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.

Highlights

Horse radish peroxidase (HRP) as a model protein was ion paired (HIP) with various ion pairing agents.

After HIP incorporation three liquid SEDDS were compared to three solid SEDDS formulations in terms of protein stabilization and preservation of its enzymatic activity during long-term storage.

Solid SEDDS were developed utilizing a solid oil base, which undergoes phase transition to liquid SEDDS at body temperature.

The activity of HRP in SEDDS formulations was found to be strongly 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, in contrast showed enhanced stability over 21 days of storage.

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

Materials

HRP, sodium lauryl sulfate, sodium docusate, Witepsol H32, H15, H35, E85, and W45 containing triglycerides,diglycerides and monoglycerides, Capmul MCM EP, Captex 355 and Lauroglycol FCC , Sodium pamoate, sodium decanoate, sodium myristate, sodium taurocholate, Solutol HS15, Kolliphor RH40, Kolliphor EL, Tween 80, Tween 40, Transcutol HP, DMSO, ethanol,  propylene glycol, Gelucire 44/14 (G44), Gelucire 48/16 (G48) and Gelucire 50/13 (G50).

Author links open overlay panelHaniyeh Etezadi, Aziz Maleki, Julian D. Friedl, AndreasBernkop-Schnürch
International Journal of Pharmaceutics
Available online 6 October 2020, 119918