Vibrational and thermal properties of crystalline topiramate

Abstract

O topiramato, que é uma poderosa droga anticonvulsiva utilizada para controlar os sintomas da epilepsia, foi investigado pelas técnicas de difratometria de raios X, FT-Raman, FT-infravermelho, análise termogravimétrica, análise térmica diferencial e cálculos com teoria do funcional de densidade. A partir deste estudo foi possível identificar a maior parte das bandas observadas nos espectros Raman e infravermelho. Das análises térmicas, efetuadas da temperatura ambiente até 900 o C, verificou-se que o material não apresenta nenhuma mudança de fase e que a decomposição ocorre num processo exotérmico de duas etapas.Topiramate, a powerful anticonvulsant drug, was investigated by X-ray diffractometry, FT-Raman, FT-IR, TGA and DTA techniques as well as by DFT calculations. From this study it was possible to tentatively assign most of the normal vibrational modes of the crystal. Thermal analysis from room temperature to 900 o C shows that the material does not present any structural phase transition and that the decomposition occurs in a two-step exothermic process. Keywords: organic crystals, vibrational spectra, X-ray diffraction, thermodynamic properties IntroductionEpilepsy is a set of neurological disorders that range from brief cessation of responsiveness to severe muscle spasms with a loss of conciousness. In the last years some drugs have been tailored with the objective of controlling epileptic symptoms, the so called anticonvulsant drugs. Among these drugs, one of the most efficient and powerful as antiepileptic is topiramate, 1 a crystalline white powder of molecular formula C 12 H 21 NO 8 S and structural formula shown in Figure 1. Topiramate (2,3:4,5-bis-Omethylethylidene-β-D-fructopyranose sulfamate) is derived from a monosaccharide by addition of a sulfamate group, and was discovered by Maryanoff et al. 2 in 1987, exhibiting a remarkable anticonvulsant activity. Since the late 1990s it has been used to treat epilepsy (its trade names are Topamax®, Topimax® or Topamac®) and has recently also been used to prevent migraine headaches in adults. 3 In the last years, many works have reported physicalchemical characterization of drugs in order to determine several important aspects, such as the influence of processing and formulation of solid pharmaceuticals, polymorphisms, the relationship between physical structures and their properties, among others. 4 Although many clinical properties of topiramate have already been investigated, very few papers address its structural and physical-chemical properties. One of these is from Vibrational and Thermal Properties of Crystalline Topiramate J. Braz. Chem. Soc. 1608 Kubicki et al., 5 which presents a detailed description of its crystal structure obtained from X-ray diffraction data. The crystal belongs to the orthorhombic system, space group P2 1 2 1 2 1 , with cell parameters a = 7.2497 Å, b = 11.0007 Å, c = 19.6291 Å, and Z = 4. Also, there are some works published on stability analysis of topiramate, 6 especially on the development of techniques to detect sul...