07 Advanced technologies THE SYNTHESIS AND CHARACTERIZATION OF IRON(II) FUMARATE AND ITS INCLUSION COMPLEXES WITH CYCLODEXTRINS Agneš J. Kapor 1 , Ljubiša B. Nikolić 2 , Vesna D. Nikolić 2* , Mihajlo Z. Stanković 2 , Milorad D.Cakić 2 , Dušica P. Ilić 2 , Ivana I. Mladenović-Ranisavljević 2 , Ivan S. Ristić 3 1 Faculty of Sciences, Department of Physics, University of Novi Sad, Novi Sad, Serbia 2 Faculty of Technology, University of Niš, Leskovac, Serbia 3 Faculty of Technology, University of Novi Sad, Serbia This paper presents a synthesis of iron(II) fumarate based on the conversion of fumaric acid into disodium fumarate in molar ratio of 1:2 by the neutralization process. Disodium fumarate, as intermediate, in a nitrogen atmosphere it re- acts with iron(II)-sulfate in molar ratio of 1:1. The obtained iron(II) fumarate is a reddish precipitate with the purity of 98 %. In order to improve the poor solubil- ity of the synthesized iron(II) fumarate, inclusion complexes with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared by using a co-precipitation method in molar ratio of 1:1. The characterization of inclu- sion complexes, iron(II) fumarate and cyclodextrin was done out by using Fou- rier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-Ray Diffraction (XRD) methods. The solubility of iron(II) fumarate in the pure state and in the complexes was determined by UV/VIS method. The best solubility was obtained for the 2-hydroxypropyl-β-cyclodextrin: iron(II) fumarate complex. Keywords: antianemic, iron(II) fumarate, inclusion complexes, β-cyclodextrin, 2-hydroxypropyl-β- cyclodextrin, solubility Introduction Many products based on organic and inorganic com- pounds of iron(II) and iron(III) are used for the treatment of sideropenic anemia. Depending on the type of anemia and its etiology, the treatment is carried out by giving oral or parenteral iron preparations. Oral therapy, as more suit- able in medical practice, is applied only in terms of good iron absorption from the gastrointestinal tract and if no side effects such as nausea, pain or vomiting common for oral iron preparations appear [1-3]. Iron(II) compounds have better absorption and they are mainly used in oral therapy [4]. However, and almost without exception, all oral preparations in use cause more or less side effects. The pharmaceutical industry strives to different formulations of final products (micro-encapsu- lation, the use of plastic matrix, additives, etc..) to reduce side effects, but overall, the currently achieved results have not been satisfactory [5, 6]. The presence of addi- tives in formulations for improving the iron absorption is being particularly criticized. The tests conducted with iron salts and organic acids labeled with the 59 Fe isotope sug- gest that the addition of promoters does not lead to im- provements in products performances but has only a com- mercial effect [7]. Iron compounds which have been used for therapy nowadays can be classified into several groups of iron salts, iron chelates, polynuclear iron(III) complexes and carbohydrates. Iron(II) fumarate is the iron(II) salt of fumaric acid. It is a fine reddish orange to reddish-brown granular powder, hardly soluble in water, with the solubility of 0.14 g/100 cm 3 and of very low solubility in alcohol, less than 0.01 g/100 cm 3 . It is stable even at temperatures of above 200 o C. A precur- sor for the synthesis of iron(II) fumarate is a fumaric acid, trans-1,2-ethylenedicarboxylic acid, the structural formula of which is given in Figure 1a. The solubility of this acid in water at room temperature is very small, it is relatively nonvolatile, does not yield anhydride and is weaker than a cis-isomer maleic acid. The structure of iron(II) fumarate is shown in Figure 1 b. (ORIGINAL SCIENTIFIC PAPER) UDC 577.164.1 *Author address: Vesna Nikolić, Faculty of Technology, 16000 Leskovac, Bulevar oslobođenja 124, Serbia e-mail: nvesna@yahoo.com The manucsript received: March, 05, 2012. Paper accepted: Jun, 18, 2012. 1(1) (2012), 07-15