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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Solid-State Supramolecular Synthesis Based on the N-H center dot center dot center dot O Heterosynthon: An Approach to Solve the Polymorphism Problem in Famotidine

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Russo, Marcos G. [1] ; Brusau, Elena V. [1] ; Ellena, Javier [2] ; Narda, Griselda E. [1]
Total Authors: 4
[1] Univ Nacl San Luis, Quim Inorgan INTEQUI Fac Quim Bioquim & Farm, RA-5700 San Luis - Argentina
[2] Univ Sao Paulo, Phys Inst Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Pharmaceutical Sciences; v. 103, n. 11, p. 3754-3763, NOV 2014.
Web of Science Citations: 2

Famotidine (FMT), a histamine H-2-receptor antagonist, is a drug commonly used in treatments of gastroesophageal diseases that presents solid-state polymorphism (A and B forms), the marketed form being the metastable polymorph B. A new stable salt was obtained by combination of FMT and maleic acid as coformer. FMT maleate (FMT-MLT) was prepared either by solvent evaporation or comilling methods. Single-crystal X-ray diffraction reveals that (FMT)(+) in FMT-MLT adopts an extended conformation that is stabilized by classical and nonclassical H-bonds. The three-dimensional packing consists of tapes along the axis b that further develop a columnar array based on H-bonds involving (FMT)(+) side chain. Nonconventional -stacking interactions between adjacent tapes were also identified. Fourier transform infrared, differential scanning calorimetry, thermogravimetric analysis, polarized light thermal microscopy, and scanning electron microscopy were employed to characterize the multicomponent complex. According to the solubility values in water and simulated gastric fluid, FMT-MLT exhibits such a performance that improves on the solubility of the commercially available polymorph. Finally, the higher stability of FMT-MLT regarding both FMT forms, as well as its easy preparation from either A or B forms or a mixture of them, also allows to consider this salt as a valuable alternative to avoid the polymorphism issue in marketed formulations containing FMT. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3754-3763, 2014 (AU)

FAPESP's process: 09/54035-4 - Facility for advanced studies of biosystems and nanostructured materials
Grantee:Igor Polikarpov
Support type: Multi-user Equipment Program