Synthon competition in new pharmaceutical forms: how crystal structure affects properties
M. Teresa Duarte, Vânia André, Fabrizia Grepioni, Naír Rodríguez‐Hornedo, Chinmay Maheshwari · Acta Crystallographica Section A Foundations of Crystallography · 2011
Crystal design and engineering has received much attention in recent years as its implications extend to material science, solid state reactions and synthesis, and drug development.One of the most important issues in this field is the rational design and arrangement of molecular packing, which affects and controls the macroscopic properties of materials.A comprehensive understanding of supramolecular systems is primarily dependent on the knowledge of intermolecular interactions controlling the molecular aggregation, with major emphasis on hydrogen and halogen bonding as well as aromatic stacking.Synthon formation and breaking is a main key and the driving force in structure-properties relationships.More significant than knowing the structure of new API forms is to correlate that information with the properties of the novel compounds.Stability and solubility are major factor known to strongly affect API's performance and therefore their correlation with structural and thermal data is of upmost importance.As an example several cocrystals and molecular salts of gabapentinlactam (GBPL), a prodrug with proven neuroleptic effects, were unveiled and fully characterized; the pH-dependent solubility of these novel forms were studied and a correlation between solubility data, structural information and thermal stability has been purposed.Studies with gabapentin (GBP), a neuroleptic drug, yielded several multicomponent crystal forms whose thermal and pH stability have also been determined With the antibiotic 4-aminosalicylic acid (4ASA) eleven new crystal forms were disclosed, including polymorphs, solvates, cocrystals, molecular salts and salts.A novel hydrated form of the antihypertensive perindopril erbumine was found, the first molecular structures of this API were determined, and the relative stability compared to the commercial forms were studied [1] V.