Physico-chemical characterization of aspirated and simulated human gastric fluids to study their influence on the intrinsic dissolution rate of cinnarizine

To elucidate the critical parameters affecting drug dissolution in the human stomach, the intrinsic dissolution rate (IDR) of cinnarizine was determined in aspirated and simulated human gastric fluids (HGF). Fasted aspirated HGF (aspHGF) was collected from 23 healthy volunteers during a gastroscopic examination. Hydrochloric acid (HCl) pH 1.2, fasted state simulated gastric fluid (FaSSGF), and simulated human gastric fluid (simHGF) developed to have rheological, and physico-chemical properties similar to aspHGF, were used as simulated HGFs. The IDR of cinnarizine was significantly higher in HCl pH 1.2 (952 +/- 27 mu g/(cm2.min)) than in FaSSGF pH 1.6 (444 +/- 7 mu g/(cm2.min)), and simHGF pH 2.5 (49 +/- 5 mu g/(cm2.min)) due to the pH dependent drug solubility and viscosity differences of the three simulated HGFs. The shear thinning behavior of aspHGF had a significant impact on the IDR of cinnarizine, indicating that the use of FaSSGF, with viscosity similar to water, to evaluate gastric drug dissolution, might overestimate the IDR by a factor of 100-10.000, compared to the non-Newtonian, more viscous, fluids in the human stomach. The developed simHGF simulated the viscosity of the gastric fluids, as well as the IDR of the model drug, making it a very promising medium to study gastric drug dissolution in vitro.

Automated summary

This study investigated the critical parameters affecting drug dissolution in the human stomach by determining the intrinsic dissolution rate of cinnarizine in aspirated and simulated human gastric fluids. The results showed that the pH dependent drug solubility and viscosity differences of the simulated gastric fluids significantly influenced the dissolution rate of cinnarizine. Using a medium with viscosity similar to water to evaluate gastric drug dissolution may overestimate the dissolution rate. The developed simulated human gastric fluid showed promise in studying gastric drug dissolution in vitro.