Sterilizable Particle-Size Reduction Apparatus for Nebulizer Suspensions
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Solution Overview
Problem
Current particle-size reduction apparatuses for pharmaceutical suspensions, such as those used in nebulizers, face challenges with sterilization due to high pressure requirements and the risk of blockages, which can compromise sterility and affect particle size distribution, particularly for drugs like Budesonide that are sensitive to temperature and pressure.
Innovation Solution
A sterilizable particle-size reduction apparatus with larger flow passage cross-sectional areas (not less than 3.1×10^4 μm^2) and lower pressure operation (up to 69 MPa or 10,000 psi), allowing for effective comminution of particles while minimizing the risk of blockages and ensuring sterility, using a diaphragm pump and specific valve configurations to maintain sterility and prevent contamination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard sterilisation (raising temperature to 121°C for 15 minutes) is used, then sterility is achieved, but the formulation components are destroyed and particle size is altered
Solution Approach 1:
The invention changes the sterilisation parameter from thermal (121°C for 15 minutes) to chemical (ethylene oxide gas), allowing sterilisation without thermal degradation of the formulation components and particle size alteration
Solution Approach 2:
The invention uses an intermediary sterile filter (0.2 μm pore size) to separate sterilised suspension from unsterilised components, enabling the suspension to be sterilised without subjecting all formulation components to harsh sterilisation conditions
2Manufacturing precision
If particle-size reduction apparatus operates at high pressure, then effective comminution is achieved, but the risk of blockages increases and sterility is compromised
Solution Approach 1:
The invention changes the operating pressure parameter from high pressure to low pressure (atmospheric or slightly above), reducing the risk of blockages and sterility compromise while still achieving effective particle size reduction through extended processing time and multiple passes
Solution Approach 2:
The invention uses continuous circulation and multiple passes through the particle-size reduction apparatus at low pressure, achieving cumulative particle size reduction without the need for high pressure that would compromise sterility
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 method achieves acceptable particle size reduction and distribution with reduced pressure, enabling the production of sterile suspensions that meet regulatory standards, such as a 6-log reduction in bacterial spores, and allows for efficient processing of larger volumes of suspension without compromising sterility.
Implementation Method 1
an intensifier for forcing the suspension through the flow passage of the interaction chamber
Implementation Method 2
the transverse cross-sectional area of said flow passage is not less than 3.1×10^4 μm^2
Implementation Method 3
The sterilisation of suspensions raises particular problems. The standard means of sterilisation—that is, the raising of the temperature of the formulation to 121° C. for 15 minutes
Implementation Method 4
the desired biological activity of the formulation commonly requires that the mass median diameter of particles of the drug lie within a narrow range (average diameter typically less than 5 μm)
Data Source
AI summary
A sterilisable particle-size reduction apparatus, component parts thereof and a method of sterilising and validating sterility thereof are provided. Also provided is use thereof to prepare sterile suspensions of drugs.