Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

by Selleckchem | May 12 2023

Rosuvastatin (RST) is a poorly water-soluble drug responsible for limited in vivo dissolution and subsequently low oral systemic absorption (poor bioavailability). The mole fraction solubility values of RST in various ratios of binary mixtures "{PEG400 (1) + water (2)}" at 298.15 K were employed to investigate the preferential solvation (PS) of RST (3) by the binary components. Moreover, the GastroPlus program predicted the drug dissolution/absorption rates, plasma drug concentration, and compartmental regional drug absorbed from a conventional tablet as compared to the RST-loaded (PEG400 + water) mixture (at x 1 = 0.5) in healthy subjects (considering the fast condition). Fedors' method was adopted to estimate the values of molar volume (314.8 cm3·mol-1) and Hildebrand solubility parameter (28.08 MPa1/2) of RST. The results of inverse Kirkwood-Buff integrals showed the PS of RST by PEG400 as observed in all studied ratios of the binary mixture. The highest PS value (δx 1,3 = 1.65 × 10-2) for RST by PEG400 was attained at x 1 = 0.5. Finally, the GastroPlus program predicted the maximum dissolution rate [20 mg within 15 min as compared to pure RST (1.5 mg within 15 min)]. Moreover, the program predicted increased in vivo oral absorption (1.2 μg/mL) and enhanced regional absorption (95.3%) of RST from upper segments of the gastrointestinal tract for the RST-loaded PEG400 + water mixture in humans as compared to conventional tablets (87.5% as total regional absorption and 0.88 μg/mL as in vivo absorption). Hence, the present binary system ferrying RST can be a promising strategy to control systemic dyslipidemia after oral or subcutaneous administration.

Comments：

The passage describes a study that investigates the solubility and preferential solvation (PS) of the poorly water-soluble drug, rosuvastatin (RST), in binary mixtures of PEG400 and water. The study also employs the GastroPlus program to predict the drug dissolution/absorption rates, plasma drug concentration, and compartmental regional drug absorption from a conventional tablet compared to RST-loaded PEG400 + water mixture in healthy subjects, considering the fast condition.

The study finds that RST has limited in vivo dissolution and low oral systemic absorption due to its poor bioavailability. The inverse Kirkwood-Buff integrals show that PEG400 is the preferred solvent for RST in all studied ratios of the binary mixture, with the highest PS value attained at x 1 = 0.5. The GastroPlus program predicts that the RST-loaded PEG400 + water mixture would result in a higher maximum dissolution rate, increased in vivo oral absorption, and enhanced regional absorption of RST from the upper gastrointestinal tract in humans as compared to conventional tablets.

The study concludes that the RST-loaded PEG400 + water mixture can be a promising strategy to control systemic dyslipidemia after oral or subcutaneous administration.