Optimizing drug nanoparticles release from amorphous solid dispersions: exceptional performance of poly(acrylic acid)...

Amorphous solid dispersions (ASDs) have been observed to release their active ingredients in an aqueous medium as drug-rich nanoparticles, leading to high apparent solubility and potential benefits for drug absorption. We have prepared the ASDs of lumefantrine with 10 polymers and tested their release of drug-rich nanoparticles in 0.1 % sodium dodecyl sulfate. Poly(acrylic acid) (PAA) significantly outperforms the other polymers in reaching the highest apparent solubility through a 0.2 μm filter, and its outperformance persists as drug loading increases from 25 % to 50 %, without sudden decline of release reported for some formulations. The PAA formulation releases its drug cargo as nanoparticles that are stable for at least 8 h, sufficient for transit through the gastrointestinal tract. The nanoparticles released by PAA are the smallest (∼10 nm according to volume mean) of the formulations tested. The exceptional performance of PAA is likely due to its high aqueous solubility, high acidic-group density, and ability to interact with ionic species during dissolution. Our finding suggests that PAA is a promising and presently underutilized polymer for amorphous formulations.