Amorphous pharmaceuticals such as acetaminophen offer enhanced solubility and bioavailability compared to their crystalline counterparts, yet their tendency to recrystallize limits long-term stability and therapeutic effectiveness. This study investigates the crystallization kinetics of acetaminophen across temperatures and under nanoconfinement to better understand how spatial restriction influences molecular mobility and crystal growth. Thin films of acetaminophen were prepared by spin-casting on silicon substrates, with nanoconfined samples fabricated via capillary rise infiltration into silica nanoparticle layers (45 nm). Crystal growth was monitored in situ using optical microscopy under temperature-controlled conditions, and growth rates were determined from time-resolved imaging.

Results show that bulk acetaminophen exhibits maximum crystallization rates near 353 K, while nanoconfined films crystallize significantly slower, peaking around 373 K. Across all temperatures, confined samples display growth rates approximately 10⁴ times lower than bulk, demonstrating strong kinetic suppression due to confinement. These findings indicate that nanoconfinement effectively stabilizes the amorphous phase by reducing molecular mobility and delaying crystallization onset.

This work underscores the potential of nanoconfinement as a strategy for improving the physical stability of amorphous pharmaceuticals. Future studies will expand to varying pore sizes and extended temperature ranges to further elucidate confinement effects on molecular dynamics and drug performance.