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

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.