Cocrystal Systems of Pharmaceutical Interest

Cocrystal Systems of Pharmaceutical Interest 2007-2008 Harry G. Brittain... 

H.G. Brittain, Cocrystal systems of pharmaceutical interest 2007-2008, in H.G. Brittain (Ed.), Profiles of Drug Substances, Excipients, and Related Methodology, vol. 35, Elsevier Academic Press, Amsterdam, 2010, pp. 373-390. 

Contents 1. Introduction 373 2. Screening for and Preparation of Cocrystal Systems 375 3. Cocrystal Systems Having Pharmaceutical Interest 377 3.1. Cocrystal systems formed by carbamazepine- type molecules 378 3.2. Cocrystal systems formed by nicotinamide with carboxylic acids 380 3.3. Cocrystal systems formed by caffeine and theophylline 382 3.4. Cocrystal systems formed by saccharin 384 3.5. Cocrystal systems formed by carboxylic acids 385 References 386... 

As cocrystal systems achieve more and more interest as new solid-state forms of active pharmaceutical ingredients, the research conducted on these systems continues to grow. As one might expect, a considerable amount of work has also been conducted on cocrystal systems of less interest to pharmaceutical scientists. The following sections will summarize... 

The current volume contains profiles on Buclizine, Chitin, Ezetimibe, Gemfloxacin, Glimepiride, Lomoxicam, Magnesium Silicate, and Tadalafil. The volume also contains a chapter reviewing the direct crystallization of enantiomers and dissociable diastereomers and a review of the literature published during 2009 that pertains to cocrystal systems having pharmaceutical interest. 

In a recent review, Shan and Zaworotko have discussed cocrystals having pharmaceutical interest, and presented several case studies that they used to demonstrate how one could enhance the solubility, bioavailability, and/or stability of drug substances [23]. The systems considered were the cocrystals of fluoxetine hydrochloride with carboxylic acids, itraconazole with dicarboxylic acids, sidenafil with acetylsalicylic acid, and melamine with cyanuric acid. One main conclusion advanced by the authors was that the use of cocrystal systems in pharmaceutical dosage forms was inevitable, and that the main questions were who would benefit and how drastic the influence on development would ultimately turn out to be. 

Of course, not all methods of cocrystal production require the use of auxiliary solvents. Thermal microscopy was used to determine if a particular carboxylic acid could cocrystallize with 2-[4-(4-chloro-2-fluorophe-noxy)phenyl]pyrimidine-4-carboxamide, with positive interactions being detected as crystalline material being produced at the binary interface [35]. Once identified, authentic cocrystal systems were prepared on a larger scale using solution-phase methods. In a similar study, hot-state microscopy was used to screen the possible interactions of nicotinamide with seven compounds of pharmaceutical interest that contained carboxylic acid groups [36]. A screening method for cocrystal formation based on differential scanning calorimetry has also been described, and used to demonstrate cocrystal formation in 16 out of 20 tested binary systems [37],... 

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