Formulation design and mechanism study of hydrogel based on computational pharmaceutics theories

Formulation design and mechanism study of the drug delivery system (DDS) is an important but difficult subject in pharmaceutical research. The study of formulation factors is the most time- and labor-consuming work of formulation design. In this paper, a multiscale computational pharmaceutics strategy was developed to guide the systematic study of formulation factors of a typical polymer-based DDS, hydrogel, and further to guide the formulation design. According to the strategy, the combination of solubility parameter (δ) and diffusion coefficient (D) calculated by the AA-MD simulation was suggested as the general evaluation method for the matrix screening of the hydrogels at the pre-formulation stage. At the formulation design stage, the CG-MD simulation method was suggested to predict the morphology and drug-releasing behavior of the hydrogels under different formulation factors. The influence mechanism can be explained by the combination of multiple parameters, such as the microstructure diagram, the radius of gyration (Rg), the radial distribution function (RDF), and the free diffusion volume (V_diffusion). The simulation results are in good agreement with the in vitro release experiment, indicating that the strategy has good applicability.