Pharmaceutical co-crystals

Almarsson, 0., Zaworotko, M. J., Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines Chem. Commun. 2004, 1889-1896. 

M.K. Stanton, S. Tufekcic, C. Morgan, A. Bak, Drug substance and former structure property relationships in 15 diverse pharmaceutical co-crystals, Cryst. Growth Des. 9 (2009) 1344-1352. 

Vishweshwar P, McMahon JA, Zaworotko MJ. Crystal engineering of pharmaceutical co-crystals. In Tickink ERT, Vittal JJ, eds. Frontiers in Crystal Engineering. New Jersey John Wiley Ltd, 2006 25-49. 

Pharmaceutical co-crystals, as an emerging class of pharmaceutical material, provide an alternative to the salt form for drug molecules without ionizable groups [19, 20]. The major goal is to achieve potential improvement of physical properties (e.g., enhanced dissolution rates, mechanical properties, avoidance of moisture sensitivity. 

S. Velaga, S. Basavoju, and D. Bostroem, Norfloxacin saccharinate-saccharin dihydrate co-crystal - A new pharmaceutical co-crystal with an organic counter ion, J. Mol Struct., 889, 150-153 (2008). 

W. Jones, W. Motherwell, and A. Trask, Pharmaceutical co-crystals an emerging approach to physical property enhancement, MRS Bull, 31, 875-879 (2006). 

Guidance for Industry Regulatory Classification of Pharmaceutical Co-Crystals-, Food and Drug Administration Silver Spring, MD, December 2011. 

K. K. Arora and M. J. Zaworotko, in Polymorphism in Pharmaceutical Solids, ed. H. G. Brittain, Pharmaceutical co-crystals A new opportunity in pharmaceutical science for a long-known but little studied class of compounds. Informa Healthcare, New York, 2009, vol. 2, p. 281. 

Tran TT-D, Tran PH-L, Choi H-G, Han H-K, Lee B-J (2010) The roles of addifiers in solid dispersions and physical mixtures. Int J Pharm 384 60-66 Vasconcelos T, Sarmento B, Costa P (2007) Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 12 1068-1075 fishweshwar P, McMtihon JA, Bis JA, Zaworotko MJ (2(X)6) Pharmaceutical co-crystals. J Pharm Sci 95 499-516... 

A major reason for the popularity of pharmaceutical co-crystals in industry is that they lend themselves well to patent protection. They admirably satisfy the three criteria of patentability, namely novelty, non-obviousness and utility. A co-crystal almost always satisfies the novelty criterion because it is a new composition of matter. Non-obviousness is provided by the fact that the identification of the co-former is hardly ever routine, unlike say salt formation wherein an acid is obviously required to make a salt from a base. Utility is generally the only criterion that must be established but it is often easy to demonstrate—usually it is the lack of a particular attribute (solubility, bioavailability, dissolution profile, good shelf life) that has led to the identification of a pharmaceutical co-crystal. With respect to patentability, co-erystals offer opportunities vis-d-vis polymorphs. They are clearly new substances, problems of inherent anticipation are not likely to arise so often and more of them can be made for any given API, expanding the pharmaceutical space around it and consequently the types of advantageous properties that may be accessed. 

The toxicity of the co-crystal formers was not considered, since the purpose of the experiments was to confirm the physical significance of the results from the database study. Of course, only non-toxic substances can be used when developing a pharmaceutical co-crystal, but this diiference is expected to have... 

Figure 8.5 Pharmaceutical co-crystal components and a fragment of the solid-state co-crystal structure for (a) theobromine and malonic acid, (b) theophylline and D- and DL-malic acids and (c) AMG-517 and sorbic add. - ...

Examples of Pharmaceutical Co-crystal Synthesis and Screening Using Mechanochemistry... 

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