Influence of carbon dioxide on the phase behavior of pharmaceutical drug‐polymer dispersions

Abstract

The formulation as amorphous solid dispersion (ASD) addresses recent challenges in the oral administration of poorly-soluble drugs by embedding them in highly-soluble carrier polymers. In this context, utilizing CO2 as a processing agent is an innovative strategy to facilitate the dissolution of the drug in the polymer at comparatively low temperatures without the use of any organic solvents. Within this study, the influence of CO2 on the phase behavior of ASD formulations is investigated. Therefore, high-pressure differential scanning calorimetry is applied to evaluate the dissolution of the drugs in the polymers and the glass transition temperatures under CO2 of four formulations containing the drugs acetaminophen and itraconazole as well as the polymers Soluplus and vinylpyrrolidone/vinyl acetate copolymer. The glass transition temperatures of the ASD formulations decrease with CO2 fraction dissolved in the polymer. The extent of Tg reduction is related to the spatial structure and intermolecular interactions of the polymers. Furthermore, the sorption of CO2 accelerates the diffusion of the drugs in the plasticized polymers. However, phase separation is observed in some formulations under CO2 loading which has an impact on the stability of the ASD and has to be considered in process design.