Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs

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.

New Preparation Method Using Microwave, Kinetics, In Vitro Dissolution‐Diffusion, and Anti‐Inflammatory Study of Diclofenac‐ Proline Co–Crystal

“…Poor homogeneity and low purity are two primary obstacles faced in the development of co‐crystal production. Usually, starting materials are still found in the resulting co‐crystal product, corresponding to low yield . Some methods have been reported to address these issues, including neat grinding, liquid‐assisted grinding, hot extrusion, and slow evaporation, all of which have specific advantages and disadvantages .…”

“…Usually, starting materials are still found in the resulting co-crystal product, corresponding to low yield. [1][2][3] Some methods have been reported to address these issues, including neat grinding, liquid-assisted grinding, hot extrusion, and slow evaporation, all of which have specific advantages and disadvantages. [4][5][6][7] Mechanochemical processes such as grinding, with or without solvents, is laborious in terms of maintaining the continuity due to particle size, surface property changes, and the electrostatic effect during the process.…”

Application of 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide as Coformer in Formation of Pharmaceutical Cocrystals

“…In the pharmaceutical sciences, the correct choice of a coformer for a desired API is essential [12]. The library of available coformers which fulfill structural prerequisites is significant; however, only selected compounds can be considered to belong to the group of "pharmaceutically useful" ones [13][14][15]. The basic requirement for a suitable coformer is to be pharmaceutically acceptable, i.e., generally regarded as safe (GRAS) substances.…”

21st century developments in the understanding and control of molecular solids

“…17 There are now a number of FDA approved co-crystal drug products including Entresto® (sacubitril-valsartan), Lexapro® (escitalopram oxalate), and Depakote® (valproate sodium cocrystal with valproic acid). 18 A particularly interesting recent result is the development of drug-drug cocrystals such as the 1:1 cocrystal of tramadol and celecoxib. 19 Amorphous materials and techniques used to study their local structure such as solid-state NMR spectroscopy 18 and total scattering techniques 20 have also seen considerable interest.…”

“…18 A particularly interesting recent result is the development of drug-drug cocrystals such as the 1:1 cocrystal of tramadol and celecoxib. 19 Amorphous materials and techniques used to study their local structure such as solid-state NMR spectroscopy 18 and total scattering techniques 20 have also seen considerable interest. The caveat is that amorphous materials are less thermodynamically stable than crystals and hence there is a need to find ways to stabilise them, particularly in the presence of moisture.…”