JOURNAL OF RAMAN SPECTROSCOPY J. Raman Spectrosc. (2008) Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/jrs.1952 Polymorphism incidence in commercial tablets of mebendazole: a vibrational spectroscopy investigation A. P. Ayala, 1* H. W. Siesler 2 and S. L. Cuffini 3 1 Departamento de F´ ısica, Universidade Federal do Cear ´ a, C. P. 6030, 60.455-900 Fortaleza, CE, Brazil 2 Department of Physical Chemistry, University of Duisburg-Essen, Essen D45117, Germany 3 Agencia C ´ ordoba Ciencia, CEPROCOR, C ´ ordoba, Argentine Received 1 November 2007; Accepted 19 January 2008 Mebendazole is a broad spectrum anthelminthic drug, which is widely used in large scale deworming programmes. This active pharmaceutical ingredient exhibits three crystal forms, namely, polymorphs A, B, and C. Therapeutic trials suggested that the most stable form, polymorph A, is inactive. However, the dissolution test normally used as a quality control tool is not able to discriminate among the polymorphs of mebendazole. In this work, the ability of the vibrational spectroscopic techniques (mid and nearinfrared absorption and Raman scattering) for the identification of the crystal form of this compound is evaluated. On the basis of these observations, this methodology is applied to determine the polymorphs of MBZ used in the formulation of the commercial tablets available in the Brazilian and German markets. Copyright  2008 John Wiley & Sons, Ltd. KEYWORDS: mebendazole; polymorphism; Raman scattering; infrared spectroscopy; near-infrared spectroscopy INTRODUCTION Mebendazole (MBZ) (methyl 5-benzoyl-1H-benzimidazol-2- yl carbamate, Fig. 1) is a synthetic broad spectrum benz- imidazole carbamate anthelmintic drug used for more than 20 years in human and veterinarian medicine to treat a variety of parasitic infestations. MBZ is active against nema- todes and cetodes, 1 being indicated in the treatment of single or mixed infestation by Enterobius vermicularis (pin- worm), Trichuris trichiura (whipworm), Ascaris lumbricoides (roundworm), Ancylostoma duodenal and Necator americanus (hookworms), Strongyloides stercoralis and Taenia spp. The importance of these infections is evidenced by recent esti- mates indicating that one quarter of the world’s population is infected with one or more of these parasites, 2,3 giving rise to a combined disease burden that might be as great as those of malaria or tuberculosis. 4,5 The broad spectrum of activity, high efficacy, ease of administration and low costs generic versions exhibited by MBZ mean that it is now widely used in large scale deworming programmes, most of them focused to school-aged children in developing countries. 6–8 L Correspondence to: A. P. Ayala, Departamento de F´ ısica, Universidade Federal do Cear´ a, C. P. 6030, 60.455-900 Fortaleza, CE, Brazil. E-mail: ayala@fisica.ufc.br One factor that may contribute to the variability in the effi- cacy of a pharmaceutical formulation is the polymorphism of the active pharmaceutical ingredient (API). Polymorphism is the ability of a chemical compound to exist in more than one crystalline form. 9 The different structural arrangements of the drug are followed by changes in physicochemical prop- erties, which can affect its bioavailability, manufacturability, purification, stability, and other performance characteris- tics of the API. 10 Considering the benzimidazole carbamates commonly applied in deworming programmes, MBZ and albendazole, just the former exhibit polymorphism. In the solid state, MBZ crystallizes in three polymorphic forms, namely polymorphs A, B, and C. Several authors pointed out possible differences in the bioavailability of the polymorphs of MBZ. 11,12 Even though some discrepancies are reported in the literature about the relative solubility of forms B and C, all the authors agree that form A is the least soluble one. 11,13,14 Thus form C is pharmaceutically preferred since its solu- bility is sufficient enough to ensure optimal bioavailability without exhibiting the toxicity associated to form B. 11,13 – 15 Furthermore, a therapeutic trial in 958 school-aged children in Thailand using a placebo and the MBZ polymorphs A and C suggested that form A has similar efficacy than the placebo in controlling hookworm and whipworm infections. 11 Other authors also reported on the polymorph dependence of the Copyright  2008 John Wiley & Sons, Ltd.