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Keywords:

  • solid-state NMR;
  • formulation;
  • amorphous;
  • solid solutions;
  • relaxation time;
  • solid dosage form;
  • electrospinning;
  • extrusion

Abstract

A major focus area in improving pharmaceutical manufacturing is decreasing powder-handling steps such as milling, granulation, and blending. One approach to go directly from active pharmaceutical ingredients (API) and excipients in solution to a formulated drug product is to use electrospinning to make solid formulations of API in a polymer. Because of the rapid evaporation rate in electrospinning, the process usually results in a well-mixed solid dispersion of drugs in the polymer. In this study, solid-state nuclear magnetic resonance is used to examine phase separation in formulations of aliskiren (SPP) and indomethacin (IND) with polyvinylpyrrolidone (PVP) prepared by electrospinning and hot-melt extrusion. It was found that 1:1 SPP–PVP, 1:1 IND–PVP, and 4:1 SPP–PVP formulations prepared by electrospinning are homogeneous solid solutions down to a 2–11 nm length scale, whereas a 4:1 SPP–PVP formulation prepared by hot-melt extrusion exhibits phase separation with domain sizes of 20–100 nm or larger. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1538–1545, 2012