2
heating a glucocorticosteroid suspension comprising a glucocorticosteroid, water and a surfactant in a mixing vessel to sterilize the glucocorticosteroid suspension
Data Source
AI summary
The present invention provides a method for preparing a sterile suspension of a glucocorticosteroid. The glucocorticosteroids used in the invention are preferably antiinflammatory glucocorticosteroids. By making the last stage of product preparation be the sterilization process, the potential for contamination during manufacture and heat degradation of products is greatly reduced.