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

Int J Nanomedicine. 2018 Mar 16:13:1611-1619. doi: 10.2147/IJN.S152415. eCollection 2018.

Abstract

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.

Keywords: disintegrate; micelles; recrystallization; solid dispersions; stability in blood circulation.

MeSH terms

  • Animals
  • Calorimetry, Differential Scanning
  • Caprolactam / analogs & derivatives
  • Caprolactam / chemistry
  • Drug Carriers / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Micelles
  • Pharmaceutical Preparations / chemistry*
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Povidone / chemistry
  • Proton Magnetic Resonance Spectroscopy
  • Rats
  • Solubility
  • Solutions
  • Solvents / chemistry
  • Vinyl Compounds / chemistry
  • Water / chemistry

Substances

  • Drug Carriers
  • Micelles
  • Pharmaceutical Preparations
  • Polymers
  • Solutions
  • Solvents
  • Vinyl Compounds
  • Water
  • poly-N-vinylcaprolactam
  • Polyethylene Glycols
  • Caprolactam
  • Povidone
  • vinyl acetate