The underestimated contribution of the solvent to the phase behavior of highly drug loaded amorphous solid dispersions

• Published in: International journal of pharmaceutics 2021-11, Vol.609, p.121201-121201, Article 121201
• Main Authors: Dedroog, Sien, Boel, Eline, Kindts, Célestine, Appeltans, Bernard, Van den Mooter, Guy
• Format: Article
• Language: English
• Subjects: Amorphous solid dispersions; Film casting - Solvent; Kinetic stabilization; Kinetic trapping; Spray drying
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.121201

[Display omitted] In spite of the fact that spray drying is widely applied for the formulation of amorphous solid dispersions (ASDs), the influence of the solvent on the physical properties of the ASDs is still not completely understood. Therefore, the impact of organic solvents on the kinetic stabilization of drug components in a polymer matrix prepared by either film casting or spray drying was investigated. One polymer, PVPVA 64, together with one of four poorly water soluble drugs, naproxen, indomethacin, fenofibrate or diazepam, were film casted and spray dried using either methanol, ethanol, isopropanol, acetonitrile, acetone, dichloromethane or ethyl acetate. For every combination, the highest drug loading that could be formulated as a single amorphous phase was established. The solvent determined the maximum amount of drug that could be kinetically trapped in the polymer matrix and thereby the extent of kinetic stabilization. These maximum drug loadings were compared to the thermodynamic solubilities of the drugs in the seven solvents. Generally, there was no relation between the thermodynamic solubility of a drug and its highest drug loading attained using the same solvent. Hence, the contribution of the solvent to the generation of a supersaturated state should not be underestimated.