23rd Annual Conference of the German Crystallographic Society, March 16-19, 2015, Göttingen, Germany

Trapping liquid drugs inside crystals

A. Bacchi 1

University of Parma , Dipartimento di Chimica, Parma, Italy

The objective of this work is to find a systematic way to embed liquid or volatile molecules inside crystalline materials, with the multiple aims of stabilizing them, of tuning their possible ways of delivery in medicine or agrochemistry, and to explore new regulatory and intellectual properties issues. Liquid or volatile formulations of active pharmaceutical ingredients (APIs) are intrinsically less stable and durable than solid forms; in fact most drugs are formulated as solid dosage because they tend to be stable, reproducible, and amenable to purification. Most drugs and agrochemicals are manufactured and distributed as crystalline materials, and their action involves the delivery of the active molecule by a solubilization process either in the body or on the environment. The poor solubility of pharmaceutical active ingredients (API) or the reverse too high solubility of agrochemicals are problems often encountered in their formulation since these phenomena limit respectively the bioavailability of the API or the duration of the action of the agrochemical. However some important compounds for the human health or for the environment occur as liquids at room temperature. We have defined a benchmark of molecules relevant to human health and environment that have been combined with suitable partners according to the well known methods of crystal engineering in order to embed them in crystalline hosts. Our approach is twofoled, by using cocrystals and MOFs.

The formation of co-crystals has been demonstrated as a means of tuning solubility properties of solid phases, and therefore it is widely investigated by companies and by solid state scientists especially in the fields of pharmaceuticals, agrochemicals, pigments, dyestuffs, foods, and explosives. In spite of this extremely high interest towards co-crystallization as a tool to alter solubility, practically no emphasis has been paid to using it as a means to stabilize volatile or labile or liquid products. In this work we trap and stabilize volatile and liquid APIs and agrochemicals in crystalline matrices by engineering suitable co-crystals. These new materials alter the physic state of the active ingredients allowing to expand the phase space accessible to manufacturing and delivery. We also explore the possibility to include liquid APIs inside the pores of suitable designed MOFs, again with the aim of stabilizing their solid state formulation.