Ionic Co-crystals of Organic Molecules with Metal Halides: A New Prospect in the Solid Formulation of Active Pharmaceutical Ingredients

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• 作者：Dario Braga ; Fabrizia Grepioni ; Giulio I. Lampronti ; Lucia Maini ; Alessandro Turrina
• 刊名：Crystal Growth & Design
• 出版年：2011
• 出版时间：December 7, 2011
• 年：2011
• 卷：11
• 期：12
• 页码：5621-5627
• 全文大小：915K
• 年卷期：v.11,no.12(December 7, 2011)
• ISSN：1528-7505

文摘

Ionic co-crystals (ICCs) are constituted of inorganic salts and organic molecules. These crystals combine ionic interactions with classical supramolecular bonding such as hydrogen and dipole-bonding interactions. Such is the case of the hydrogen bonds between N鈥揌 and C鈺怬 dipoles in primary and secondary amides when these cocrystallize with an ionic material such as CaCl₂. Here, we report our results of the preparation and characterization of a series of ICCs in which the molecular component is an active pharmaceutical ingredient (API) or a precursor of APIs, namely, barbituric acid, diacetamide, malonamide, nicotinamide, and piracetam, while the inorganic salt coformer is CaCl₂. CaCl₂ has been chosen, inter alia, for its nontoxicity and potential applications in the pharmaceutical field. Preparative methods include conventional crystallizations from solution, as well as slurry and solid state techniques (grinding and kneading). All crystal structures reported herein were determined either from single crystal diffraction data or from powder diffraction data, using simulated annealing procedures. Crystalline products were analyzed by differential scanning calorimetry, thermogravimetric analysis, and variable temperature X-ray powder diffraction. Intrinsic dissolution rate measurements were also performed on nicotinamide and piracetam ICCs.