Tri-block polymer with interfacial layer formation ability and its use in maintaining supersaturated drug solution after dissolution of solid dispersions

摘要

Background: Maintaining a supersaturated drug solution after the dissolution of the solid dispersions of water insoluble drugs continues to be a great challenge and is important to the oral bioavailability enhancement of hardly soluble drugs. Methods: Nimodipine solid dispersions were prepared by hot-melt extrusion and a special tri-block polymer was employed as a co-carrier. The solid dispersions were characterized by modulated differential scanning calorimetry, transmission electron microscopy, hydrogen-nuclear magnetic resonance and so on. Results: The tri-block polymer was able to inhibit the formation of drug crystals after dissolution of the solid dispersions. Due to the unique interfacial layer formation ability of the tri-block polymer, a special drug loading micelle which encapsulated the compound and the hydrophobic fragments of the copolymers appeared in the release media. The tri-block polymer was composed of a hydrophilic part forming the shell of micelles, a hydrophobic part shaping the core of micelles, and a special intermediate hydrophilicity part constructing the interfacial layer of micelles. Conclusion: The tri-block polymer was not only able to stabilize the supersaturated drug solution of solid dispersions to enhance the oral bioavailability of hardly soluble drugs, but is also a potential candidate to construct micelles for systemic administration, due to the good compatibility and organic solvents free micelle formation procedure.