Water vapour sorption in tadalafil-Soluplus co-milled amorphous solid dispersions

Abstract This study focuses on the impact of hygroscopic polymer (Soluplus) on the physical stability of amorphous solid dispersions of tadalafil (TD) prepared by high-energy ball milling. X-ray powder diffraction, hydration kinetics, 1 H solid state NMR ( 1 H ssNMR) and 1 H relaxometry are used to assess the physical features of model solid dispersions, containing 50 (0.5TD) or 90 (0.1TD) wt.% of the polymer, after their exposition to the relative humidity (RH), ranging from 11 to 100%. For reasons of comparison, neat TD and polymer alone were also analysed. Three water fractions, namely: loosely, tightly, and very tightly bound water were identified on the basis of hydration curses, and a multilayer moisture sorption model was proposed. An increase in Soluplus loading led to two times higher saturation hydration levels. Despite the presence of tightly bound water in the system, 1 H ssNMR spectra revealed that the matrix of solid dispersion did not dissolve in the absorbed water vapour even at elevated air humidity. However, after one week storage in open container at 76% of RH, the weight of solid dispersion 0.5TD increased of about 7%, and diffraction pattern showed starting recrystallization of the amorphous TD. Thus, a package of high barrier to water vapour should be recommended for these formulations.