Poor aqueous solubility remains a major limitation for the oral bioavailability of molecules such as felodipine (FDP), necessitating formulation strategies that enhance drug dissolution while remaining compatible with scalable, solvent-free processing. In this study, solid dispersions (SDs) of FDP were prepared using an organic solvent-free supercritical carbon dioxide (scCO2) process with four grades of polyethylene glycol (PEG 4K, 6K, 10K, and 20K) at drug loadings of 10, 20, and 30% w/w. The influence of PEG molecular weight, drug loading, and scCO2 processing conditions on the solid-state properties and dissolution behavior of FDP was investigated. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed a substantial reduction in FDP crystallinity, indicative of partial or extensive amorphization, dependent on polymer grade and processing temperature. All SDs showed markedly enhanced dissolution compared with crystalline FDP and corresponding physical mixtures, with PEG 4K SDs processed at 45 °C and PEG 20K SDs processed at 60 °C exhibiting the most pronounced improvements. Optimized SDs were subsequently incorporated into orally disintegrating tablets (ODTs), which retained the enhanced dissolution performance of the parent SDs, demonstrating that tabletting did not compromise drug release. While both PEG 4K- and PEG 20Kbased ODTs showed rapid dissolution, PEG 20K formulations exhibited superior mechanical integrity, identifying 30% w/w drugloaded PEG 20K SDs as the most suitable system for ODT development. Overall, this study demonstrates a green, solvent-free scCO2-based strategy for producing high-performance solid dispersions and their successful translation into ODTs for poorly watersoluble drugs.
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