Solid-state nuclear magnetic resonance study of the physical stability of electrospun drug and polymer solid solutions

J Pharm Sci. 2012 Jun;101(6):2185-93. doi: 10.1002/jps.23107. Epub 2012 Mar 12.

Abstract

A major challenge in utilizing the amorphous form of an active pharmaceutical ingredient (API) in a final oral dosage form is preventing crystallization over time and ensuring stability. One method to improve stability is lowering the mobility of an API by formulating as a solid solution with an excipient. In this work, we use electrospinning to prepare solid solutions of API, aliskiren (SPP) or indomethacin (IND), and a polymer, polyvinylpyrrolidone (PVP). The stability of the solid solutions over 6-month storage in a desiccator at 40 °C was investigated. Using X-ray diffraction and differential scanning calorimetry, it was determined that no crystals were present in the four formulations tested--1:1 SPP-PVP, 4:1 SPP-PVP, 1:1 IND-PVP, and 2:1 IND-PVP at any time. Solid-state nuclear magnetic resonance relaxation time measurements were used to determine whether phase separation of the API and polymer occurred during the study period. It was found that all formulations remained homogeneous down to at least a 2-10 nm length scale, indicating that for these APIs, electrospinning is an acceptable method for forming stable amorphous solid solutions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Drug Stability*
  • Magnetic Resonance Spectroscopy / methods*
  • Microscopy, Electron, Scanning
  • Polymers / chemistry*
  • X-Ray Diffraction

Substances

  • Polymers