Enabling isolation of an intrinsically amorphous API using a mesoporous carrier-assisted particle engineering...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Intrinsically amorphous active pharmaceutical ingredients (APIs) often present challenges in isolation and downstream processing due to poor physicochemical properties.
• Developing scalable and efficient methods for handling amorphous APIs is crucial for pharmaceutical development.

Purpose of the Study:

• To develop and optimize a mesoporous silica-assisted isolation approach for an amorphous API (Compound X).
• To enhance the physicochemical properties of the isolated API, facilitating drug product manufacturing.
• To demonstrate the scalability and utility of the developed process using advanced analytical tools.

Main Methods:

• Utilized mesoporous silica as a carrier for API isolation.
• Employed in-situ process analytical tools (PAT) to investigate critical process parameters.
• Systematically studied carrier type, solvent composition, API-to-carrier ratio, and anti-solvent addition.
• Scaled the optimized process from gram to 200 g scale in a 5 L reactor.

Main Results:

• Achieved efficient isolation of amorphous Compound X with improved flowability and bulk density at a 1:1 API-to-carrier ratio.
• Demonstrated uniform API deposition onto the carrier surface.
• Successfully scaled the process, confirming its feasibility for larger production.
• The co-processed material exhibited excellent compressibility, tabletability, and compatibility (CTC), enabling direct compression.
• Full drug release was observed in biorelevant media (FaSSIF-V1).

Conclusions:

• Carrier-assisted API isolation, particularly with mesoporous silica, offers significant advantages for amorphous compounds.
• Integration of PAT accelerates process development and optimization.
• Co-processed APIs simplify downstream drug product manufacturing, enabling direct compression.
• This strategy addresses key challenges in developing intrinsically amorphous APIs.