Review ฀ 10.1517/17425240902828304฀©฀2009฀Informa฀UK฀Ltd฀ISSN฀1742-5247฀ 333 All฀rights฀reserved:฀reproduction฀in฀whole฀or฀in฀part฀not฀permitted Pharmaceutical฀co-crystals–an฀ opportunity฀for฀drug฀product฀ enhancement Inna Miroshnyk, Sabiruddin Mirza & Niklas Sandler † † University of Helsinki, Faculty of Pharmacy, PO Box 56, FIN-00014, Finland By maximizing our understanding of materials and the relative importance of interactions on all levels (i.e., molecular, particle, powder, product), we can improve the manufacture of drug dosage forms and thus meet target specifications for mechanical durability, stability and biopharmaceutical per- formance. Pharmaceutical co-crystals are the latest material being explored in order to enhance drug properties using this bottom-up approach. In this review we provide a general introduction to pharmaceutical co-crystals. We also address common aspects of co-crystal formation, discuss screen- ing strategies and outline methodologies for co-crystal functionality. Pharmaceutical co-crystals that have a distinct solid phase possess a unique set of properties, thus co-crystal formation can act as an advantageous alternative to other solid-state modification techniques. More research is needed in order to scale up co-crystal systems and implement manufacturing of final dosage forms on large scale. Keywords: co-crystal formers, co-crystals, crystal engineering, solid-state characterization, supramolecular chemistry Expert Opin. Drug Deliv. (2009) 6(4):333-341 1.฀ Introduction Using complementary molecules to design binary compounds is one of the many applications of crystal engineering. Pharmaceutical molecules inherently contain molecular recognition sites that bind selectively to biomolecules. These sites can be used to form supramolecular self-assembling complexes with desired physico- chemical properties [1]. Pharmaceutical co-crystals–crystalline molecular complexes of two or more neutral molecules–are the latest example of how supramolecular chemistry can be used to enhance the properties of active pharmaceutical ingredi- ents (APIs), including dissolution rate, mechanical properties and stability [2]. Co-crystal formation has several potential advantages over traditional solid-state modification techniques (e.g., salt formation). For example, all types of drug molecules in theory have the capability to form co-crystals; therefore, covalent modification of APIs is unnecessary when using co-crystals. There has recently been increased activity in the area of pharmaceutical co-crystal research and a wide range of insightful studies has been published [3-21]. There is growing interest in pharmaceutical co-crystals and they are emerging as an attractive option to polymorphs, salts, solvates and crystal habit manipulation in dosage form design. When using co-crystals, the bulk material and the physicochemical properties of the API can be modified while still maintaining the intrinsic activity of the drug molecule [2]. From a physical properties perspective, a key advantage of using co-crystals to transform an API into a solid form is the possibility of achieving a high dissolution rate comparable to that of the amorphous form while maintaining the long-term chemical and physical stability that 1. Introduction 2. General aspects of co-crystal formation 3. Expert opinion 4. Conclusions