Experimental screening and molecular dynamics simulation study on wetting agent in dry suspension

Abstract

Suspension is the common preparation whose absorption rate is second only to the solution. However, problems like the difficulty in screening excipients and the complicated screening process limit its application to a certain extent. In this study, trimethoprim (TMP) was used as the research object. Compound sulfachlorpyridazine sodium Powder(CSSP) containing TMP was used as the research vector to explore the effects of wetting agent(WA), mixing processes between excipients and drug on the preparation stability from the perspectives of the change of the surface free energy between the drug powder and solvent, the reduction of the particle size of the drug, and the interaction between the drug and the excipients, serving the contact angle, sedimentation volume ratio, re-dispersibility, particle size, and appearance as indicators. In addition to that, taking the number density distribution, mean square displacement (MSD), and van der Waals force (VDW) as indicators, the molecular dynamics (MD) simulation technique was employed to explore the differences in the wetting ability of wetting agents (WAs) and the wetting mechanism of WAs on drug molecules. Suitable indicators were screened to provide new ideas for the initial screening of wetting agents from the simulation level and other solutions in tedious and time-consuming problems of experimental excipients screening.