Can you please introduce yourself and your role at Thermo Fisher Scientific?
My name is Margarethe Richter, Pharma Application Specialist at Thermo Fisher Scientific. I develop and test new pharmaceutical applications for our extruders, helping customers scale their processes. I work with a range of techniques, from hot melt extrusion and twin screw granulation to diverse dosage forms.
Why is drug amorphization important in pharmaceutical development?
Amorphization is a great method for enhancing a drug’s bioavailability. Many new molecules are large and poorly soluble. By converting them to an amorphous state, they dissolve more easily in water and permeate biological membranes more readily, benefiting efficacy.
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What are the current techniques for achieving amorphous drug states?
Two common techniques are spray drying and hot melt extrusion. In spray drying, both the API and excipient are dissolved in a solvent, which is then evaporated to produce an amorphous powder. While effective, this method can leave behind solvent residues and poses handling challenges. Hot melt extrusion, on the other hand, eliminates the need for solvents but relies on heat-stable APIs and excipients to prevent molecular degradation.
How does mesoporous silica offer a novel route to amorphization?
Mesoporous silica provides an innovative pathway to amorphization by stabilizing the drug within its porous structure. In this method, the API is milled together with mesoporous silica, allowing the drug to remain in an amorphous state as it becomes embedded in the silica’s pores. This process means that we don't need to use heat and solvents, minimizing the risk of degradation and contamination. However, traditional ball milling, often used to combine the materials, is inherently slow, batch-based, and challenging to scale for large-scale manufacturing.
Can twin screw granulation (TSG) be adapted for this silica‑based amorphization?
Yes. We set up a co-rotating twin screw extruder in granulation mode, using an open barrel with no die. The mechanical shear from the screws effectively broke down the silica. Testing with a medium-grade steel setup confirmed that the silica–API blend was successfully fragmented.
How did you verify the process achieved full amorphization?
We used differential scanning calorimetry (DSC) to detect crystalline melting points and X‑ray diffraction (XRD) to check for remaining crystallinity. We ran challenging 50:50 silica:API blends and also captured SEM images that confirmed particle size reduction and loss of crystals.
What are the advantages of using TSG for this process?
TSG offers continuous processing with flexible formulation integration via multiple feed ports. This setup enabled rapid screening of screw configurations and process parameters—adjusting feed rates and screw speeds on‑the‑fly without restarting batches. Only customizing the screw design requires brief downtime.
How critical is screw configuration?
Extremely. High‑shear, high‑energy mixing is essential to fragment crystals and promote absorption into silica pores. We optimized configurations to deliver the necessary mechanical energy, as detailed in our published data.
About Margarethe Richter
Margarethe Richter is a Pharma Application Specialist at Thermo Fisher Scientific, focusing on pharmaceutical processes via twin screw and hot melt extrusion technologies. She holds a degree in Pharmaceutical Sciences.
At Thermo Fisher, Margarethe has spearheaded projects advancing solvent-free drug amorphization and worked closely with partners such as Grace on silica‑based formulations. Her published work in MDPI explores continuous twin screw granulation for amorphous drug delivery, contributing valuable insights into scalable pharmaceutical manufacturing.
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