Storage stability of proteins in a liquid-based formulation: Liquid vs. solid self-emulsifying drug delivery

[Display omitted] •Horse radish peroxidase (HRP) as a model protein was ion paired (HIP).•Three liquid SEDDS were compared to three solid SEDDS formulations.•Solid SEDDS undergoing phase transition at body temperature were developed.•During storage protein stability and preservation of enzymatic activity was evaluated.•Activity of HRP in SEDDS formulations was found to be surfactant dependent.•Cremophor RH40 demonstrated improved stabilization of HRP in SEDDS.•After 48 h no HRP activity was detectable in liquid SEDDS.•HRP loaded in solid SEDDS showed enhanced stability over 21 days of storage. The objective of the present study was the development of self-emulsifying drug delivery systems (SEDDS) for oral delivery of therapeutic proteins providing storage stability. Horseradish peroxidase (HRP) serving as model protein was ion paired with docusate and incorporated into three liquid and three solid SEDDS formulations. Storage stability of HRP was determined over three weeks by quantifying its enzymatic activity. Generally, HRP maintained 78% of its initial enzymatic activity after complexation and loading into SEDDS. Having been incorporated in liquid SEDDS the protein showed limited stability and precipitated within a few hours. In contrast, in all solid SEDDS comprising of hard fats such as Witepsol W45 and solid surfactants such as Gelucire 44/14 and 48/16 as solidifying agents HRP was successfully stabilized. No decrease in HRP activity could be observed over the entire observation period. Solid SEDDS based on high-melting components can provide storage stability of incorporated proteins, whereas liquid SEDDS cannot.