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

Abstract

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.

Effect of Oral Administration of Polyethylene Glycol 400 on Gut Microbiota Composition and Diet-Induced Obesity in Mice

“…Therefore, we hypothesized that PEG administration could affect the metabolic phenotype by altering the composition of the gut microbiota. Accordingly, we examined the effect of PEG400 on the gut microbiota and diet-induced obesity in mice fed a HFD, given that PEG400, but not PEG4000, is used as a dispersant for potential drugs against metabolic diseases, such as hyperlipidemia, in animal experiments [ 27 ]. Consistent with the gut microbiota composition of PEG-administered ND-fed mice, administering a high concentration of PEG400 reduced the number of species observed in HFD-fed mice ( Figure 2 A).…”

Integrating Artificial Intelligence for Drug Discovery in the Context of Revolutionizing Drug Delivery

“…GastroPlus [134] is a platform that utilizes AI and predictive modeling to aid in the design and optimization of drug formulations. This software is used for pharmaceutical products (dosage form) in many animal models, including rats, primates, and animals, allowing researchers to predict the drug absorption, distribution, metabolism, and excre-tion [135]. GastroPlus's AI-driven approach aids in the development of more effective and bioavailable drug formulations, streamlining the drug development process.…”