Evaluation Of Self-Emulsifying Drug Delivery Systems For Oral Insulin Delivery Using An In Vitro Model Simulating The Intestinal Proteolysis

The gentle preparation and the functionalization potential of self-emulsifying drug delivery systems (SEDDS) make them an interesting formulation strategy for oral administration of peptide and protein (p/p) drugs.

A series of Kolliphor® RH40 (RH40) and Labrasol® (LAB) glycerides-based SEDDS containing either long-chain (LC) or medium-chain (MC) were formulated and characterized with regard to their rheological behavior, as well as the size distribution and zeta potential of formed emulsions. Insulin, in order to be incorporated in SEDDS, was complexed with soybean phosphatidylcholine before loading. The ability of different SEDDS to protect incorporated insulin against enzymatic hydrolysis was evaluated by an in vitro model simulating the intestinal proteolysis. SEDDS were incubated in simulated intestinal fluids in the presence of α-Chymotrypsin, and HPLC was used to quantify the remaining insulin. Principal component analysis (PCA) was applied to identify the relations between different excipients and properties of SEDDS that describe SEDDS protective effect on insulin during proteolysis.

The RH40-SEDDS behaved Newtonian in the presence of ethanol (EtOH) and non-Newtonian when EtOH is absent, which generated emulsion with droplets between 30 to 300 nm. The LAB-SEDDS always behaved Newtonian and generated polydisperse emulsions with broad size distribution (190-4000 nm). During the vitro proteolysis, insulin can be effectively protected against proteolysis (e.g. > 60% remaining insulin after 60 min proteolysis). According to PCA analysis, insulin was better protected in MC-SEDDS compared to LC-SEDDS, and better in LAB-SEDDS compared to RH40-SEDDS. Monoacyl phosphatidylcholine and Capmul® MCM C8 were recognized as excipients favored for SEDDS protection on insulin. However, viscosity and the addition of EtOH played insignificant roles in the percentage of remaining insulin after proteolysis.

In summary, an in vitro proteolysis model with increased physiological relevance was applied to enable the optimal design of SEDDS for oral p/p drug delivery. More on SEDDS for oral insulin delivery