Solid-state NMR characterization of high-loading solid solutions of API and excipients formed by electrospinning

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.