Molecular phenomena related to moisture uptake in amorphous solid dispersion loaded with bosentan monohydrate and copovidone

Abstract

Amorphous bosentan alone lacks dissolution flux that could enhance its bioavailability. Its coamorphization with hydrophilic copovidone (1:1) enables to improve wettability and dissolution rate, but fine amorphous particles are prone to moisture uptake. Water sorbed on the surface of this amorphous solid dispersion can considerably alter its physical properties annihilating benefits of coamorphization. The gravimetric measurements of water uptake, the solid state 1H NMR spectroscopy and relaxometry enabled us to describe for the first time, phase changes initiated by hydration in amorphous bosentan systems. The properties of copovidone greatly impacted water uptake in bosentan solid dispersions. A nonlinear reduction of the Tg upon water sorption resulted in the transformation of the glassy state into the rubbery state at ambient temperature. The state diagrams were developed for optimization of manufacturing conditions, selection of suitable packaging material and storage temperature, ensuring long-term stability of amorphous bosentan products.