Glycopyrrolate Dry Powder Conditioning After Co-Jet Milling
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Solution Overview
Problem
Glycopyrrolate formulations face stability issues due to the generation of amorphous material during micronization, leading to physical instability and poor aerosol performance.
Innovation Solution
A method involving co-jet milling unmicronized glycopyrrolate with magnesium stearate in a desiccated environment followed by controlled humidity and temperature conditioning to convert amorphous surfaces to crystalline surfaces, resulting in a stable dry powder formulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If conventional micronisation process is used to reduce particle size, then particle size is reduced to inhalable range, but amorphous material is generated on particle surfaces leading to physical instability
Solution Approach 1:
The patent applies preliminary action by performing a conditioning step immediately after micronisation to address the amorphous material issue before it causes instability. The conditioned powder is then used in the final formulation, preventing the amorphous regions from leading to physical instability during storage and use.
Solution Approach 2:
The patent utilizes parameter changes by subjecting the micronised powder to specific temperature and humidity conditions during the conditioning step. These controlled environmental parameter changes promote crystallisation of the amorphous material, converting it back to stable crystalline form while maintaining the reduced particle size.
2Productivity
If high-energy milling is used to break particles to appropriate size, then particles are reduced to inhalable range, but non-crystalline material is generated on particle surfaces
Solution Approach 1:
The patent converts the harmful effect of high-energy milling (which creates amorphous material) into a beneficial process by using the resulting amorphous material as a target for controlled crystallisation during the conditioning step. The amorphous regions formed during milling are then deliberately converted back to crystalline form through the conditioning process, eliminating the instability issue.
3Loss of time
If micronised glycopyrrolate is used immediately after milling, then processing time is minimized, but physical instability occurs due to amorphous material
Solution Approach 1:
The patent applies preliminary action by performing the conditioning step as an immediate follow-up to micronisation, before the powder is used in the final formulation. This preliminary conditioning prevents physical instability from developing during subsequent storage and handling, ensuring formulation reliability without requiring extended processing time.
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 process achieves a stable particle size distribution with minimal amorphous material, improving aerosol performance and reducing the fraction of particles greater than 10 µm, ensuring consistent and efficient delivery.
Implementation Method 1
a conditioning step which includes exposure of the micronized composite particles to humidity at temperatures between 5°C to 88°C for at least 60 minutes
Data Source
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AI summary
A method and formulation is disclosed for making a pharmaceutical composition for pulmonary administration comprising co-jet milling glycopyrrolate and magnesium stearate, wherein the co-jet milled glycopyrrolate and magnesium stearate is then subjected to a conditioning step which includes exposure of the co-jet milled glycopyrrolate and magnesium stearate to humidity.