Improvement of Oral Absorption of Poorly Water-Soluble Drugs by Solid Dispersions with Amphiphilic Phospholipid Polymer

Solid dispersions are one of methods for solubilizing water-insoluble drugs. To enhance the bioavailability, maintenance of the supersaturated state and absorption of the dissolved drug in the gastrointestinal tract are important. We designed and synthesized amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers as carriers for solid dispersions and evaluated the dissolution behavior in test solutions with dif-ferent pH and additives. Solid dispersion of troglitazone with amphiphilic MPC copolymers having both aro-matic rings and urethane bonds in the side chains showed rapid dissolution and excellent supersaturation maintenance. It was indicated that the balance between the interactions with drug molecules and the water affinity of the polymer should be considered when carriers for solid dispersions are designed. In addition, cell membrane permeability of the solid dispersion with the amphiphilic MPC copolymer was evaluated by the Dissolution / Permeation system, which consists of two liquid chambers and a monolayer of epithelial cells that mimics the intestinal dissolution and permeation process. Further, blood concentration of the drug when solid dispersions were orally administered in mice was also evaluated. The cell membrane permeabil-ity and oral absorbability were significantly improved, compared to the solid dispersions with poly(N-vinyl-pyrrolidone) and suspension or solution of crystalline troglitazone.(c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

Solid dispersions are an effective method for solubilizing water-insoluble drugs, and the use of amphiphilic MPC copolymers as carriers can significantly improve dissolution and supersaturation maintenance. Furthermore, these copolymers enhance cell membrane permeability and oral absorbability.