Contents lists available at ScienceDirect Applied Clay Science journal homepage: www.elsevier.com/locate/clay Research paper Synthetic clay mineral as nanocarrier of sulfamethoxazole and trimethoprim D. Hernández a , L. Lazo a , L. Valdés b , L.C. de Ménorval c , Z. Rozynek d , A. Rivera a, ⁎ a Zeolites Engineering Laboratory, Institute of Materials Science and Technology (IMRE), University of Havana, Cuba b Department of Pharmacy, Institute of Pharmacy and Food (IFAL), University of Havana, Cuba c Institut Charles Gerhardt Montpellier, Equipe Agrégats, Interface, et Matériaux pour l'Energie (AIME), Université Montpellier 2, France d Faculty of Physics, Adam Mickiewicz University, Poland ARTICLE INFO Keywords: Sulfamethoxazole Trimethoprim Antibiotics Li-fluorohectorite Synthetic clay mineral ABSTRACT In the present work the incorporation of two model drugs, sulfamethoxazole (SMX) and trimethoprim (TMP) on the Li-fluorohectorite (LiFHt), synthetic clay mineral was evaluated. Understanding the interactions established between these two antibiotics – which are complementary forms from the pharmaceutical point of view – and LiFHt, allows to develop new drug delivery formulations with both drugs in the same support. The quantification of both drugs was followed by ultraviolet (UV) spectroscopy. For the interaction clay mineral-drugs, different physical-chemical parameters-pH, drug initial concentration, temperature and interaction time-were studied. The results showed that, for both drugs, the best clay mineral-drug nanocomposites were obtained at acid pH, room temperature during 1 h, and initial drug concentration of 3 mg/mL. The resulting clay mineral-drug na- nocomposites were characterized by X-ray diffraction (XRD), infrared (IR) spectroscopy and thermal gravimetry (TG). It was corroborated by XRD that the TMP was truly intercalated into the clay mineral. However, SMX seems to be adsorbed onto the clay mineral surface. For the LiFHt-TMP nanocomposite, IR suggested clay mi- neral-drug interactions via amine groups of the TMP. No significant changes in the IR spectrum for the LiFHt- SMX were observed. The drug release profiles showed to follow the pharmaceutical standards, and suggested the possibility to design formulations of drug delivery using LiFHt as carrier. 1. Introduction It is well known that conventional release dosage forms provide an immediate drugs release, without much control of the release rate. In order to obtain therapeutically effective plasmatic concentrations, and to avoid significant fluctuations in the plasmatic drug levels, it is ne- cessary to achieve dosage control. Failing to do so can lead to drug levels in the organism, by excess or defect, resulting in undesirable side effects, or in the lack of therapeutic benefits for the patient. Such dis- advantages can be reverted through the use of materials to control the drugs release (Siegel and Rathbone, 2012; de Sousa et al., 2013). Several reports about the use of clays and clay minerals in the pharmaceutical industry like active principles and/or excipients can be found (Aguzzi et al., 2007; de Sousa et al., 2013). Among the many benefits offered by clays, is their safety for the human health. The de- sirable physical and chemical properties of clay minerals-as ad- sorbents and ion exchangers-make them play a substantial role in pharmaceutical formulations (Aguzzi et al., 2007). For example, clays from the smectite family have been used as support materials in drug slow release systems. However, the use of synthetic clay minerals offers the possibility to optimize the conditions for the incorporation of model drugs, because this way the interference of spurious phases in the in- terpretation of the results is avoided. The Li-fluorohectorite, that be- longs to the smectite group, is a 2:1 clay mineral with a negative charge net where a fraction of Mg 2+ ions are substituted by Li + in trioctahe- dral sites resulting in a negative structural charge of -1.2 electrons per unit cell (Kaviratna et al., 1996). It is compensated by exchangeable hydrated cations, i.e., Li located between clay layers allowing their stacking. The stacks can swell in the presence of water, which may enter the interlayer space, increasing the distance between layers. Based on the swelling property of this clay mineral, a few studies about its use as support system for pharmaceutical applications have been reported (Rivera et al., 2016; Valdés et al., 2016, 2017a, 2017b; dos Santos et al., 2017). Trimethoprim (TMP) and sulfamethoxazole (SMX) are com- plementary pharmaceutical forms. The synergy between both drugs was first described in a series of in vitro and in vivo experiments published in the late 1960s (Maddileti et al., 2015). TMP or 2,4-diamino-5-(3,4,5- trimethoxybenzyl)pyrimidine is a broad spectrum, synthetic anti- bacterial agent, which acts as an inhibitor of bacterial dihydrofolate https://doi.org/10.1016/j.clay.2018.03.016 Received 14 November 2017; Received in revised form 6 March 2018; Accepted 9 March 2018 ⁎ Corresponding author. E-mail address: aramis@imre.uh.cu (A. Rivera). Applied Clay Science 161 (2018) 395–403 Available online 26 May 2018 0169-1317/ © 2018 Elsevier B.V. All rights reserved. T