Enhancing Atorvastatin In Vivo Oral Bioavailability in the Presence of Inflammatory Bowel Disease and Irritable Bowel Syndrome Using Supercritical Fluid Technology Guided by wbPBPK Modeling in Rat and Human

An overview on the application of supercritical carbon dioxide for the processing of pharmaceuticals

“…These shortcomings can be overcome by utilization of the scCO2 technology, which allows the drug formulation preparation in the absence of oxygen, reducing the possibility of oxidative degradation, and results in a product with no residual organic solvent (14,22). Moreover, scCO2 technology solved drying issues and issues related to heat liability (24,25).…”

“…PVP polyvinylpyrrolidone; HPMC hydroxypropyl methylcellulose; Soluplus ®  polyvinyl acetate and polyvinyl caprolactam copolymer; Eudragit ®  poly-(N-dimethylaminoethyl methacrylate-co-methyl methacrylate-co-butyl methacrylate; HPMCAS hydroxypropyl methylcellulose acetate succinate; PEG polyethyleneglycol Alternatively, methanol or ethanol can be added to the polymer-drug mixture before exposure to scCO2 (19,20,25). Alsmadi et al (25) reported that this enabled the formation of a hydrogen bond between the carbonyl group of Soluplus ® and the hydroxyl group of atorvastatin, which led to a loss of atorvastatin crystalline form during exposure to scCO2. As a result, the dissolution of atorvastatin increased by more than 20-fold (from 61.6 to 1305.0 μg/mL) when tested in vitro.…”