Contents lists available at ScienceDirect Applied Clay Science journal homepage: www.elsevier.com/locate/clay Research Paper Tamoxifen/montmorillonite system – Effect of the experimental conditions Dayanne T.C. Silva a , Igor E.S. Arruda a , Leandro M. França a , Denise B. França b , Maria G. Fonseca b , Monica F.L.R. Soares a , Cesar Viseras Iborra c , José Lamartine Soares-Sobrinho a, ⁎ a Department of Pharmaceutical Sciences, Universidade Federal de Pernambuco, UFPE, Campus of Recife, s/n, 50740-521 Recife, PE, Brazil b Department of Chemistry, Universidade Federal da Paraíba, UFPB, 58051-900 João Pessoa, PB, Brazil c Instituto Andaluz de Ciencias de la Tierra, CSIC- University of Granada, Av. de las Palmeras 4, 18100 Armilla, Granada, Spain ARTICLE INFO Keywords: Clays Montmorillonite Tamoxifen Hybrids Adsorption ABSTRACT A new nano system based on drug/clay minerals is sought as an alternative to the current options due to the limitations of the conventional treatment. In this study, experimental conditions, such as pH, reaction duration and initial drug concentration, were evaluated to obtain systems based on the anticancer drug tamoxifen (TMX) and montmorillonite. Equilibrium and kinetic studies were developed for montmorillonite (VHS)/TMX at pH values in the range of 1.5 to 7.0 for reaction times of 1 to 720 min and drug concentrations of 533 to 2300 mg·L -1 . The solids were characterized by using X-ray diffraction and middle infrared spectroscopy (MID). The interaction of TMX with montmorillonite was pH-dependent with a higher adsorption at pH 5.5 (402.63 mg·g -1 ). For all pH values, intercalation of the drug was the preponderant mechanism of interaction. The system was described by a pseudo-second-order model. In the equilibrium study, the data adsorption was fitted to Langmuir model. Therefore, the reaction between TMX and montmorillonite was effective, and the best experimental conditions to obtain the studied hybrids were at pH 5.5 for 720 min and 2300 mg·L -1 drug con- centration. 1. Introduction The limitations of conventional treatments for breast cancer have stimulated the development of new nano systems associated with conventional therapies, such as Tamoxifen (TMX) ((Z)-2-(para-(1,2-di- phenyl- 1 -butenyl)phenoxy)-N,N-dimethylethylamine) (Thotakura et al., 2017). TMX is a selective estrogen receptor modulator (SERM) and acts as anti-estrogen in breast tissue by interfering with the activity of estrogen, the female sex hormone that promotes the growth of cancer cells in the breast (Landeros-Martinez et al., 2017). Tamoxifen is cur- rently used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancer in pre- and post-menopausal women. Since the early 1980s, tamoxifen has been widely accepted as the first- line of endocrine therapy for metastatic disease in postmenopausal women (Ingle, 1984). Although tamoxifen is anti-estrogenic to the breast, after long-term therapy, it has exhibited several side effects on endometrial cancer, for example. Several studies have shown that one of the several side effects of tamoxifen administration is its proliferative effect on the en- dometrium (Peters-engl et al., 1999; Cohen, 2004;). Therefore, the development of new systems for tamoxifen administration has been linked to interesting strategies for physical and chemical improvements of the drug and to provide improvements in therapy aimed at a better adherence of the patient to the treatment (Carazo et al., 2018). Several studies have been performed focusing on systems for ob- taining new materials with multifunctional properties of anticancer drug delivery. These materials are different from conventional poly- mers and composites (Vivek et al., 2013; Pandey et al., 2014; Prabaharan, 2015; Shariatinia and Zahraee, 2017). In this method, clay minerals have been used as vehicles for different drugs of various pharmacological categories (Joshi et al., 2009; Chen et al., 2010; Iliescu et al., 2011; Wu et al., 2013; Liu et al., 2015; Akyuz and Akyuz, 2017; Borrego-Sánchez et al., 2017; Calabrese et al., 2017; Oliveira et al., 2017; Rapacz-Kmita et al., 2017; Türker et al., 2017; Djebbi et al., 2018). Among these minerals, such smectites as montmorillonite (Mt) were studied. Montmorillonite is a 2:1 phyllosilicate and consists structurally of an octahedral sheet of alumina (Al 2 O 3 ) between two tetrahedral si- lica (SiO 2 )(Wang et al., 2016; Djebbi et al., 2018). Due to the iso- morphic substitutions of Si 4+ by Al 3+ in the tetrahedral sheet and https://doi.org/10.1016/j.clay.2019.105142 Received 21 September 2018; Received in revised form 9 May 2019 ⁎ Corresponding author at: Department of Pharmaceutical Sciences, Universidade Federal de Pernambuco, UFPE, Campus of Recife, S. Prof. Artur de Sá, s/n, CEP 50740-521 Recife, PE, Brazil. E-mail address: joselamartine@hotmail.com (J.L. Soares-Sobrinho). Applied Clay Science 180 (2019) 105142 0169-1317/ © 2019 Elsevier B.V. All rights reserved. T