Storage Stability of Bivalirudin: Hydrophilic Versus Lipophilic Solutions

It was the aim of this study to incorporate a model peptide bivalirudin in self-emulsifying drug delivery system (SEDDS) and compare its storage stability with conventional aqueous solutions. Firstly, bivalirudin lipophilicity was increased via hydrophobic ion pairing using anionic or cationic surfactants. The chosen bivalirudin docusate complex (BIV/AOT) was incorporated into SEDDS composed of 40% (w/w) Cremophor EL, 20% (w/w) Capmul PG-8, and 40% (w/w) propylene glycol with a drug payload of 0.20% (w/w). SEDDS were stable over a wide pH range for at least 7 days at 37°C and showed an immediate bivalirudin release profile. Moreover, aqueous bivalirudin solutions were shown to be most stable between apparent pH 3 and 4. Furthermore, 94.39% and 72.66% of bivalirudin in SEDDS and 10% propylene glycol, respectively, remained intact after 90 days of storage at 25°C ± 2°C, whereas 99.12% and 80.54% were still intact in SEDDS and 10% propylene glycol at 5°C ± 3°C, respectively. Bivalirudin in reconstituted commercially available product Angiomax® was, however, long-term unstable. According to these findings, SEDDS could be considered as a potential bivalirudin stabilization medium against chemical degradation.