Aprepitant Intravenous Emulsion Based on Ion Pairing/Phospholipid Complex for Improving Physical and Chemical Stability During Thermal Sterilization

Abstract

An aprepitant (APT) cholesteryl hemisuccinate (CHEMS) ion pair complex emulsion (AIPE) with high lecithin content was prepared to improve sterilization stability through the film dispersion homogenization method; therefore, it could be a promising delivery system of APT. Medium-chain triglycerides (MCT) was selected as the oil phase to improve the solubility and stability of APT in oil phase. DSC, XRD, FT-IR, and 1H-NMR spectroscopies confirmed that the APT-CHEMS ion pair (AIP) was formed between CHEMS and APT. The formation of AIP significantly increased the hydrophobicity of APT, allowing it to be completely embedded in the oil phase core to improve chemical stability and decrease hydrolysis of APT in the water phase. Also, CHEMS had a strong affinity with lecithin and could stabilize lipid membranes, forming a stronger and thicker interface membrane to increase the physical stability of AIPE. As a result, AIPE could withstand autoclaving at 120°C for 8 min without any change of particle size or content. Furthermore, AIPE with a potential of − 53.4 mV remained stable through spatial repulsion during sterilization. The encapsulation efficiency of AIPE was over 90% and the particle size was 106.8 ± 65.62 nm(0.286). Pharmacokinetic study in rats was comparable with that of CINVANTI which yielded a relative bioavailability of 114.31% indicating that the AIPE had similar pharmacokinetic processes in vivo with the analog of CINVANTI®. The AUC0–t of the AIPE was 4.31-fold that of the APT solution.