For years, pharmaceutical scientists have sought to enhance bioavailability by transforming drugs from their crystalline state into more soluble, amorphous forms. Traditional methods like spray drying, though effective, rely on solvents that introduce complexity, safety concerns, and post-processing burdens. Ball milling offers a solvent-free alternative but is slow, inconsistent, and difficult to scale.
Enter a new method: dry amorphization by twin-screw extrusion (TSE). This innovative approach promises not only solvent-free production but also continuous processing, a much-needed advancement in the pharmaceutical industry.
Dr. Margarethe Richter, Application Specialist at Thermo Fisher Scientific, recently discussed the challenges of amorphization and the significance of this new method.
“Amorphous drugs dissolve more easily in water,” she explained. “This is crucial for bioavailability, especially with today’s complex molecules.”
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While the principle of amorphization isn't new, the tools are. Dr. Richter and her team partnered with Grace to utilize mesoporous silica, a material with an enormous internal surface area ideal for physically trapping drug molecules. By feeding a 50:50 blend of API and silica into a lab-scale twin-screw extruder (Thermo Scientific™ Pharma 11 Twin-Screw Extruder), they generated the mechanical energy needed to break down the crystalline structure—without high heat and without solvents.
This process differs from traditional hot melt extrusion. The system was configured more like a granulator, with no die on the end and no need for liquid binders. The twin screws, intermeshing and co-rotating, applied shear forces directly to the blend. The relatively soft silica could be milled in-line, eliminating the need for pre-treatment or secondary equipment.
“We found that kneading intensity and screw configuration were essential,” Dr. Richter noted. “Once you hit the right shear level, the API begins to amorphize—even at lower temperatures.”
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Verification of the process required more than just observing powder fall from the extruder. The team used DSC, XRD, and SEM to confirm the loss of crystallinity and reduction in particle size. The data confirmed that the process worked—and worked continuously.
Challenges remain, including long-term stability, recrystallization risk, and formulation optimization. However, the implications are clear: TSE-based dry amorphization offers scalable, solvent-free drug manufacturing with tight process control and minimal post-processing.
As pharmaceutical development moves toward continuous platforms, the ability to combine granulation, milling, and amorphization in a single, dry step represents a significant advancement.
Watch our full interview with Dr. Margarethe Richter or speak to one of our experts to learn more about this process, the supporting data, and how you can adapt it in your own lab or manufacturing setup.
