Thiswork evaluates the feasibility of the supercritical enhancedatomization (SEA) process to improve stability and delivery of activepharmaceutical ingredients (APIs). This process was used to generatedistinct microcomposites of pure theophylline (TPL), an API model,the theophylline-saccharin (TPL-SAC) cocrystal, and dispersions ofeach crystalline form in hydrogenated palm oil (HPO), TPL-HPO andTPL-SAC-HPO. The formation of the TPL-SAC cocrystal within the HPOsuggests that the cocrystallization step anticipates the lipid dispersionduring the formation of the microcomposites. The TPL-SAC cocrystalextended the TPL stability at 92% relative humidity by over 6 months,contrary to that of raw TPL, which converted into a monohydrate aftera few days only, even when dispersed into HPO. The TPL-SAC cocrystalslowed the TPL release from the lipid particles, which is explainedby its higher stability toward hydration. The feasibility of the cocrystalmicrocomposites for therapeutic application was evaluated by estimatingthe plasmatic concentration of TPL using a pharmacokinetic model (onecompartment approach). This model revealed that the small therapeuticconcentration window and high elimination rate of TPL raises seriouslimitations to control the TPL release. The microcomposites were ableto attenuate the TPL burst effect and improve stability toward hydrationbut could not extend significantly its delivery. [ABSTRACT FROM AUTHOR]