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

Publication: ACS Omega
Software: GastroPlus®


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 x1 = 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 (δx1,3 = 1.65 × 10–2) for RST by PEG400 was attained at x1 = 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.

By Afzal Hussain, Obaid Afzal, Sabina Yasmin, Nazima Haider, Abdulmalik Saleh Alfawaz Altamimi, Fleming Martinez, William E. Acree Jr., and Mohhammad Ramzan