Supersaturation in human gastric fluids

PurposeThe current study reports on supersaturation, precipitation and excipient mediated precipitation inhibition of five poorly soluble drugs (loviride, glibenclamide, itraconazole, danazol, and etravirine) in human and simulated gastric fluids.MethodUpon induction of supersaturation in human gastric fluids (HGFs), simulated gastric fluid (SGF), and fasted state simulated gastric fluid (FaSSGF) using a solvent shift method, supersaturation and precipitation were assessed as a function of time. In addition, the precipitation inhibitory capacity of three polymers (Eudragit® E PO, HPMC-E5, and PVP K25) was investigated.ResultsSupersaturation in human gastric fluids was observed for all model compounds, but proved to be relatively unstable (fast precipitation), except for itraconazole. Only modest excipient-mediated stabilizing effects on supersaturation were observed using HPMC-E5 and Eudragit® E PO whereas PVP K25 exerted no effect. In contrast to SGF, the observed precipitation behavior in FaSSGF was similar to the behavior in human gastric fluids.ConclusionThe present study demonstrates that supersaturation stability of drugs in human gastric fluids is in general inferior to supersaturation stability in intestinal fluids. As the potential for excipient mediated precipitation inhibition in gastric fluids was only limited, our data suggest that supersaturation should preferably be targeted to the intestine.

Graphical abstractHuman gastric fluids (HGFs) were aspirated from healthy voluteers. The supersaturation/precipitation behavior of five poorly soluble drugs and the precipitation inhibitory capacity of three polymers was investigated in human gastric fluid and, for comparative purposes, also in simulated gastric fluid (SGF) and fasted state simulated gastric fluid (FaSSGF).Figure optionsDownload full-size imageDownload high-quality image (112 K)Download as PowerPoint slide