Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design

Abstract

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.

Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers

“…If at least one of the components is an active pharmaceutical ingredient (API) and if the coformer is pharmaceutically acceptable, then the substance is recognized as pharmaceutical cocrystal. A pharmaceutical cocrystal can offer multiple benefits for physicochemical and biopharmaceutical properties of APIs, such as increased solubility and dissolution rates, improvement of mechanical properties, and stability [13][14][15]. Particularly, cocrystals have exhibited higher, similar or lower solubility compared to the parent API, depending on the nature of the coformer and the solution conditions [16,17].…”

Achieving Balanced Energetics through Cocrystallization

“…ADN has failed to see wide‐spread implementation due to issues with processing, hygroscopicity, and thermal stability . As cocrystallization has proved effective at modulating bulk materials properties in various fields including drug delivery, non‐linear optics, organic electronics, and EMs this presents a promising route to balanced EMs while concomitantly redressing ADNs undesirable properties. However, whereas cocrystallization is now widely studied, cocrystallization between neutral and ionic coformers has yet to significantly impact areas outside of pharmaceuticals .…”

Achieving Balanced Energetics through Cocrystallization

“…As cocrystallization has proved effective at modulating bulk materials properties in various fields including drug delivery, non‐linear optics, organic electronics, and EMs this presents a promising route to balanced EMs while concomitantly redressing ADNs undesirable properties. However, whereas cocrystallization is now widely studied, cocrystallization between neutral and ionic coformers has yet to significantly impact areas outside of pharmaceuticals . This may be due to the difficulties in a priori cocrystal design or the added influence of strong coulombic forces arising from ion–ion interactions.…”

“…[3] ADN has failed to see wide-spread implementation due to issues with processing, hygroscopicity,a nd thermal stability. [4] As cocrystallization has proved effective at modulating bulk materials properties in various fields includ-ing drug delivery, [5] non-linear optics, [6] organic electronics, [7] and EMs [8] this presents ap romising route to balanced EMs while concomitantly redressing ADNs undesirable properties. However,w hereas cocrystallization is now widely studied, cocrystallization between neutral and ionic coformers has yet to significantly impact areas outside of pharmaceuticals.…”

“…However,w hereas cocrystallization is now widely studied, cocrystallization between neutral and ionic coformers has yet to significantly impact areas outside of pharmaceuticals. [5] This may be due to the difficulties in ap riori cocrystal design or the added influence of strong coulombic forces arising from ion-ion interactions.T hese issues are compounded in EMs by the general lack of supramolecular synthons typically employed in cocrystal design. [9] Few examples exist outside of energetic salt:crown ether complexes [10] and the very recent report of an hexanitrohexaazaisowurtzitane (CL-20):1-amino-3-methyl-1,2,3-triazolium nitrate cocrystal.…”