The hydration behavior of an amphiphilic excipient, Gelucire 44/14, has been investigated. Two types of hydration processes were studied: one with increasing humidity to investigate the conditions during storage, and one with increasing water contents to study the behavior during dissolution. In addition, the main components of the excipient were investigated separately. These were polyethylene glycol (PEG), PEG monolaurate and PEG dilaurate (PEG esters), trilaurin (glyceride) and glycerol. The water uptake of Gelucire 44/14 at humidity ratios less than 60%RH was very low (about 1 wt%), which was attributed to the dissolution of the most hydrophilic component, glycerol. The water uptake increased substantially above 70%RH as PEG started to dissolve, followed by the PEG esters. It was concluded that each component equilibrates separately with the aqueous solution, which itself is in equilibrium with the humid air. Hence, a liquid phase can form between the crystals with a chemical potential decided by the humidity ratio. The water uptake of Gelucire 44/14 could be described as a sum of the uptake of the individual components, weighted according to their relative amounts in the mixture. Phase maps of the Gelucire 44/14 and its components at different water contents were constructed. Dry Gelucire 44/14 contains lamellar crystals of mainly PEG and PEG esters which melt at 44 ºC. The crystals do not swell at increasing humidity, but dissolve above 75%RH at a water content of 5 wt% in the excipient. At increasing water contents Gelucire 44/14 forms white gels composed of hexagonal and lamellar mesophases dispersed in a continuous liquid phase. These liquid crystalline phases dissolve at 35 ºC, i.e. below physiological temperatures. A dramatic viscosity maximum was observed in the lamellar region at 50 wt% water, which may be attributed to the formation of networks of PEG esters. The pure PEG esters were found to form cubic mesophases at 50 wt% water. The instruments used in this study were Dynamic Vapor Sorption (DVS), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Small- and Wide Angle X-ray Scattering (SWAXS) and Optical Microscopy
