Elucidation of the Controlled Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum-Chitosan Polymers: Computational and Experimental Studies

The development and evaluation of a controlled-release (CR) solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS) and metoprolol succinate (MS) is reported. The research is, partly, based upon the utilization of computational tools; in this case molecular dynamics simulations (MDs) and response surface method (RSM), in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and XG) to drug ratio (P:D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG:LCS as well as XG and high molecular weight CS, showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favourable complex is formed when LCS is used at 15 % (w/w) and, importantly, that the interaction between XG and LCS is more favoura...