Solid-state NMR characterization of high-loading solid solutions of API and excipients formed by electrospinning.
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.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Blair
B
Brettmann
Erin
E
Bell
Allan
A
Myerson
Bernhardt
B
Trout
D000577:Amides / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005079:Excipients / Q000008:administration & dosage*; D005650:Fumarates / Q000008:administration & dosage*; D007213:Indomethacin / Q000008:administration & dosage*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011205:Povidone / Q000008:administration & dosage; D012996:Solutions
D000577:Amides; D005079:Excipients; D005650:Fumarates; D012996:Solutions; C446481:aliskiren; D011205:Povidone; D007213:Indomethacin