Chemical Structural Effects of Amphipathic and Water-soluble Phospholipid Polymers on Formulation of Solid Dispersions.

Abstract

For the polymeric carriers of solid dispersions, it is important that carriers themselves dissolve quickly and maintain the supersaturated state of amorphous drugs during their dissolution period to improve bioavailability. Amphipathic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers can be dissolved in water, owing to the extremely high hydrophilicity of the MPC units, and are used as an ideal feeder for drug molecules to form aggregates in aqueous conditions. We synthesized amphipathic MPC copolymers with different hydrophobic side chains and molar ratios of MPC units, and evaluated the effect of the polymers on dissolution rate and supersaturation maintenance of solid dispersions of indomethacin. In most of the water-soluble amphipathic MPC copolymers, "spring-parachute"-like dissolution behavior was observed, where the drug initially became supersaturated followed by slow precipitation. In particular, MPC copolymers with aromatic rings in their side chains or polymers with a high percentage of hydrophobic units remained in a supersaturated state for a longer period. In contrast, urethane groups, which form hydrogen bonds with drug molecules, could also interact with water and were not conducive to maintaining supersaturation. In addition, water solubility of the polymer is important for rapid dissolution.