Adsorption of propranolol onto montmorillonite: Kinetic, isotherm and pH studies

1 ADSORPTION OF PROPRANOLOL ONTO MONTMORILLONITE: 1 KINETIC, ISOTHERM AND pH STUDIES 2 María del Mar Orta1, Julia Martín2*, Santiago Medina-Carrasco3, Juan Luis Santos2, 3 Irene Aparicio2, Esteban Alonso2 4 1Department of Analytical Chemistry, Faculty of Pharmacy, University of Seville, E-5 41012 Seville, Spain. 6 2Department of Analytical Chemistry, Escuela Politécnica Superior, University of 7 Seville. E–41011 Seville, Spain. 8 3X-Ray Laboratory (CITIUS), University of Seville, E-41012 Seville, Spain. 9 10 11 12 13 Corresponding author: Julia Martín 14 Address: 15 Department of Analytical Chemistry, Escuela Politécnica Superior, University of 16 Seville. C/ Virgen de África, 7, E–41011 Seville, Spain 17 E-mail: [email protected] 18 Phone number: +34-9-5455-6250 19 20 21 22 23 24 25 *Revised manuscript with no changes marked Click here to view linked References 2 Abstract 26 The objective of this study was to explore the potential use of the smectite clay mineral 27 montmorillonite (Mt) as adsorbent in the removal of water containing the emerging 28 compound propranolol. The Mt was deeply characterized by X-ray diffraction (XRD), 29 Zeta potential and thermogravimetric analysis (DSC-TG), before and after adsorption 30 experiments, and their isotherms and kinetic models were fitted to assess the adsorption 31 of propranolol. 32 The incorporation of propranolol in the interlayer was demonstrated by XRD and DSC-33 TG. The results obtained by Zeta potential indicated no adsorption of propranolol in the 34 surface. Kinetic of propranolol adsorption onto Mt was evaluated using pseudo-first-35 order, pseudo-second-order, intra-particle diffusion and Elovich models. Pseudo-second 36 order was the kinetic model that best described the adsorption of propranolol (R2> 37 0.999). It was possible to obtain a removal efficiency of approximately 96% in less than 38 1 minute. The adsorption equilibrium isotherm was fitted with the Langmuir, 39 Freundlich and Dubinin-Radushkevitch mathematical models to obtain the respective 40 parameters. Freundlich and Dubinin-Radushkevitch were the models that best fitted the 41 experimental data (R2> 0.999). Due to the cationic form of propranolol, the adsorption 42 by ionic exchange between charged propranolol and sodium cations onto the interlayer 43 space was the most favorable pathway proposed. Results indicate that adsorption onto 44 Mt proved to be an efficient method for removing propranolol, thus being a viable 45 alternative for the treatment of water contaminated with this drug. 46 47 Keywords: Propranolol; Montmorillonite; Adsorption; Water samples 48 49 50 3 1. Introduction 51 Water pollution by pharmaceutically active compounds is increasing in an alarming way 52 (Basheer et al., 2018; Mompelat et al., 2009). Among various therapeutic groups, β-53 blockers are being used worldwide due to the increasing number of patients suffering 54 from cardiovascular diseases (Ali et al., 2017; Ding et al., 2015). Several of these 55 medicines, propranolol included, are in the top 200 prescribed medications 56 (Maszkowska et al., 2014; Huggett et al., 2003). Propranolol is used as a hydrochloride 57 salt in the treatment of hypertension, pheochromocytoma, angina pectoris, myocardial 58 infarction and cardiac arrhythmia. It is also used to control hypertrophic 59 cardiomyopathy, to control symptoms of sympathetic hyperactivity when treating 60 hyperthyroidism, anxiety disorders, and tremor (Soni, 2014). 61 This drug may originate from hospital effluent, wastewater treatment plants, 62 pharmaceutical industry waste, and excretion after drug administration to people or 63 household surplus drugs' disposal (Deblonde et al., 2011). Its widespread use, together 64 with its often-incomplete metabolism (Maszkowska et al., 2014), means that 65 propranolol is commonly detected in sewage effluents and surface waters at 66 concentration levels that range from ng/L to μg/L (Liu et al., 2018; Petrie et al., 2015; 67 Maszkowska et al., 2014; Lopez-Serna et al., 2013; Santos et al., 2013; Deblonde et al., 68 2011). The process used in conventional wastewater treatment plants (WWTP) cannot 69 remove this compound efficiently (Gao et al., 2018; Gabet-Giraud et al., 2010; Santos et 70 al., 2013). For example, a study conducted by Santos et al. (2013) in effluent 71 wastewaters from four different hospitals located in Coimbra (Portugal) showed the 72 presence of different drugs, among them propranolol, in all hospitals samples analyzed 73 and also in the WWTP influent and effluent. The removal efficiency for β-blockers 74 was less than 17%. In another study carried out by Grover et al. (2011), a full-scale 75 4 granular activated carbon plant treating a WWTP effluent was assessed in terms of 76 removal efficiency of pharmaceuticals (Grover et al., 2011). Higher removal efficiency 77 (84–99%) was observed for mebeverine, indomethacine, and diclofenac, while 78 carbamazepine and propranolol displayed much less removal efficiency (17–23%). 79 Additionally, due to its characteristic of persistence against natural attenuation, it may 80 be maintained in the environment for a long period of time (Gao et al., 2018). Some 81 studies have suggested that propranolol may cause adverse effects on various aquatic 82 organisms (Ding et al., 2015; Maszkowska et al., 2014; Crane et al., 2006; Falconer et 83 al., 2006; Fent et al., 2006; Ferrari et al., 2004; Huggett et al., 2002). Propranolol has 84 the highest acute and chronic toxicity within the class of β-blockers (Maszkowska et al., 85 2014; Brausch et al., 2012; Fent et al., 2006; Stanley et al., 2006; Huggett et al., 2002). 86 In addition, propranolol is also known as an effective antagonist for 5-HT 87 (hydroxytryptamine) receptor, which is a potential target receptor in wildlife (Alexander 88 and Wood, 1987). The endocrine-disrupting potential of propranolol on aquatic 89 organisms was recently emphasized by Massarsky et al. (2011). This is an emerging 90 issue for the environment, and it can pose a new challenge to water treatment processes. 91 Several techniques are being studied to treat waters that are contaminated with 92 pharmaceutically active compounds such as photolysis, photo-Fenton, photocatalysis, 93 ozonation, nanofiltration and adsorption (Tarpani and Azapagic, 2018; Gao et al., 2018; 94 Rodríguez-Narváez et al., 2017). Adsorption becomes an interesting alternative for the 95 treatment of water that is contaminated with pharmaceuticals, since it is versatile, easy 96 to operate and efficient in removing many pharmaceutical compounds (Singh et al., 97 2018). In view of this, the use of natural clays as adsorbents becomes attractive due to 98 their high capacity to remove a great variety of dissolved organic and inorganic 99 contaminants and to their large surface area, pore structure and thermal stability, which 100 5 improves their ability to remove various contaminants from aqueous media (Lozano-101 Morales et al., 2018). Montmorillonite (Mt), a smectite clay mineral, has attracted great 102 interest in the biomedical field because of its high cation exchange capacity, easy 103 degradation, large specific surface area, low price, easy availability, good adsorption 104 capacity, and good biocompatibility (Gamba et al., 2015; Jiang et al., 2012). Mt is 105 widely used in pharmaceutical applications (Farhadnejad et al., 2018; Ullah et al., 2016; 106 Sánchez Martín et al., 1981). For example, Farhadnejad et al. (2018) designed and 107 characterizated a nanocomposite hydrogel beads, based on carboxymethyl cellulose 108 (CMC) and Mt-propranolol nanohybrid, for propranolol controlled release. Results 109 indicated that the Mt-propranolol/CMC nanocomposite beads had high stability against 110 stomach acid and a sustained- and controlled-release profile for propranolol under the 111 simulated intestinal conditions. Besides clay minerals, graphene oxide, layered double 112 hydroxides, mesoporous silica nanocontainers and oxide metallic and metallic 113 nanoparticles have also evaluated to enhance the mechanical strength and stability of 114 hydrogel compounds and decrease the drug release rate and burst initial drug release 115 (Farhadnejad et al., 2018; Kuthati et al., 2015). Furthermore, Mt has also been used as 116 an adsorbent for the removal of organic pollutants such as pesticides and emerging 117 pollutants (Martín et al., 2019; Martín et al., 2018; Orta et al., 2018; Gamba et al., 2015; 118 Marco-Brown et al., 2014; Rauf et al., 2012), heavy metals ions (Barbier et al., 2000) or 119 organic compounds such as antibiotics (Parolo et al., 2013) from water samples. Mt 120 adsorbs cationic organic pollutants through ion-exchange processes (Gamba et al., 121 2015), while anionic pollutants interact with the positively charged clay edges and 122 therefore they are only so slightly absorbed; besides, the repulsion that is established 123 with the negatively charged silicate surface also results in a certain level of desorption 124 6 (Sannino et al., 1997). To our knowledge, there is no published research regarding the 125 use of Mt for the removal of β-blockers. 126 The aim of this study was to explore the potential use of Mt as an adsorbent for the 127 decontamination of water containing the emerging compound propranolol. Mt was 128 deeply characterized by X-ray diffraction (XRD), Zeta potential and differential 129 scanning calorimetry and thermogravimetric analysis (DSC-TG), before and after the 130 adsorption experiments. Their isotherms and kinetic models were fitted to assess the 131 adsorption of propranolol. 132 133 2. Materials and methods 134 2.1. Materials and reagents 135 Mt provided by Castiglioni Pes y Cia, from North Patagonia, Argentina, was used as 136 receiver. Previous studies had determined its mineralogy and chemical composition 137 (Magnoli et al., 2008). XRD and chemical analysis indicated that the sample contained 138 Na Mt (>99%) with quartz and feldspars as minor phases. The structural formula 139 obtained from the chemical analysis was [(Si3.83Al0.11)(Al1.43Fe3+0.28Mg0.30)O10(OH)2] 140 Na0.41 The ati ni e han e a a it dete ined the u-141 t ieth enetet a ine eth d e et al., 2006) was 0.8250 ± 0.0007 mmol/g of 142 clay. 143 HPLC-grade, acetonitrile and water were supplied by Romil Ltd. (Barcelona, Spain). 144 Hydrochloric acid, sodium hydroxide and formic acid were obtained from Panreac 145 (Barcelona, Spain). Ammonium formate was purchased from Sigma-Aldrich 146 (Steinheim, Germany). All of them were analytical grade. 147 High purity propranolol was purchased from Dr. Ehrenstorfer (Augsburg, Germany). 148 Stock standard solution of propranolol (1000 mg/L) was prepared in methanol and 149 7 stored at 4°C. Fresh working solutions at different concentration levels were prepared in 150 deionized water before each experiment. 151 152 2.2. Characterization methods 153 X-ray diffraction patterns were carried out in a Bruker D8 Advance A25 diffractometer 154 (Bruker, Germany) in Bragg-Brentano configuration. The detector was a Lynxeye PSD 155 detector (Bruker, Germany) equipped with a copper Kα radiation source (0.15405 nm 156 wavelength). Step-scan data was taken from 1° to 70° 2θ, a step width of 0.03°, time 157 per step of 0.1 s, and tube conditions of 40 kV and 30 mA. The diffractometer was 158 calibrated mechanically according to the manufacturer’s specifications and corundum 159 standard was used to check the resolution in a wide range of angles. 160 Zeta potential was obtained from the mobility of the particles using the Smoluchowski 161 equation (Smoluchowski, 1941). The Mt, before and after each adsorption experiment, 162 was suspended in water (1 g/L) and zeta potentials were measured on a Zetasizer 163 Nanosystem system (Malvern Instruments, Southborough, MA). The pH of the solution 164 was measured with a Crison GLP 21 pH meter. 165 Thermal gravimetric analyses were performed on a Q600 STD (TA instruments, USA). 166 The samples were heated from 20°C to 900°C at a scanning rate of 10°C/min in a 167 nitrogen atmosphere. 168 Liquid Chromatography-tandem mass spectrometry (LC-MS/MS) analyses were 169 performed on an Agilent 1200 series HPLC system (Agilent, USA) equipped with a 170 vacuum degasser, a binary pump, an autosampler and a thermostatic column 171 compartment. Separation of propranolol was carried out using a HALO C18 (50x4.6 172 mm i.d.; 2.7 µm) analytical column (Teknokroma, Spain) protected by a HALO C18 173 (5x4.6 mm 1.d.; 2.7 µm) guard column (Teknokroma, Spain). Elution was performed by 174 8 isocratic conditions with acetonitrile (0.1% formic acid) (50%) and a 10 mM aqueous 175 solution of ammonium formate (0.1% formic acid) (50%), at a flow rate of 0.6 mL min-1 176 with a column temperature of 30°C. 177 A 6410 triple quadrupole (QqQ) mass spectrometer (MS) equipped with an electrospray 178 ionization source (Agilent, USA) was used for detection. Ionization of analytes was 179 carried out using the following settings: MS capillary voltage, 3000 V; flow rate of the 180 drying-gas, 9 L/min; drying-gas temperature, 350ºC; and nebulizer pressure was 40 psi. 181 MassHunter software (Agilent, USA) was used for instrument control and data 182 acquisition. Compounds were analyzed in multiple reaction monitoring (MRM) mode 183 and monitored in the positive ionization mode. Two MRM transitions were selected for 184 each analyte, one was applied for quantification (260 > 116) and another for 185 confirmation (260 > 56) using a fragmentor of 114 V and an energy collision of 16 eV. 186 187 2.3. Adsorption batch experiments 188 Batch adsorption experiments of propranolol onto Mt were assessed using a batch 189 equilibrium method at 25 ºC. Solutions with different initial propranolol concentrations 190 in deionized water (10 mL) containing 20 mg of Mt were added to 20 mL glass bottle 191 with teflon screw caps. The solutions were stirred at 800 rpm and samples were taken at 192 different time interval. A pH of approximately 6.5 remained constant during the 193 adsorption process in all samples. After the contact time, the suspensions were 194 centrifuged at 8000 rpm during 15 min and supernatants filtered through a 0.22 µm 195 nylon filter. The final concentrations of propranolol remaining in the aqueous phase 196 were determined using the LC-MS/MS system. 197 The parameters affecting propranolol adsorption, such as concentration (from 0.5 to 80 198 mg/L), time (from 0 s to 7 days) and sample pH (from 1 to 12) were evaluated. Each 199 9 experiment was run in triplicate. The linearity of the method was studied by analyzing 200 standard solutions in triplicate at concentrations ranging from 0.01 μg/mL to 10000 μ201 g/mL. 202 The difference in the amount before and after adsorption reveals the amount of adsorbed 203 propranolol (q): 204 q=Ci Ceq ( ) × V m (1) 205 where V (L) is the volume of the solution, m is the weight of the clay (kg), Ci (mg/L) 206 and Ceq (mg/L) are the concentration of the propranolol in the initial and final solution, 207 respectively. Control experiments were performed without Mt and indicated the 208 negligible loss of propranolol by volatilization or by adsorption on the glass tubes. 209 The adsorption percentage was calculated as follows: 210 %adsorption =Ci Ceq Ci ×100 (2) 211 The adsorbent performance was determined by adjustment of the experimental 212 isotherms to Langmuir, Freundlich and Dubinin-Radushkevitch mathematical model 213 (Marco-Brown et al., 2014). The Langmuir model is described by the following 214 equation: 215 q=qmax KLCe 1+CeKL ( ) (3) 216 where, qmax is the maximum amount adsorbed within a monolayer (μmol/g), and KL (L/ 217 μmol) is the Langmuir dissociation constant, which is related to the adsorption energy. 218 The Freundlich model is described by Equation 4: 219 q=KFCe 1/n (4) 220 16 365 3.4. Influence of the pH on the propranolol adsorption 366 One of the most important factors which influence the adsorption behavior of any 367 adsorbent material is the pH of the solution. The adsorption of propranolol onto Mt as a 368 function of pH was investigated for pH values ranging from 1 to 12 with an initial 369 concentration of propranolol of 10 mg/L (Figure 6). The results show that the amount 370 adsorbed was independent of the pH of the solution between 2-9 (% adsorption > 94%). 371 Propranolol is a secondary amine with constant acidity (pKa) equal to 9.5 and thus the 372 species of the β-blocker present in solution at pHs ranging from 2 to 9 are mainly 373 positively charged. This phenomenon favors the adsorption process on Mt where the 374 main reaction that must take place is the exchange of the sodium ions of Mt with those 375 of the propranolol-ammonium ions of the solution. At very low pH (1) values, the 376 adsorption slightly decreased to 86%, which could indicate some substitution of sodium 377 by hydrogen ions. At pH > 9, the amine is released by hydrolysis and is precipitated 378 because of its low solubility, therefore impeding the study of adsorption at pH 12. This 379 same issue was observed by Sánchez Martín et al. (1981) when studying the interaction 380 of Mt with a constant release of propranolol. 381 382 383 4. Conclusions 384 The natural phyllosilicate Mt proved to be a suitable adsorbent for the elimination of the 385 β-blocker propranolol, being a viable alternative for the treatment of water 386 contaminated with this drug. According to the results, this adsorbent required shorter 387 equilibrium times compared with other adsorbents, reaching 96% adsorption in less than 388 one minute. It was observed that propranolol adsorption kinetics onto Mt followed the 389 17 PSO model. The adsorption capacity obtained depended on the initial concentration of 390 solute; lower values of initial concentration provided greater efficiency in the adsorption 391 process. Propranolol adsorption onto Mt was well described by the Freundlich and 392 Dubinin-Radushkevitch models (R2> 0.993), being the ionic exchange between charged 393 propranolol and inorganic cations in the free sites the most favorable pathway. 394 Additionally, the variable pH presented a low influence in the range of 1 to 9. 395 XRD, DSC-TG and potential Z were used in order to confirm the entrance of 396 propranolol onto Mt. The XRD showed a slight increase in the interlayer space after the 397 adsorption, suggesting that the retention of propranolol occurs in the interlayer space. 398 The results of the DSC-TG also corroborated the adsorption. While the results obtained 399 by Zeta potential indicated no adsorption of propranolol in the surface. 400 Studies like this one prove the potential of certain adsorbent materials for their use in 401 the industrial treatment of waters affected by different types of pollutants. Obtaining 402 universal materials, with a high elimination yield and that can be applied to a wide 403 range of contaminants, is the main challenge in this field. Therefore, the following steps 404 in this line of research would be: evaluating how these materials eliminate other 405 families of water contaminants, their application on an industrial scale and, in parallel, 406 improving the functionality of the material itself. On the other hand, its use in cleaning 407 and preconcentration stages in analytical processes is also plausible according to some 408 of the interesting properties of the materials tested. 409 410 Acknowledgements 411 This work was supported by the Spanish Ministry of Economy, Industry and 412 Competitiveness (Project No. CTM2017-82778-R) and by the University of Seville, 413 through its VI Plan Propio de Investigación. The authors are grateful to the X-ray 414 18 Laboratory and Functional Characterization Services of the Centro de Investigación 415 Tecnología e Innovación de la Universidad de Sevilla (CITIUS). 416 417 References 418 Alexander, B.S., Wood, M.D., 1987. Stereoselective blockade of central [3H] 5- 419 hydroxytryptamine binding to multiple sites (5-HT1A, 5-HT1B and 5-HT1C) by 420 mianserin and propranolol. J. Pharm. Pharmacol. 39, 664–666. 421 Ali, I., Alothman, Z.A., Alwarthan, A., 2017. Uptake of propranolol on ionic liquid iron 422 nanocomposite adsorbent: kinetic, thermodynamics and mechanism of adsorption. 423 J. Mol. Liq. 236, 205–213. 424 Barbier, F., Duc, G., Petit-Ramel, M., 2000. Adsorption of lead and cadmium ions from 425 aqueous solution to the montmorillonite/water interface, Colloids Surf. A 166, 426 153–159. 427 Basheer, A.A., 2018. New generation nano-adsorbents for the removal of emerging 428 contaminants in water, J. Mol. Liq. 261, 583–593. 429 Brausch, J.M., Connors, K.A., Brooks, B.W., Rand, G.M., 2012. Reviews of Environ- 430 mental Contamination and Toxicology. Human Pharmaceuticals in the Aquatic 431 Environment: a Review of Recent Toxicological Studies and Considerations for 432 Toxicity Testing, vol. 218. Springer, pp. 1–99. 433 Bruker, 2017. Bruker AXS GmbH, Karlsruhe, Germany Search PubMed. 434 Crane, M., Watts, C., Boucard, T., 2006. Chronic aquatic environmental risks from 435 exposure to human pharmaceuticals, Sci. Total Environ. 367, 23–41. 436 e , A., u d , J., Dohrmann, R., 2006. Traditional and novel methods for 437 esti atin the a e ha e f s e tites A a S i 34, 2−13 438 19 Deblonde, T., Cossu-Leguille, C., Hartemann, P., 2011. Emerging pollutants in 439 wastewater: a review of the literature. Int. J. Hyg Environ. Health 214, 442-448. 440 Ding, J., Lu, G., Li, G., Nie, Y., Liu, J., 2015. Biological fate and effects 441 of propranolol in an experimental aquatic food chain. Sci. Total Environ. 532, 31-442 39. 443 Falconer, I.R., Chapman, H.F., Moore, M.R., Ranmuthugala, G., 2006. Endocrine-444 disrupting compounds: a review of their challenge to sustainable and safe water 445 supply and water reuse, Environ. Toxicol. 21, 181–191. 446 Farhadnejad, H., Mortazavi, S.A., Erfan, M., Darbasizadeh, B., Motasadizadeh, H., 447 Fatahi, Y., 2018. Facile preparation and characterization of pH sensitive Mt/CMC 448 nanocomposite hydrogel beads for propranolol controlled release. Int. J. Biol. 449 Macromol. 111, 696–705. 450 Fent, K., Weston, A.A., Caminada, D., 2006. Ecotoxicology of human pharmaceuticals. 451 Aquat. Toxicol. 76, 122-159.󳮁 452 Ferrari, B., Mons, R., Vollat, B., Fraysse, B., Paxeus, N.A., 2004. Environmental risk 453 assessment of six human pharmaceuticals: are the current environmental risk 454 assess ent edu es suffi ient f the te ti n f the aquati en i n ent? 455 Environ. Toxicol. Chem. 23, 1344–1354. 456 Gabet-Giraud, V., Miege, C., Choubert, J.M., Matin Ruel, S., Coquery, M., 2010. 457 Occurrence and removal of estrogens and beta blockers by various processes in 458 wastewater treatment plants. Sci. Total Environ. 408, 4257-4269. 459 Gamba, M., Flores, F.M., Madejová, J., Sánchez, R.M.T., 2015. Comparison of imazalil 460 removal onto montmorillonite and nanomontmorillonite and adsorption surface 461 sites involved: An approach for agricultural wastewater treatment. Ind. Eng. 462 Chem. Res. 54 (5), 1529-1538. 463 20 Gao, Y.q., Gao, N.y., Yin, D.q., Tian, F.x., Zheng Q.f., 2018. Oxidation of the b-blocker 464 propranolol by UV/persulfate: Effect, mechanism and toxicity investigation. 465 Chemosphere 201, 50-58. 466 Giles, C.H., Macewan, T.H., Nakhwa, S.N., Smith, D.J., 1960. Studies in adsorption. 467 Part XI. A system of classification of solution adsorption isotherms, and its use in 468 diagnosis of adsorption mechanisms and in measurement of specific surface areas 469 of solids. J. Chem. Soc. 786, 3973–3993. 470 Grover, D.P., Zhou, J.L., Frickers, P.E., Readman, J.W., 2011. Improved removal of 471 estrogenic and pharmaceutical compounds in sewage effluent by full scale 472 granular activated carbon: impact on receiving river water. J. Hazard. Mater. 185, 473 1005–1011. 474 Haro, N.K., Del Vecchio, P., Marcilio, N.R., Feris, L.A., 2017. Removal of atenolol by 475 adsorption e Study of kinetics and equilibrium. J. Cleaner Product. 154, 214–219. 476 Ho, Y.S., McKay, G., 1999. Pseudo-second order model for sorption processes. Process 477 Biochem, 34, 451–465. 478 Huggett, D.B., Brooks, B.W., Peterson, B., Foran, C.M., Schlenk, D., 2002. Toxicity 479 ofselected beta-andrenergic receptor-blocking pharmaceuticals on aquatic 480 organisms. Arch. Environ. Contam. Toxicol. 23, 229–235. 481 Huggett, D.B., Khan, I., Foran, C.M., Schlenk, D., 2003. Determination of beta-482 adrenergic receptor blocking pharmaceuticals in United States wastewater 483 effluent. Environ. Pollut. 121(2), 199–205. 484 Jiang, J.Q., Ashekuzzaman, S.M., 2012. Development of novel inorganic adsorbent for 485 water treatment. Curr. Op. Chem. Eng. 1, 191–199. 486 21 Kuthati, Y., Kankala, R.K., Lee, C-H., 2015. Layered double hydroxide nanoparticles 487 for biomedical applications: Current status and recent prospects. Appl. Clay Sci. 488 112–113, 100–116. 489 Kyzas, G.Z., Koltsakidou, A., Nanaki, S.G., Bikiaris, D.N., Lambropoulou, D.A., 2015. 490 Removal of beta-blockers from aqueous media by adsorption onto graphene 491 oxide. Sci.Total Environ. 537, 411–420. 492 Lapides, I., Yariv, S., Golodnitsky, D., 2002. Simultaneous DTA-TG Study of 493 Montmorillonite Mechanochemically Treated with Crystal-violet. J. Therm. 494 Anal. Cal. 67, 99–112. 495 Le Bail, A., 2005. Whole powder pattern decomposition methods and applications: a 496 retrospection. Powder Diffr. 20, 316. 497 Liu, J., Dan, X., Lu, G., Shena, J., Wua, D., Yana, Z., 2018. Investigation of 498 pharmaceutically active compounds in an urban receiving water: Occurrence, fate 499 and environmental risk assessment. Ecotoxicol. Environ. Saf. 154, 214–220. 500 Lopez-Serna, R., Jurado, A., Vázquez-Suñe, E., Carrera, J., Petrovic, M., Barcelo, D., 501 2013. Occurrence of 95 pharmaceuticals and transformation products in urban 502 groundwaters underlying the metropolis of Barcelona. Spain. Environ. Pollut. 503 174, 305-315. 504 Lozano-Morales, V., Gardi, I., Nir, S., Undabeytia, T., 2018. 505 Removal of pharmaceuticals from water by clay-cationic starch sorbents. J. Clean. 506 Product. 190,703-711. 507 Magnoli, A. P., Tallone, L., Rosa, C.A.R., Dalcero, A.M., Chiacchiera, S.M., Torres 508 Sanchez, R.M., 2008. Commercial bentonites as detoxifier of broiler feed 509 nta inated with af at in A a S i 40, 63−71 510 22 Marco-Brown, J.L., Areco, M.M., Torres Sánchez, R.M., dos Santos Afonso, M., 2014. 511 Adsorption of picloram herbicide on montmorillonite: Kinetic and equilibrium 512 studies. Colloids and Surfaces A: Physicochem. Eng. Aspects. 449, 121–128. 513 Martín, J., Orta, M.M., Medina-Carrasco, S., Santos, J.L., Aparicio, I., Alonso, E., 514 2018. Removal of priority and emerging pollutants from aqueous media by 515 adsorption onto synthetic organo-funtionalized high-charge swelling micas. 516 Environ. Res. 164, 488–494. 517 Martín, J., Orta, M.M., Medina-Carrasco, S., Santos, J.L., Aparicio, I., Alonso, E., 518 2019. Evaluation of a modified mica and montmorillonite for the adsorption of 519 ibuprofen from aqueous media. Appl. Clay Sci. 171, 29-37. 520 Massarsky, A., Trudeau, V.L., Moon, T.W., 2011. β-blockers as endocrine disruptors: 521 the potential effects of human β-blockers on aquatic organisms. J. Exp. Zool. A 522 Ecol. Genet. Physiol. 315, 251–265. 523 Mas ws a, J , St te, S , Ku i s a, J , Łu as ewi , P , Mi dus ews a, K , 524 Pu ws i, A , a an, M , Wa i , M , Ste n ws i, P , iał -Bielin ska, A., 2014. 525 Beta-blockers in the environment: part I. mobility and hydrolysis study. Sci. Total 526 Environ. 493, 1112-1121. 527 Mompelat, S., Le Bot, B., Thomas, O., 2009. Occurrence and fate of pharmaceutical 528 products and by-products, from resource to drinking water. Environ. Int. 35, 803–529 814. 530 Orta, M.M., Martín J., Medina-Carrasco S., Santos J.L., Aparicio I., Alonso, E., 2018. 531 Novel synthetic clays for the adsorption of surfactants from aqueous media. J. 532 Environ. Manag. 206, 357-366. 533 23 Parolo, M.E., Avena, M.J., Savini, M.C., Baschini, M.T., Nicotra, V., 2013. Adsorption 534 and circular dichroism of tetracycline on sodium and calcium-montmorillonites, 535 Colloids Surf. A 417, 57–64. 536 Petrie, B., Barden, R., Kasprzyk-Hordern, B., 2015. A review on emerging 537 contaminants in wastewaters and the environment: current knowledge, 538 understudied areas and recommendations for future monitoring. Water Res. 72, 3-539 27. 540 Rauf, N., Tahir, S.S., Kang, J-H., Chang, Y-S., 2012. Equilibrium, thermodynamics and 541 kinetics studies for the removal of alpha and beta endosulfan by adsorption onto 542 bentonite clay, Chem. Eng. J. 192, 369–376. 543 Rodríguez-Narváez, O.M., Peralta-Hernandez, J.M., Goonetilleke, A., Bandala, E.R., 544 2017. Treatment technologies for emerging contaminants in water: A review. 545 Chem. Eng. J. 323, 361–380. 546 Sánchez Martín, M.J., Sánchez Camazano, M., Hernández, M.T., Dominguez-Gil, A., 547 1981. Interaction of propranolol hydrochloride with montmorillonite. J. Pharm. 548 Pharmacol. 33(6), 408-410. 549 Sannino, F., Violante, A., Gianfreda, L., 1997. Adsorption-desorption of 2,4-D by 550 hydroxy aluminium montmorillonite complexes. Pestic. Sci. 51 (4), 429-435. 551 Santos, L.H.M.L.M., Gros, M., Rodriguez-Mozaz, S., Delerue-Matos, C., Pena, A., 552 Barceló, D., Montenegro, C.B.S.M., 2013. Contribution of hospital effluents to 553 the load of pharmaceuticals in urban wastewaters: Identification of ecologically 554 relevant pharmaceuticals. Sci. Total Environ. 461–462, 302–316. 555 Singh, N.B., Nagpal, G., Agrawal, S., Rachna., 2018. Water purification by using 556 Adsorbents: A Review. Environ. Technol. Innov. 11, 187-240. 557 24 Smoluchowski, R., 1941. Anisotropy of the electronic work funtion of metals. Phys. 558 Rev. 60, 661–674. 559 Soni, H., 2014. Martindale: the complete drug reference. Emerg. Nurse. 22 (5), 12. 560 Stanley, J.K., Ramirez, A.J., Mottaleb, M., Chambliss, C.K., Brooks, B.W., 2006. 561 Enantiospecific toxicity of the b-blocker propranolol to Daphnia magna and 562 Pimephales promelas. Environ. Toxicol. Chem. 25, 1780–1786.󳮁 563 Tarpani, R.R.Z., Azapagic, A., 2018. Life cycle environmental impacts of advanced 564 wastewater treatment techniques for removal of pharmaceuticals and personal 565 care products (PPCPs). J. Environ. Manag. 215, 258-272. 566 Ullah, H., Wahid, F., Santos, H.A., Khan, T. 2016. Advances in biomedical 567 and pharmaceutical applications of functional bacterial cellulose-based 568 nanocomposites. Carb. Pol. 150, 330-352. 569 Young, R.A. (Ed.), 1993. The Rietveld Method; IUCr Monographs on Crystallography 570 No 5. Oxford University Press, New York. 571 572 573 FIGURE CAPTION 574 Figure 1. Experimental diffractograms obtained for Mt (black) and Mt after the 575 adsorption assay of propranolol (red). 576 Figure 2. Thermal gravimetric analysis ((a) TG (b) DSC) before and after adsorption of 577 propranolol onto Mt. 578 Figure 3. (a) Propranolol adsorption vs. equilibrium concentration, and (b) percentage 579 of propranolol adsorption vs. initial concentration. 580 Figure 4. Langmuir, Freundlich and DR models of propranolol adsorption on Mt. 581 Figure 5. Kinetic models of propranolol adsorption on Mt. 582 25 Figure 6. Effect of pH on propranolol adsorption on Mt. 583 584 585 0 20 40 60 80 100 0.5 1 10 20 40 80 % Adsorbed Ci (mg/L) 0.E+00 5.E+04 1.E+05 0 20 40 60 80 100 120 q (µmol/g) Ce (µmol/L) 1 E+05 5 E+04 0 E+00 Figure Click here to download Figure: Revised Figure 3.pdf R² = 0.99729 -8 -6 -4 -2 0 0.0E+00 1.0E+09 2.0E+09 ln (q (mol/g)) ε2 Dubinin-Raduskevich R² = 0.99322 6 8 10 12 -4 -2 0 2 4 6 ln (q (µmol/g)) ln (Ce (µmol/L)) Freundlich R² = 0.97737 0.E+00 5.E-04 1.E-03 2.E-03 0 20 40 60 80 100 120 Ce/q (g/L) Ce (µmol/L) Langmuir 2 E-03 1 E-03 5 E-04 0 E+00 0 E+00 1 E+09 2 E+09 Figure Click here to download Figure: Revised Figure 4.pdf R² = 0.90534 -5 -4 -3 -2 0 1 2 3 4 5 6 ln(qe-qt) Time (min) Pseudo first order R² = 1.0000 0 0.1 0.2 0.3 0.4 0.5 0.6 0 1 2 3 4 5 6 t/qt (min·g/µmol) Time (min) Pseudo second order R² = 0.9837 8.78 8.80 8.82 8.84 8.86 -3.0 -2.0 -1.0 0.0 1.0 2.0 qt (µmol/g) ln t Elovich model R² = 0.8898 8.78 8.80 8.82 8.84 8.86 0 1 2 3 qt (µmol/g) t1/2 (min1/2) Intra-particle difussion model 0 2 4 6 8 10 0 2000 4000 6000 8000 10000 12000 qt (µmol/g) Time (min) Figure Click here to download Figure: Revised Figure 5.pdf 0 20 40 60 80 100 0 2 4 6 8 10 12 14 % Adsorbed pH Figure Click here to download Figure: Revised Figure 6.pdf