Physicochemical properties of an active pharmaceutical ingredient (API) depend on a chosen solid form within the structured drug product. These properties in turn affect pharmaceutical development and importantly the performance of the drug product in the clinic. Thus, solid-state modification of an API plays a significant role in the early stage of drug development. Various established options (e.g. amorphous form, polymorphs, salts [ionic complex], hydrates and solvates) are available for that purpose.

The ever increasing complexity with concomitant decrease in solubility of developmental API molecules makes the aforementioned options insufficient to produce viable solid forms for continued development. Co-crystallization is now recognized as an alternative and complementary approach for that purpose.

A co-crystal is a crystalline complex of two or more neutral molecular constituents bound together in the crystal lattice through non-covalent interactions, often via hydrogen bonding. In a pharmaceutical co-crystal one of the constituents is an API and the other component(s) is a pharmaceutically acceptable molecule (a pharmaceutical co-crystal former).

A co-crystal is a new form of an API and is patentable. Co-crystallization may potentially be employed with all APIs, including acidic, basic and non-ionizable molecules. In addition, the existence of a large number of potential co-crystal former increases the scope of pharmaceutical co-crystallization.

Thus, co-crystallization can find new solid forms to solve physicochemical properties (such as dissolution rate, stability, and mechanical properties) or to enable development of improved versions of existing drug products. 

Major challenges associated with pharmaceutical co-crystallization include: (1) the existence of a large number of potential co-formers which offers challenge to identify co-crystals and (2) large scale processing of co-crystals.

A wide range of methodologies for the co-crystal synthesis and screening are actively being developed. Of particular interest is sonication, which has significant potential for development as a high-throughput methodology.

In addition, sonication can provide an opportunity for large scale manufacturing of co-crystals and binary crystals. Indeed, Prosonix has been employing proprietary ultrasonic pharmaceutical particle engineering technologies in the manufacture of many high value pharmaceutical powders and ultimately better structured drug products.

Prosonix is now successfully identifying and characterizing co-crystals by applying a rational co-crystal design approach, in-depth crystallization expertise and characterisation using a number of analytical techniques.

Moreover, our proprietary sonocrystallization technologies including UMAX^® (Ultrasound Mediated Amorphous to Crystalline transition) and DISCUS^® (Dispersive Crystallization with Ultrasound) can be used for co-crystal manufacture at any scale.

For example UMAX^® processing has successfully been applied to the production of a number of co-crystals including carbamazepine:saccharin (1:1) and indamethacin:saccharin (1:1) co-crystals.

The co-crystal products obtained by the UMAX^® processing are of very high purity and can be prepared to whatever particle size distribution is demanded by our clients.

Our co-crystallization strategy for both in-house R&D and our clients own products follows several fundamental steps, as shown.

We believe our proprietary UMAX^® and other sonocrystallization technologies are set to revolutionize the manufacturing of pharmaceutical co-crystals suitable for use in inhaled / oral medicine.

Our co-crystallization service is now available for partnering and evaluation.