Investigation of Solid Dosage Form Components Interaction Using Orthogonal Techniques- Discovery of New Forms of Sodium Stearyl Fumarate

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in under accelerated storage conditions. Due to the complex matrix (including API, polymer, fillers, super disintegrant lubricant), it challenging pinpoint component(s) responsible for peak. addition PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) Infrared (IR) spectroscopy were employed investigation understand root cause mechanistically. Specifically, multi nuclei SSNMR (1H, 23Na, 13C) instrumental delineating of matrix. We identified be an acid base reaction occurring DP, whereby sodium ion stearyl fumarate (SSF) is replaced by proton leading SSF form conversion. also commercially available hydrate that dehydrate anhydrous heating. general, same used investigate any component solid dosage forms.