Chemical stability of phospholipid-stabilized supercooled smectic cholesteryl myristate nanoparticles

Abstract

Supercooled smectic cholesteryl myristate nanoparticle dispersions, a potential carrier system for lipophilic drugs, can be stabilized with phospholipids and their mixtures with sodium glycocholate. Such dispersions are commonly prepared by high-pressure melt homogenization. As cholesterol esters and phospholipids are both susceptible to oxidation and hydrolysis, the chemical stability of the dispersions was studied directly after preparation and during storage. Despite the high temperatures occurring during processing, no hydrolysis was detected in the dispersions directly after preparation. During storage for 5–8months, dispersions solely stabilized with phospholipids exhibited massive phospholipid hydrolysis as determined by HPTLC. Phospholipid hydrolysis resulted in distinct changes of the physicochemical properties such as pH, zeta potential, and phase behavior of the dispersions. In systems additionally containing sodium glycocholate as stabilizer, hydrolytic degradation occurred only to a minor extent. Phospholipid hydrolysis could also be reduced by adding TRIS- or phosphate-buffer (10mM, pH 7.4) to the aqueous phase before the preparation process. The addition of EDTA and α-tocopherol, which were mainly employed with the aim to suppress oxidation processes, also reduced the phospholipid hydrolysis to a certain extent. A partial oxidation of the cholesteryl myristate was observed in several dispersions by HPTLC, HPLC and mass spectrometry after long-term storage, but could be reduced by adding EDTA or α-tocopherol.