Influence of drug physicochemical properties on absorption of water insoluble drug nanosuspensions

In order to investigate the influence of drug physicochemical properties on bioavailability of water insoluble drug nanosuspensions, five drug nanosuspensions were prepared using high pressure homogenization. These nanosuspensions were similar in particle size and same in stabilizer. Differential scanning calorimetry and powder X-ray diffraction analysis showed the crystalline state of the freeze dried nanocrystals did not change. In vitro dissolution test in fasted state simulated intestinal fluid (FaSSIF) and in vivo bioavailability study in rats demonstrated that the nanosuspensions had higher dissolution rate and higher AUC0–t and the ratios of dissolvednano/dissolvedmicro in 120 min were well correlated with the ratios of AUC0–t nano/AUC0–t micro. Correlation analysis between drug physicochemical properties and AUC0–t nano was performed and four-grid interpolation method was employed for interpolation and smooth surface fitting to give a visible trend. The results revealed that drug with smaller melting point, log P value around 5 and polar surface area value in the range of 50–60 would gain higher AUC0–t nano and accordingly better absorption of its nanosuspension. Melting point, log P and polar surface area were factors that influence the absorption of drug nanosuspensions in this study.

Figure optionsDownload high-quality image (204 K)Download as PowerPoint slide