Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design.
As small molecule drugs become harder to develop and less cost effective for patient use, efficient strategies for their property improvement become increasingly important to global health initiatives. Improvements in the physical properties of Active Pharmaceutical Ingredients (APIs), without changes in the covalent chemistry, have long been possible through the application of binary component solids. This was first achieved through the use of pharmaceutical salts, within the last 10-15years with cocrystals and more recently coamorphous systems have also been consciously applied to this problem. In order to rationally discover the best multicomponent phase for drug development, intermolecular interactions need to be considered at all stages of the process. This review highlights the current thinking in this area and the state of the art in: pharmaceutical multicomponent phase design, the intermolecular interactions in these phases, the implications of these interactions on the material properties and the pharmacokinetics in a patient.
Durham University, Division of Pharmacy, Queen's Campus, Stockton on Tees, TS17 6BH, UK. Electronic address: d.j.berry@durham.ac.uk.
David J
DJ
Berry
Department of Chemistry, Durham University, University Science Laboratories, South Road, Durham, DH1 3LE, UK.
Jonathan W
JW
Steed
D003460:Crystallization; D015195:Drug Design; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012492:Salts
D004364:Pharmaceutical Preparations; D012492:Salts
Bioavailability; Cocrystal; Intermolecular interactions; Pharmaceutical; Pharmacokinetics; Physicochemical properties; Salt; multicomponent crystals