The Combined Use of Imaging Approaches to Assess Drug Release from Multicomponent Solid Dispersions

Pharm Res. 2017 May;34(5):990-1001. doi: 10.1007/s11095-016-2018-x. Epub 2016 Aug 29.

Abstract

Purpose: Imaging methods were used as tools to provide an understanding of phenomena that occur during dissolution experiments, and ultimately to select the best ratio of two polymers in a matrix in terms of enhancement of the dissolution rate and prevention of crystallization during dissolution.

Methods: Magnetic resonance imaging, ATR-FTIR spectroscopic imaging and Raman mapping have been used to study the release mechanism of a poorly water soluble drug, aprepitant, from multicomponent amorphous solid dispersions. Solid dispersions were prepared based on the combination of two selected polymers - Soluplus, as a solubilizer, and PVP, as a dissolution enhancer. Formulations were prepared in a ratio of Soluplus:PVP 1:10, 1:5, 1:3, and 1:1, in order to obtain favorable properties of the polymer carrier.

Results: The crystallization of aprepitant during dissolution has occurred to a varying degree in the polymer ratios 1:10, 1:5, and 1:3, but the increasing presence of Soluplus in the formulation delayed the onset of crystallization. The Soluplus:PVP 1:1 solid dispersion proved to be the best matrix studied, combining the abilities of both polymers in a synergistic manner.

Conclusions: Aprepitant dissolution rate has been significantly enhanced. This study highlights the benefits of combining imaging methods in order to understand the release process.

Keywords: FT-IR spectroscopic imaging; amorphous solid dispersion; confocal Raman spectroscopy; crystallisation; magnetic resonance imaging.

MeSH terms

  • Aprepitant
  • Chemistry, Pharmaceutical / methods
  • Crystallization
  • Drug Carriers / chemistry
  • Drug Liberation
  • Magnetic Resonance Imaging / methods
  • Morpholines / chemistry*
  • Polyethylene Glycols / chemistry*
  • Polymers / chemistry*
  • Polyvinyls / chemistry*
  • Pyrrolidines / chemistry*
  • Solubility
  • Spectroscopy, Fourier Transform Infrared / methods
  • Water / chemistry

Substances

  • Drug Carriers
  • Morpholines
  • Polymers
  • Polyvinyls
  • Pyrrolidines
  • poly(N-vinylpyrrolidine)
  • polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
  • Water
  • Aprepitant
  • Polyethylene Glycols