Abstract
Cocrystals can be used as an alternative approach based on crystal engineering to enhance specific physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs) when the approaches to salt or polymorph formation do not meet the expected targets. In this article, an overview of pharmaceutical cocrystals will be presented, with an emphasis on the intermolecular interactions in cocrystals and the methods for their preparation. Furthermore, cocrystals of direct pharmaceutical interest, along with their in vitro properties and available in vivo data and characterization techniques are discussed, highlighting the potential of cocrystals as an attractive route for drug development.
Highlights
When determining the physical form in which active pharmaceutical ingredients (APIs) will be administered, the optimization of properties including solubility, dissolution rate, mechanical properties, hygroscopicity, physical stability and chemical stability is of strategic importance
The high degree of interest in cocrystals is obvious from the increasing numbers of publications, applications for patents, and their recent introduction in the Cambridge Structural Database (CSD), which is an essential tool in the field of crystal engineering
Computational predictions of cocrystal formation have been carried out by measuring the lattice energy under the crystal structure prediction (CSP), to confirm whether cocrystals are thermodynamically more stable than the pure crystals of the substances [39]. Another approach is based on the measurement of molecular electrostatic potential surfaces (MEPS) to assess molecular complementarity, as well as the possibility of forming cocrystals based on an electrostatic model that recognizes intramolecular interactions as a contact point between specific interaction points on the molecular surfaces [40]
Summary
When determining the physical form in which active pharmaceutical ingredients (APIs) will be administered, the optimization of properties including solubility, dissolution rate, mechanical properties, hygroscopicity, physical stability and chemical stability is of strategic importance. A cocrystal is a crystalline entity-complex formed by two (or more) different, distinct molecular entities/ingredients, which are solid at ambient temperatures, and within which the intermolecular interactions in the unique crystal lattice generated are weak forces (non-covalent and non-ionic), such as hydrogen bonds, π bonds and van der Waals bonds. At this point, it should be mentioned that there is considerable debate surrounding the definition of cocrystal. The final section of this review covers, in brief, techniques for the characterization of cocrystals, especially those that are routinely used in drug delivery and development laboratories
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