Prescription Design of Sinomenine Gel Based on Molecular Dynamics Simulations.

Sinomenine (SIN) is a drug for the treatment of rheumatoid arthritis, most of which is administered orally, but it is prone to adverse gastrointestinal effects. Gel can overcome the gastrointestinal adverse effects caused by oral administration. In this paper, a multiscale computational pharmaceutics strategy was developed to guide the systematic study of formulation factors of a SIN gel and, further, to guide the formulation design. A molecular dynamics (MD) simulations method was utilized to successfully screen the optimal prescription of SIN gel and to elucidate the molecular mechanisms affecting the quality of SIN gel. The optimal prescription was 3.0% of SIN, 1.0% of Carbopol (Cp), 30% of Ethanol (Eth), 5.0% of Glycerine (Gly) and 10.0% of Menthol (Men). The influence mechanism can be explained by the combination of multiple parameters, such as the microstructure diagram, the radius of gyration (Rg) and the radial distribution function (RDF). In vitro transdermal studies were carried out using a modified Franz diffusion cell method to evaluate the quality of the screened and reference prescriptions. The results showed that the cumulative penetration and penetration rate of the screening of prescription were better than the reference formulation. Most important of all, the simulation results are in good agreement with the in vitro release experiment, indicating that the strategy has good applicability. This study was able to accurately optimize the formulation and elucidate the molecular mechanism, which would provide a reference for further research on SIN and gel.