Four solidification methods for self-emulsifying drug delivery systems (SEDDS) were compared to evaluate the impact of solidification on storage stability of an incorporated protein. Papain was loaded in SEDDS via hydrophobic ion pairing (HIP). Liquid SEDDS (l-SEDDS) were either solidified by adsorption to solid excipients such as magnesium-aluminometasilicate via wet granulation (s(silica)-SEDDS) and carbohydrates via lyophilisation (s(carbo)-SEDDS) or by incorporation of high-melting PEG-surfactants (s(PEG)-SEDDS) and triglycerides (s(oil)-SEDDS) in SEDDS preconcentrates. Land s-SEDDS were compared regarding intrinsic emulsion properties, solid-state form of papain, enzyme stability and activity during storage. HIP with deoxycholate showed a precipitation efficiency of 82% and papain maintained 90% of its initial activity. Incorporated papain was present in an amorphous state, confirming a molecular dispersion in all preconcentrates. In comparison to l-SEDDS each solidification method investigated improved the storage stability of incorporated papain. Neither precipitation nor phase separation was observed for s-SEDDS. s(PEG)-SEDDS demonstrated with 87.8% the highest enzymatic activity and displayed according to the following rank order: s(PEG)-SEDDS > s(oil)-SEDDS > s(silica)-SEDDS > s(carbo)-SEDDS > l-SEDDS the highest remaining papain activity after 30 days of storage. This work clearly demonstrates that solidified SEDDS can provide a significantly improved storage stability for therapeutic proteins compared to corresponding liquid formulations. (C)2020 The Authors. Published by Elsevier Inc.