Cocrystal pharmaceutical properties

We will first describe some of the theoretical aspects for cocrystal design, followed by a summary of the pharmaceutical properties of cocrystals, including their solubility dependence on cocrystal component concentration and in some cases on solution pH. Processes for cocrystal formation will be presented by considering the factors that control cocrystallization kinetics and mechanisms in solution and in solid-state mediated processes. This article will be useful to the reader who wishes to anticipate cocrystal formation during pharmaceutical processes and storage and to those who wish to proactively discover new phases. 

While establishing molecular networks for cocrystal design and determining crystal structures is very important, the value of cocrystals of pharmaceutical components lies in the ability to tailor the functionality of materials. In contrast to polymorphs that have the same chemical composition, cocrystals do not. As such, one would expect that with cocrystals one could introduce greater changes in material properties than with polymorphs. Properties that relate to pharmaceutical performance and that can be controlled by cocrystal formation include melting point, solubility, dissolution, chemical stability, hygroscopicity, mechanical properties, and bioavailability. The cocrystals for which pharmaceutical properties have been studied are few and some of these are presented below. Clearly further research in this area is needed. 

This chapter has merely surveyed some ways in which co-crystals may translate into new patents and commercial value and has discussed some considerations for accomplishing this. It is clear that the success of co-crystals in commercialization and as new patents is tied to their unique chemical composition, crystalline structure, and properties. Engineering pharmaceutical properties using co-crystals can create new commercial value for an API and extend its patent life. This value comes from the composition of the co-crystal as well as from its crystalline form. Patenting co-crystals captures that value in the form of intellectual property. Yet, co-crystal patents have their own unique aspects to be addressed as can be seen from the discussion of the definition of cocrystal , the patentability of co-crystals, and the information needed for... 

In a demonstration of the pharmaceutical advantage that can be realized through the use of a cocrystal form of a substance, it was shown that the 1 1 cocrystal of caffeine and methyl gallate exhibited significantly improved powder compaction properties [64], The compression characteristics of the cocrystal were reported to be excellent over the entire pressure range studied, with the tablet tensile strength of the cocrystal being twice that of caffeine at pressures less than 200 MPa. The superior compaction properties of the cocrystal product were attributed to the presence of slip planes in crystal structure. 

N. Schultheiss, A. Newman, Pharmaceutical cocrystals and their physicochemical properties, Cryst. Growth Des. 9 (2009) 2950-2967. 

Cocrystals are becoming increasingly important as a means of controlling the properties of pharmaceutical solids by designing multiple component molecular networks that introduce the desired functionality. Because cocrystal design is based on supramolecular synthesis, it provides a powerful approach for the proactive discovery of novel pharmaceutical solid phases. Application of the fundamental concepts presented here on cocrystallization processes is essential for the pharmaceutical scientist to anticipate the formation of cocrystals during pharmaceutical processes and storage, as well as to develop reliable methods for cocrystal discovery and production. 

Jones W, Motherwell WDS, Trask AV (2006) Pharmaceutical cocrystals an emerging approach to physical property enhancement. MRS Bull 31 875-879. 

Co-crystals represent a novel class of crystalline solids which possess scientific and regulatory advantages along with enormous intellectual property potential. In the earlier stages of pharmaceutical process development, an efficient cocrystal screening is essential in order to determine the different possible stoichiometries and the different polymorphic forms for each stoichiometry. When all the different phases are identified, the relative stability of the solid phases in solution has to be determined. This step requires the construction of the... 

The emerging field of crystal engineering facilitates the generation of a wide range of new crystal forms of compounds without the need to invoke covalent bond breakage or formation, i.e. it enables discovery of new compositions of matter even for long known molecules that would otherwise be difficult to patent and fine tune in terms of physical properties. This contribution will focus upon the role of cocrystals in pharmaceutical science with emphasis upon the following ... 

The most useful aspect is that pharmaceutical cocrystals can be attempted to optimize the physicochemical properties of drugs such as solubility, dissolution rate, stability, tableting, and so on, without the need for covalent modification [127,128]. 

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