Process Controlled Polymorphic Phase Transformation in Crystalline Solid Dispersions: Impact of Temperature, Pressure, and Shear Stress
Bibliographic record
Abstract
Understanding the processing boundaries to generate crystalline solid dispersions (CSDs) containing metastable polymorphs remains an untapped challenge for the application of hot-melt extrusion (HME) and three-dimensional printing (3DP) as polymer-based formulation approaches. Hence, to successfully implement CSDs as alternative solid dosage formulations, the effect of critical process parameters (CPPs) on potential polymorphic phase transformations (PPTs) needs to be examined. This study extends the current knowledge on the influence of CPPs through temperature–pressure–shear simulated extrusion (TPSS-E) using the model system flufenamic acid (FFA) and poly(ethylene glycol) (PEG). The TPSS-E results revealed a significant reduction in the average PPT induction time (53%) compared to previous temperature–pressure simulated-extrusion (TPS-E) studies without shear stress. However, TPSS-E control experiments performed at 25 °C showed no PPT. This suggests that temperature is the most critical parameter in determining whether a PPT will occur, while pressure and shear stress significantly accelerate the PPT kinetics from the metastable (FFA III) to the stable form (FFA I) at elevated temperatures. These results demonstrate that for an enantiotropic system like FFA forms I and III (transition point = 42 °C), it is possible to control the metastable polymorph in CSDs during extrusion processes if the thermodynamic and kinetic boundaries, the CPPs, and material attributes of the drug-polymer system are well understood and controlled. The work presented here expands on the application of HME and 3DP as polymer-based formulation strategies for CSDs containing metastable polymorphs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".