X-ray diffraction data of tibolone  4 isomer „isotibolone… Selma Gutierrez Antonio, 1,a Fabio Furlan Ferreira, 2 Gabriel Lima Barros Araujo, 3 Jivaldo do Rosario Matos, 4 and Carlos de Oliveira Paiva-Santos 1 1 Departamento de Físico Química, Instituto de Química, Universidade Estadual Paulista, Caixa Postal 355, 14801-970 Araraquara, SP, Brazil 2 Laboratório Nacional de Luz Síncrotron, Caixa Postal 6192, 13083-970 Campinas, SP, Brazil 3 Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil 4 Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, Av. Lineu Prestes, 748, Sala 0801, 05508-900 São Paulo, SP, Brazil Received 28 July 2009; accepted 15 September 2009 Tibolone is used for hormone reposition of postmenopause women and isotibolone is considered the major degradation product of tibolone. Isotibolone can also be present in tibolone API raw materials due to some inadequate synthesis. Its presence is then necessary to be identified and quantified in the quality control of both API and drug products. In this work we present the indexing of an isotibolone X-ray diffraction pattern measured with synchrotron light  = 1.2407 Å in the transmission mode. The characterization of the isotibolone sample by IR spectroscopy, elemental analysis, and thermal analysis are also presented. The isotibolone crystallographic data are a =6.8066 Å, b =20.7350 Å, c =6.4489 Å,  = 76.428°, V = 884.75 Å 3 , and space group P2 1 ,  o =1.187 g cm -3 , Z =2. © 2009 International Centre for Diffraction Data. DOI: 10.1154/1.3257612 Key words: isotibolone, hormone, indexing, X-ray powder diffraction, synchrotron radiation I. INTRODUCTION Tibolone IUPAC name 7 ,17-17-hydroxy-7- methyl-19-nor-17-pregn-510-en-20-yn-3-one, C 21 H 28 O 2  is a synthetic steroid used to relieve hypo-oestrogenic symp- toms and protect against bone loss in postmenopausal women. This steroid is considered an unstable substance due to isomerization into a compound known as isotibolone iso- mer  4 or Org OM38Figure 1 and great effort has been carried out by pharmaceutical industries in order to reduce isotibolone to desired levels during its synthesis Kirchholtes et al., 2000. The isomer is formed at high-temperature ex- posure and/or acidic conditions. The isomerization mecha- nism involves the rearrangement on the A-ring of the double bound from carbon atoms 5–10 to 4–5 Boerrigter et al., 2002. Another problem, according to the patent EP 1121375 B1 Kirchholtes et al., 2000, is that the isotibolone content increases during the dosage unit preparation. According to example 2 of the cited patent, tibolone containing less than 0.1% isotibolone has been prepared. However, the content of isotibolone in the freshly prepared pharmaceutical formula- tion was already 0.4% and 1.6% after 6 months Van Engel- gem and Marechal, 2005. The end of shelf-life specification with respect to the amount of isotibolone formed during stor- age is 5% and a minimum acceptable shelf-life period for these dosage units is 1 yr Kirchholtes et al., 2000. X-ray powder diffraction and the Rietveld method are powerful tools for the characterization of pharmaceuticals and have been successfully used in the analysis of carbam- azepine Iyengar et al., 2001, D-Mannitol Botez et al., 2003, and paracetamol Dong et al., 2008 among others. However, the Rietveld method requires the knowledge of the crystal structure of all crystalline phases present in the pow- der. Recently, Scarlett and Madsen 2006 proposed a method for the quantitative phase analysis in which only partial or no crystal structure is required, although it requires the pattern decomposition, and, when the unit cell param- eters are known, it is possible to correct for the effects of preferred orientation, which is very common with pharma- ceuticals. The method can provide the same result of the Rietveld method. Thus, the indexing of powder X-ray dif- fraction of drugs is very important for the research and qual- ity control of pharmaceuticals compounds even when the crystal structure is not known. This work aims to character- ize an isotibolone sample obtained by isomerization of the commercial tibolone sample in strong acid media and it also presents the indexing of isotibolone. II. EXPERIMENTAL The tibolone sample was kindly donated by a Brazilian pharmaceutical company. The isotibolone sample was ob- tained by isomerization of the commercial tibolone sample in strong acid media. The characterization of the isotibolone sample was carried out by elemental analysis EA and ther- mal analysis TG/DSC and FTIR spectroscopy. A. Elemental analysis Carbon and hydrogen contents were determined by el- emental analysis using a Perkin Elmer CHN Analyzer Model 2400. The accuracy of the analyses was + / -0.3% absolute. B. Infrared spectroscopy The IR absorption spectra of the isotibolone were ob- tained at room temperature in the range 4000 to 400 cm -1 in KBr pellets using a Nicolet spectrophotometer, model Magna 550. a Author to whom correspondence should be addressed. Electronic mail: selma_ga@yahoo.com.br 337 337 Powder Diffraction 24 4, December 2009 0885-7156/2009/244/337/6/$25.00 © 2009 JCPDS-ICDD