BACKGROUND: The present manuscript highlights the material pursuits of selected antioxidants i.e., gentisic acid and L-tyrosine by exploring their various polymorphic modifications using virtual and experimental approach.
METHODS: Polymorph Prediction/Crystal structure prediction (CSP) was undertaken using Polymorph Predictor module of BIOVIA Material Studio software. The lattice energy landscape representing various low energy and high density polymorphic forms was generated. Simultaneously various solid forms were experimentally isolated from different solvents/or solvent mixtures. Their characterization using various analytical tools was done. Crystal structure determination was carried out using Reflux Plus module of BIOVIA Material Studio software. Lattice energy landscape was scanned to hunt for these observed forms. Crystal morphology study was performed to ascertain morphologically important (M.I.) facets. The solubility behavior and intrinsic dissolution rate of these forms were then determined to evaluate their behavior in solution form. Besides this, in vivo (animal) studies based on the behavioral patterns were performed to check their clinical relevance.
RESULTS: Four polymorphs (including the form present in commercial sample), one solvatomorph of gentisic acid, three forms of L-tyrosine (including the form present in commercial sample), and one solvatomorph of L-tyrosine were obtained from various solvents/or solvent mixtures. It was noticed that these experimentally isolated forms were present as local minima in the lattice energy landscape of predicted structures of the respective drug molecules. It was observed that form III each of gentisic acid and L-tyrosine was found out to be most soluble amongst other forms of these antioxidants. The animal studies reflecting behavioral changes further supported the clinical effectiveness of form II and III of gentisic acid and form III of L-tyrosine.
CONCLUSION: This research work illustrates the relevance of CSP in studying the various polymorphic modifications of chosen drug moieties. Crystal structure determination from PXRD patterns is a reliable approach towards drug development process. The information generated from various material findings, in vitro and in vivo studies of selected antioxidants can be useful in the emerging field of anti-ageing therapy.
