Sorption Potential of Different Forms of TiO 2 for the Removal of Two Anticancer Drugs from Water

: Anticancer drugs pose a potential risk to the environment due to their signiﬁcant consumption and biological effect even at low concentrations. They can leach into soils and sediments, wastewater, and eventually into drinking water supplies. Many conventional technologies with more effective advanced oxidation processes such as photocatalysis are being extensively studied to ﬁnd an economical and environmentally friendly solution for the removal of impurities from wastewater as the main source of these pharmaceuticals. Since it is impossible to treat water by photocatalysis if there is no sorption of a contaminant on the photocatalyst, this work investigated the amount of imatinib and crizotinib sorbed from an aqueous medium to different forms of photocatalyst. In addition, based on the sorption afﬁnity studied, the applicability of sorption as a simpler and less costly process was tested in general as a potential route to remove imatinib and crizotinib from water. Their sorption possibility was investigated determining the maximum of sorption, inﬂuence of pH, ionic strength, temperature, and sorbent dosage in form of the suspension and immobilized on the ﬁberglass mesh with only TiO 2 and in combination with TiO 2 /carbon nanotubes. The sorption isotherm data ﬁtted well the linear, Freundlich, and Langmuir model for both pharmaceuticals. An increasing trend of sorption coefﬁcients K d was observed in the pH range of 5–9 with CRZ, showing higher sorption afﬁnity to all TiO 2 forms, which was supported by K F values higher than 116 ( µ g/g)(mL/ µ g) 1/n . The results also show a positive correlation between K d and temperature as well as sorbent dosage for both pharmaceuticals, while CRZ sorbed less at higher salt concentration. The kinetic data were best described with a pseudo-second-order model ( R 2 > 0.995).


Introduction
Environmental pollution is a ubiquitous problem that humanity has been dealing with for many years. When considering the impact of various factors on the environment, more and more attention is paid to pharmaceuticals. These are biologically active compounds used to treat and prevent diseases, alleviate of symptoms, etc., in human and veterinary medicine [1,2]. The modernization of technology and science has led to the promotion of quality of life through the increased production of medicines whose consumption is increasing every day [3]. Since information about their fate is still limited and there are no environmental laws, they can reach different sources in the environment and undergo processes, such as sorption, photolysis, hydrolysis or even biodegradation. These processes can often produce transformation or degradation products that are more toxic than the Table 1. Physicochemical properties of pharmaceuticals [14,26,27].

Chemicals and Reagents
The studied pharmaceuticals imatinib (IMT) and crizotinib (CRZ) with high purity were supplied by Pliva. Table 1 shows the structures of the active ingredients and their physicochemical properties. NaOH (p.a.) was purchased from Gram-mol, Zagreb, Croatia. HCl was purchased from VWR Chemicals, SAD, NaCl from Lach Ner, Czech Republic, acetonitrile from J. T. Baker, Netherlands, and formic acid from T.T.T. d.o.o., Sv. Nedjelja, Croatia. The standard stock solution (1000 mg/L) of IMT was prepared by dissolving a precisely weighed amount of the powder in MilliQ water while CRZ was dissolved in acetonitrile. The working standard solutions (5; 10; 15; 20; 25 mg/L) were prepared by diluting the standard solution of pharmaceuticals in MilliQ water. HCl and NaOH were used to adjust the pH. In the experiments in which the influence of ionic strength was studied, the working standard solutions were prepared using NaCl (0.001; 0.01 and 0.1 M) instead of water.

Sorbent Preparation and Characterization
Titanium dioxide (TiO2) was supplied by Evonik (Aeroxide ® , TiO2 P25 with a crystalline content of 75% anatase and 25% rutile), and the multi-walled carbon nanotubes (CNT) were obtained from Chengdu Organic Chem. Co. (outside diameter from 5 nm to 30 nm, purity > 95% and length from 10 μm to 30 μm). The suspension was prepared by weighing 0.01 g TiO2 in 10 mL of pharmaceutical aqueous solution. Before immobilization of the catalyst to the support, glass fiber (GF) meshes were cut and adapted to the dimensions of the glass vessels with an average area of 10.17 cm 2 . The procedure for solgel preparation and characterization of two types of immobilized photocatalysts (TiO2-GF and TiO2/CNT-GF) on a round-cut glass fiber mesh was the same as described in previously published papers [28,29]. The average weight of the immobilized TiO2 film was 0.0037 g/cm 2 and 0.072 g/cm 2 for TiO2/CNT, respectively. Adding such a mesh to a drug volume of 10 mL yielded an average concentration of 3.76 g/L. Analogous to the above calculations, the concentration of TiO2/CNT-GF mesh was 73.2 g/L, higher than that of TiO2-GF at the beginning, so it is expected that sorption will be higher with this type of catalyst.
In order to get insight in sorbent, clean GF mesh, pure TiO2, mesh with TiO2-GF and TiO2/CNT-GF were recorded by a scanning electron microscope (SEM-QUANTA FEG-250, Zaragoza, Spain) operated at 20 kV. Figure 1 shows SEM images and by comparing the surfaces of TiO2 (b) and TiO2 after binding to glass fibers (c), it can be seen that agglomeration has occurred. Furthermore, TiO2/CNT-GF (d) bonds noticeably produce even larger agglomerates. As it is well known, (I) the surface plays an important role in

Chemicals and Reagents
The studied pharmaceuticals imatinib (IMT) and crizotinib (CRZ) with high purity were supplied by Pliva. Table 1 shows the structures of the active ingredients and their physicochemical properties. NaOH (p.a.) was purchased from Gram-mol, Zagreb, Croatia. HCl was purchased from VWR Chemicals, SAD, NaCl from Lach Ner, Czech Republic, acetonitrile from J. T. Baker, Netherlands, and formic acid from T.T.T. d.o.o., Sv. Nedjelja, Croatia. The standard stock solution (1000 mg/L) of IMT was prepared by dissolving a precisely weighed amount of the powder in MilliQ water while CRZ was dissolved in acetonitrile. The working standard solutions (5; 10; 15; 20; 25 mg/L) were prepared by diluting the standard solution of pharmaceuticals in MilliQ water. HCl and NaOH were used to adjust the pH. In the experiments in which the influence of ionic strength was studied, the working standard solutions were prepared using NaCl (0.001; 0.01 and 0.1 M) instead of water.

Sorbent Preparation and Characterization
Titanium dioxide (TiO2) was supplied by Evonik (Aeroxide ® , TiO2 P25 with a crystalline content of 75% anatase and 25% rutile), and the multi-walled carbon nanotubes (CNT) were obtained from Chengdu Organic Chem. Co. (outside diameter from 5 nm to 30 nm, purity > 95% and length from 10 μm to 30 μm). The suspension was prepared by weighing 0.01 g TiO2 in 10 mL of pharmaceutical aqueous solution. Before immobilization of the catalyst to the support, glass fiber (GF) meshes were cut and adapted to the dimensions of the glass vessels with an average area of 10.17 cm 2 . The procedure for solgel preparation and characterization of two types of immobilized photocatalysts (TiO2-GF and TiO2/CNT-GF) on a round-cut glass fiber mesh was the same as described in previously published papers [28,29]. The average weight of the immobilized TiO2 film was 0.0037 g/cm 2 and 0.072 g/cm 2 for TiO2/CNT, respectively. Adding such a mesh to a drug volume of 10 mL yielded an average concentration of 3.76 g/L. Analogous to the above calculations, the concentration of TiO2/CNT-GF mesh was 73.2 g/L, higher than that of TiO2-GF at the beginning, so it is expected that sorption will be higher with this type of catalyst.
In order to get insight in sorbent, clean GF mesh, pure TiO2, mesh with TiO2-GF and TiO2/CNT-GF were recorded by a scanning electron microscope (SEM-QUANTA FEG-250, Zaragoza, Spain) operated at 20 kV. Figure 1 shows SEM images and by comparing the surfaces of TiO2 (b) and TiO2 after binding to glass fibers (c), it can be seen that agglomeration has occurred. Furthermore, TiO2/CNT-GF (d) bonds noticeably produce even larger agglomerates. As it is well known, (I) the surface plays an important role in The standard stock solution (1000 mg/L) of IMT was prepared by dissolving a precisely weighed amount of the powder in MilliQ water while CRZ was dissolved in acetonitrile. The working standard solutions (5; 10; 15; 20; 25 mg/L) were prepared by diluting the standard solution of pharmaceuticals in MilliQ water. HCl and NaOH were used to adjust the pH. In the experiments in which the influence of ionic strength was studied, the working standard solutions were prepared using NaCl (0.001; 0.01 and 0.1 M) instead of water.

Sorbent Preparation and Characterization
Titanium dioxide (TiO 2 ) was supplied by Evonik (Aeroxide ® , TiO 2 P25 with a crystalline content of 75% anatase and 25% rutile), and the multi-walled carbon nanotubes (CNT) were obtained from Chengdu Organic Chem. Co. (outside diameter from 5 nm to 30 nm, purity > 95% and length from 10 µm to 30 µm). The suspension was prepared by weighing 0.01 g TiO 2 in 10 mL of pharmaceutical aqueous solution. Before immobilization of the catalyst to the support, glass fiber (GF) meshes were cut and adapted to the dimensions of the glass vessels with an average area of 10.17 cm 2 . The procedure for sol-gel preparation and characterization of two types of immobilized photocatalysts (TiO 2 -GF and TiO 2 /CNT-GF) on a round-cut glass fiber mesh was the same as described in previously published papers [28,29]. The average weight of the immobilized TiO 2 film was 0.0037 g/cm 2 and 0.072 g/cm 2 for TiO 2 /CNT, respectively. Adding such a mesh to a drug volume of 10 mL yielded an average concentration of 3.76 g/L. Analogous to the above calculations, the concentration of TiO 2 /CNT-GF mesh was 73.2 g/L, higher than that of TiO 2 -GF at the beginning, so it is expected that sorption will be higher with this type of catalyst.
In order to get insight in sorbent, clean GF mesh, pure TiO 2 , mesh with TiO 2 -GF and TiO 2 /CNT-GF were recorded by a scanning electron microscope (SEM-QUANTA FEG-250, Zaragoza, Spain) operated at 20 kV. Figure 1 shows SEM images and by comparing the surfaces of TiO 2 (b) and TiO 2 after binding to glass fibers (c), it can be seen that agglomeration has occurred. Furthermore, TiO 2 /CNT-GF (d) bonds noticeably produce even larger agglomerates. As it is well known, (I) the surface plays an important role in the sorption process, and (II) the agglomeration reduces the surface area. These are important facts in this paper. sorption process, and (II) the agglomeration reduces the surface area. These are important facts in this paper.

Sorbent Studies
Batch sorption experiments were performed in glass vessels by shaking in a laboratory shaker (Innova 4080 Incubator Shaker, New Brunswick Scientific, Minneapolis, MN, USA) that allowed continuous contact (200 rpm) between a specific type of TiO2 and 10 mL of aqueous IMT/CRZ solution. After shaking, the solutions were centrifuged and filtered through 0.20-µ m membrane syringe filters (Scheme 1). To determine the time required to reach sorption equilibrium, initial experiments were performed by shaking 5, 15, and 25 mg/L IMT/CRZ solution with TiO2 at 25 °C for various time periods (10,20,30,40,50,60,120,240,360,1080, and 1440 min). Based on these experiments, a contact time of 24 h was sufficient to establish equilibrium between

Sorbent Studies
Batch sorption experiments were performed in glass vessels by shaking in a laboratory shaker (Innova 4080 Incubator Shaker, New Brunswick Scientific, Minneapolis, MN, USA) that allowed continuous contact (200 rpm) between a specific type of TiO 2 and 10 mL of aqueous IMT/CRZ solution. After shaking, the solutions were centrifuged and filtered through 0.20-µm membrane syringe filters (Scheme 1). sorption process, and (II) the agglomeration reduces the surface area. These are important facts in this paper.

Sorbent Studies
Batch sorption experiments were performed in glass vessels by shaking in a laboratory shaker (Innova 4080 Incubator Shaker, New Brunswick Scientific, Minneapolis, MN, USA) that allowed continuous contact (200 rpm) between a specific type of TiO2 and 10 mL of aqueous IMT/CRZ solution. After shaking, the solutions were centrifuged and filtered through 0.20-µ m membrane syringe filters (Scheme 1). To determine the time required to reach sorption equilibrium, initial experiments were performed by shaking 5, 15, and 25 mg/L IMT/CRZ solution with TiO2 at 25 °C for various time periods (10,20,30,40,50,60,120,240,360,1080, and 1440 min). Based on these experiments, a contact time of 24 h was sufficient to establish equilibrium between To determine the time required to reach sorption equilibrium, initial experiments were performed by shaking 5, 15, and 25 mg/L IMT/CRZ solution with TiO 2 at 25 • C for various time periods (10,20,30,40,50,60, 120, 240, 360, 1080, and 1440 min). Based on these experiments, a contact time of 24 h was sufficient to establish equilibrium between IMT/CRZ and TiO 2 suspension and CRZ sorbed onto TiO 2 /CNT, while other forms of immobilized TiO 2 on fiber glass mesh were agitated for 4 h.
Five concentration levels were used (5; 10; 15; 20; 25 mg/L) for the isotherm experiments to test the influence of pH, ionic strength, temperature, and sorbent dosage. The initial pH was adjusted to pH 7 prior to each of the aforementioned experiments, except for the pH influence where pH values 3, 5, 9, and 11 were also tested. All experiments were performed in duplicate.

Instrumental Procedure
IMT and CRZ samples were analyzed with the HPLC-DAD, Agilent 1100 System (Santa Clara, CA, USA) using Kinetex C18 stationary phase (150 × 4.6 mm, particle size 3.5 µm). The mobile phase with a flow rate of 0.5 mL/min consisted of 0.1% formic acid in Mili-Q water (eluent A) and 0.1% formic acid in acetonitrile (eluent B). Gradient elution began with 80% of eluent A. Within the next 6 min, the composition of eluent A decreased to 20%. After holding 20% of A for 1 min, the initial phase composition was returned and maintained for 7 min. The injection volume was 25 µL. Detection was monitored at 258 nm for IMT and 270 nm for CRZ, respectively.

Data Anaylsis
Sorption isotherms are models that predict the nature and mechanism of interaction between sorbates and sorbent. The obtained sorption data were analyzed using the linear and two-parameter models: Freundlich and Langmuir isotherms. The isotherm constants were obtained by linearizing the model using linear regression as the simplest method for data analysis.
Through the linear model, the sorption coefficient K d is expressed as the ratio between the amount of drug in the sorbent (q e , mg/g) and the solution (C e , mg/L) [30]: The empirical Langmuir model (2) was used to describe whether the sorption process is a homogenous process that forms in a monolayer on a fixed number of active sites with no interactions between the sorbed molecules. It is given in a linear form [31]: where q m (mg/g) and K L (L/mg) represent the maximum sorption capacity (mg/g) and the equilibrium constant referred to sorption energy and the affinity between TiO 2 and pharmaceuticals. Calculating R L , a dimensionless constant, the nature of sorption can be inferred; R L values above 1 indicate an unfavorable process, whereas sorption is favored at R L between 0 and 1 [32]. The Freundlich isotherm can be applied to describe the sorption equilibrium for heterogeneous surfaces with possibility of multilayer formation, where all sorption from all sites occurs at the point with the highest binding energy [31,33].
K F is the Freundlich constant indicating the relative sorption capacity ((µg/g) (mL/µg) 1/n ) and 1/n is the heterogeneity parameter which indicates the sorption intensity with values ranging from 0 to 1 [34]. Values above 1 indicate cooperative sorption, while lower values than 1 are caused by chemisorption [35].

Sorption Kinetic Models
The Lagergren's pseudo-first kinetic model (Equation (4)), Ho's pseudo-second kinetic model (Equation (5)), and Weber and Morris intraparticle diffusion model (Equation (6)) were used to evaluate the mechanism and describe the phases of the sorption process.
q t and q e represent the amount of sorbed analyte at time t and at equilibrium state (µg/g), k 1 is the constant rate of pseudo-first-order (min −1 ), k 2 is the constant rate of pseudosecond-order kinetic model (g/µg min), while k id is the intraparticle diffusion rate constant (µg/g min 1/2 ) [33]. The sorption process can be described by a few stages. The first stage involves the transfer of sorbate near the surface of the sorbent. The second stage is called external diffusion followed by intraparticle diffusion as the third stage. The last stage includes chemical and physical reactions on the surface of the sorbent [36].

Kinetic Study
The maximum time required to reach sorption equilibrium was examined by shaking pharmaceutical solutions with three initial pharmaceutical concentrations (5, 15, and 25 mg/L) for 11 different time periods. The TiO 2 suspension reached equilibrium with both pharmaceuticals after 24 h. IMT and CRZ were not significantly sorbed on immobilized TiO 2 after 4 h, whereas CRZ was required to remain in contact with TiO 2 /CNT-GF for 24 h. Review of the literature revealed similar results for multi-walled CNTs as sorbents in the case of sulfapyridine and sulfamethoxazole, which also reached equilibrium after 4 h, while ciprofloxacin moved even longer than CRZ (72 h) [21,37]. For all three types of sorbents, sorption in the initial phase is a dominant and fast process, while sorption after reaching equilibrium was a slow process over time. The initial concentrations did not affect the contact time between pharmaceutical and TiO 2 . Tables 2 and 3 show the parameters from the kinetic study in which the pseudo-firstand pseudo-second-order models were tested for IMT and CRZ, respectively. For the pseudo-first-order model, the linear correlation coefficient R 2 does not show good agreement, while the R 2 for pseudo-second-order kinetic model was very high (R 2 > 0.99). The theoretical values q e,cal were closer to the experimental values q e,exp obtained at all concentrations used. Thus, the pseudo-second-order model is the better model for describing the sorption kinetics of the two pharmaceuticals on all three types of TiO 2 photocatalyst.
The intraparticle diffusion constants obtained and values related to the boundary layer thickness indicate that the sorption process occurs mainly in three stages. After contact with an aqueous solution of pharmaceutical and the solid phase, the compound migrates into the sorbent boundary layer. The second stage involves intraparticle diffusion between the porous material and the IMT/CRZ. Sorption at the active sites of the sorbents and equilibrium state are usually reached in the third stage, which is confirmed by the smallest slope, k p3 (Tables 4 and 5) [33,38]. This step is very fast and does not control the rate of the whole sorption process. From the obtained results, it can be concluded that the sorption of IMT and CRZ on TiO 2 samples is a complex process controlled mainly by external and intraparticle diffusion. The C values increased from the first to the third stage, with values greater than 0 confirming the first step of surface sorption as the rate-limiting step [39].

Modeling of Sorption Isotherms-Influence of pH
The sorption parameters of the three types of sorbents fitted to the linear, Freundlich, and Langmuir isotherms are shown in Table 6 for IMT and Table 7 for CRZ, respectively. The linear isotherm showed the best fit to the obtained data for all TiO 2 experiments at different pH values (R 2 > 0.99) suggesting the domination of partition interactions [40]. The sorption coefficient K d showed an increasing trend with increasing pH values for IMT and CRZ on TiO 2 in three forms (Figure 2). According to the literature [41,42], the zeta potential of TiO 2 is between 6 and 6.5, so TiO 2 is positively charged at pH 5; it is probably predominantly negatively charged at pH 7 and 9. The pK a value of IMT nitrogen atom of piperazine is about 7.8-8.07 [27,43], which means that IMT is positively charged in acidic medium and predominantly negatively charged under alkaline conditions. At pH 5, electrostatic repulsive interactions predominated causing the least sorption, while at higher pH values, electrostatic attractive forces were promoted between neutral IMT and more negatively charged TiO 2 . At pH 9, the sorption affinity of the pharmaceutical was highest, while at pH 7 (value close to the isoelectric point of the sorbent), agglomeration was possible on the TiO 2 surface resulting in lower sorption affinity [41,44]. A similar trend in sorption affinity was obtained with CRZ which has two pK a values: 5.6 and 9.4. It can exist in positive, neutral, and negative forms under different pH conditions [26]. Therefore, the increase in sorption coefficient is accompanied by an increase in pH, which is due to the different species present in the medium causing repulsive forces at pH 5 or attractive forces at pH 9. It has been shown that the efficiency of drug removal can be strongly influenced by the presence of different ionizable species of the drug by changing the process conditions, i.e., sorption can be positively influenced by an increase in pH as in this study or negatively influenced in the case of ciprofloxacin and multi-walled CNT (above pH 7) [37], and cefdinir in the pH range of 4-10 using TiO 2 as a sorbent [45].
Appl. Sci. 2022, 12, x FOR PEER REVIEW 9 of 15 medium and predominantly negatively charged under alkaline conditions. At pH 5, electrostatic repulsive interactions predominated causing the least sorption, while at higher pH values, electrostatic attractive forces were promoted between neutral IMT and more negatively charged TiO2. At pH 9, the sorption affinity of the pharmaceutical was highest, while at pH 7 (value close to the isoelectric point of the sorbent), agglomeration was possible on the TiO2 surface resulting in lower sorption affinity [41,44]. A similar trend in sorption affinity was obtained with CRZ which has two pKa values: 5.6 and 9.4. It can exist in positive, neutral, and negative forms under different pH conditions [26]. Therefore, the increase in sorption coefficient is accompanied by an increase in pH, which is due to the different species present in the medium causing repulsive forces at pH 5 or attractive forces at pH 9. It has been shown that the efficiency of drug removal can be strongly influenced by the presence of different ionizable species of the drug by changing the process conditions, i.e., sorption can be positively influenced by an increase in pH as in this study or negatively influenced in the case of ciprofloxacin and multi-walled CNT (above pH 7) [37], and cefdinir in the pH range of 4-10 using TiO2 as a sorbent [45]. To investigate the sorption capacity and multilayer formation on heterogeneous surfaces, the parameters n and KF were calculated from the logarithmic form of the Freundlich isotherm [46,47]. In the case of sorption of both pharmaceuticals to TiO2 in suspension, the n values are higher than 1, indicating that this type of sorbent is favorable for the removal of IMT and CRZ at low concentrations [48,49]. The sorption of IMT on TiO2-GF mesh is described by n close to 1 (at pH 5 and 9), confirming the linearity of the isotherm and the constant affinity for sorption in the applied concentration range. At the surface of TiO2/CNT-GF, sorption was a cooperative process with the same n values for each pH showing the decrease in affinity of IMT sorption due to the filled active binding sites [50]. CRZ showed a constant sorption potential with higher sorbate concentration on both immobilized catalysts with n values close to unity. The sorption capacity coefficients KF were highest for the suspension, confirming the highest affinity for sorption of IMT in this form.
Other KF values are relatively low (19.3-27.2 (μg/g)(mL/μg) 1/n ), indicating the mobility of pharmaceutical in the sorbent [51]. CRZ generally showed higher tendency to sorb to all TiO2 forms. The Langmuir model in conjunction with the Freundlich isotherm also fitted the experimental data very well, as in the case of cefdinir and TiO2 suspension [45], indicating the complexity of sorption considered as a possible monolayer, and heterogenous multilayer process [45,48,52]. At pH 9, the highest values of maximum saturated monolayer sorption capacity qm (except for immobilized TiO2 at pH 7) of the three TiO2 modifications were obtained, indicating a higher sorption capacity at the mentioned pH, which is in agreement with the determined Kd values. In general, the TiO2 suspension showed To investigate the sorption capacity and multilayer formation on heterogeneous surfaces, the parameters n and K F were calculated from the logarithmic form of the Freundlich isotherm [46,47]. In the case of sorption of both pharmaceuticals to TiO 2 in suspension, the n values are higher than 1, indicating that this type of sorbent is favorable for the removal of IMT and CRZ at low concentrations [48,49]. The sorption of IMT on TiO 2 -GF mesh is described by n close to 1 (at pH 5 and 9), confirming the linearity of the isotherm and the constant affinity for sorption in the applied concentration range. At the surface of TiO 2 /CNT-GF, sorption was a cooperative process with the same n values for each pH showing the decrease in affinity of IMT sorption due to the filled active binding sites [50]. CRZ showed a constant sorption potential with higher sorbate concentration on both immobilized catalysts with n values close to unity. The sorption capacity coefficients K F were highest for the suspension, confirming the highest affinity for sorption of IMT in this form. Other K F values are relatively low (19.3-27.2 (µg/g)(mL/µg) 1/n ), indicating the mobility of pharmaceutical in the sorbent [51]. CRZ generally showed higher tendency to sorb to all TiO 2 forms. The Langmuir model in conjunction with the Freundlich isotherm also fitted the experimental data very well, as in the case of cefdinir and TiO 2 suspension [45], indicating the complexity of sorption considered as a possible monolayer, and heterogenous multilayer process [45,48,52]. At pH 9, the highest values of maximum saturated monolayer sorption capacity q m (except for immobilized TiO 2 at pH 7) of the three TiO 2 modifications were obtained, indicating a higher sorption capacity at the mentioned pH, which is in agreement with the determined K d values. In general, the TiO 2 suspension showed the better capacity to sorb both pharmaceuticals, which was expected due to the higher number of active sites on the catalyst surface and easier mass transfer while immobilization of material by trapping active sites may decrease the surface activity [22]. Higher mass of TiO 2 does not necessarily bring higher sorption performance, rather the performance of the sorbent or catalyst plays a major role. The results are also consistent with the results of the SEM analysis (Figure 1), which shows the agglomeration occurred during the binding of TiO 2 and TiO 2 /CNT to GF meshes, resulting in a decrease in the active surface area of the sorbent. However, to avoid problems in sample reuse and filtration, it is better to immobilize only TiO 2 and not to use it in combination with nanotubes because the different active sites of the two materials may cause heterogeneous sorption [45].

Influence of Ionic Strength
Standard solutions of pharmaceuticals at a natural pH 7 were prepared in the presence of 0.001 M, 0.01 M, and 0.1 M NaCl instead of MilliQ water to determine the sorption capacity by changing the concentration of the inorganic salt.
A slight increasing trend of IMT sorption with higher ionic strength for all three sorbent samples (Figure 3) can be attributed to possible neutralization of the TiO 2 surface by positive ions, which allows non-electrostatic interactions between pharmaceutical and sorbent [53]. Increased sorption may also be the result of decreased solubility of the pharmaceutical due to addition of soluble salts in aqueous solution [48]. The higher concentration of Na + ions affecting the decrease in CRZ sorption on TiO 2 may be the result of decreased active sites due to competitive sorption between Na + and CRZ, and weak electrostatic repulsion interactions due to equal charges of sorbent and sorbate, including ambient pH [54]. Determining the effect of ionic strength provides important information on how much the removal of organic contaminants from water is affected by the presence or addition of different ions. These results may also indicate that the sorption of IMT and CRZ is also affected by different substances in the water matrix, which needs to be confirmed by additional experiments.
Appl. Sci. 2022, 12, x FOR PEER REVIEW 10 of 15 number of active sites on the catalyst surface and easier mass transfer while immobilization of material by trapping active sites may decrease the surface activity [22]. Higher mass of TiO2 does not necessarily bring higher sorption performance, rather the performance of the sorbent or catalyst plays a major role. The results are also consistent with the results of the SEM analysis (Figure 1), which shows the agglomeration occurred during the binding of TiO2 and TiO2/CNT to GF meshes, resulting in a decrease in the active surface area of the sorbent. However, to avoid problems in sample reuse and filtration, it is better to immobilize only TiO2 and not to use it in combination with nanotubes because the different active sites of the two materials may cause heterogeneous sorption [45].

Influence of Ionic Strength
Standard solutions of pharmaceuticals at a natural pH 7 were prepared in the presence of 0.001 M, 0.01 M, and 0.1 M NaCl instead of MilliQ water to determine the sorption capacity by changing the concentration of the inorganic salt.
A slight increasing trend of IMT sorption with higher ionic strength for all three sorbent samples (Figure 3) can be attributed to possible neutralization of the TiO2 surface by positive ions, which allows non-electrostatic interactions between pharmaceutical and sorbent [53]. Increased sorption may also be the result of decreased solubility of the pharmaceutical due to addition of soluble salts in aqueous solution [48]. The higher concentration of Na + ions affecting the decrease in CRZ sorption on TiO2 may be the result of decreased active sites due to competitive sorption between Na + and CRZ, and weak electrostatic repulsion interactions due to equal charges of sorbent and sorbate, including ambient pH [54]. Determining the effect of ionic strength provides important information on how much the removal of organic contaminants from water is affected by the presence or addition of different ions. These results may also indicate that the sorption of IMT and CRZ is also affected by different substances in the water matrix, which needs to be confirmed by additional experiments.

Effect of Sorbent Dosage
For each type of sorbent, experiments were performed with three different sorbent dosages ( Figure 4); the lower mass and the higher mass of the sorbent used in the experiments described above. The percentage of sorption was not affected too much by higher dosage of sorbent; a slight increase in Kd with higher mass was observed, which was due to an increase in active sites for both types of immobilized TiO2 [55]. When the TiO2 is in the form of a suspension, a linear increase in IMT sorption was observed. A minor influence of sorbent dosage was also observed in the sorption of two sulfonamide antibiotics on multi-walled CNTs, which showed the opposite trend, i.e., a higher mass of sorbent

Effect of Sorbent Dosage
For each type of sorbent, experiments were performed with three different sorbent dosages ( Figure 4); the lower mass and the higher mass of the sorbent used in the experiments described above. The percentage of sorption was not affected too much by higher dosage of sorbent; a slight increase in K d with higher mass was observed, which was due to an increase in active sites for both types of immobilized TiO 2 [55]. When the TiO 2 is in the form of a suspension, a linear increase in IMT sorption was observed. A minor influence of sorbent dosage was also observed in the sorption of two sulfonamide antibiotics on multi-walled CNTs, which showed the opposite trend, i.e., a higher mass of sorbent does not necessarily increase the removal efficiency due to the occurrence of saturation [21,55]. does not necessarily increase the removal efficiency due to the occurrence of saturation [21,55].

Sorption Thermodynamics
To describe the nature of the sorption process by determining thermodynamic parameters, experiments were performed at temperatures of 25, 30, and 35 °C (298; 303; 308 K). The pH of the solutions was adjusted to a neutral environment (pH 7). It was found that temperature has different influences on sorption to TiO2 in different forms ( Table 8). The sorption of IMT on the suspension decreased with increasing temperature. For the sorption of IMT on TiO2-GF, the effect of temperature was not noticeable due to a slight increase in active sites and Kd values. A similar temperature effect was found for the sorption of CRZ on all TiO2 forms; increasing the temperature led to an increase in molecular diffusion to the surface of the photocatalyst and then promoted pharmaceutical binding [56]. Similar sorption thermodynamics depending on the type of sorbent used as for IMT was also reported for ciprofloxacin [37].

Sorption Thermodynamics
To describe the nature of the sorption process by determining thermodynamic parameters, experiments were performed at temperatures of 25, 30, and 35 • C (298; 303; 308 K). The pH of the solutions was adjusted to a neutral environment (pH 7). It was found that temperature has different influences on sorption to TiO 2 in different forms ( Table 8). The sorption of IMT on the suspension decreased with increasing temperature. For the sorption of IMT on TiO 2 -GF, the effect of temperature was not noticeable due to a slight increase in active sites and K d values. A similar temperature effect was found for the sorption of CRZ on all TiO 2 forms; increasing the temperature led to an increase in molecular diffusion to the surface of the photocatalyst and then promoted pharmaceutical binding [56]. Similar sorption thermodynamics depending on the type of sorbent used as for IMT was also reported for ciprofloxacin [37]. Thermodynamic parameters, including Gibbs free energy, ∆G • , enthalpy, ∆H • , and entropy, ∆S • , were calculated using the following equations [57]: The sorption of IMT and CRZ on all sorbents is favorable and spontaneous physisorption process, which is confirmed by negative values of ∆G • , ranging from −1.8 to −14.8 kJ/mol for both pharmaceuticals [58]. The more negative the ∆G • values, the higher sorption affinity of the pharmaceuticals, as a result of increased driving molecular forces such as Van der Waals forces [59]. The positive ∆H • and ∆S • values indicate that the sorption of CRZ onto three forms of TiO 2 and of IMT onto both types of immobilized TiO 2 , is an endothermic reaction [60], where an increase in temperature leads to a higher sorption capacity. Based on the negative values of the thermodynamic parameters ∆H • and ∆S • , it can be assumed that IMT sorption in suspension is an exothermic reaction in which randomness at the interface of TiO 2 and IMT solution decreases [33,59].

Statistical Analysis
Statistical analysis was performed by calculating correlations between the parameters affecting sorption as independent variables (pH, ionic strength, temperature, sorbent dosage) and the dependent one-the sorption coefficient. Pearson's correlation coefficient r can range from −1 to +1, while − or + indicate the direction of correlation [61]. The sorption of IMT to all types of TiO 2 under different influences showed strong linear correlations with r higher than 0.84. A slightly weaker correlation was found for the influence of ionic strength on IMT sorption to TiO 2 -GF ( Figure 5). A similar trend was also observed for CRZ, where a strong positive correlation (r = 0.87-0.98) indicated a proportional relationship between K d and pH, temperature, and sorbent dosage. The sorption of CRZ showed a negative medium-strong correlation when the ionic strength of the solution was changed. The sorption of IMT and CRZ on all sorbents is favorable and spontaneous physisorption process, which is confirmed by negative values of ∆G°, ranging from −1.8 to −14.8 kJ/mol for both pharmaceuticals [58]. The more negative the ∆G° values, the higher sorption affinity of the pharmaceuticals, as a result of increased driving molecular forces such as Van der Waals forces [59]. The positive ∆H° and ∆S° values indicate that the sorption of CRZ onto three forms of TiO2 and of IMT onto both types of immobilized TiO2, is an endothermic reaction [60], where an increase in temperature leads to a higher sorption capacity. Based on the negative values of the thermodynamic parameters ∆H° and ∆S°, it can be assumed that IMT sorption in suspension is an exothermic reaction in which randomness at the interface of TiO2 and IMT solution decreases [33,59].

Statistical Analysis
Statistical analysis was performed by calculating correlations between the parameters affecting sorption as independent variables (pH, ionic strength, temperature, sorbent dosage) and the dependent one-the sorption coefficient. Pearson's correlation coefficient r can range from −1 to +1, while − or + indicate the direction of correlation [61]. The sorption of IMT to all types of TiO2 under different influences showed strong linear correlations with r higher than 0.84. A slightly weaker correlation was found for the influence of ionic strength on IMT sorption to TiO2-GF ( Figure 5). A similar trend was also observed for CRZ, where a strong positive correlation (r = 0.87-0.98) indicated a proportional relationship between Kd and pH, temperature, and sorbent dosage. The sorption of CRZ showed a negative medium-strong correlation when the ionic strength of the solution was changed.

Conclusions
In this manuscript, preliminary data on the removal of IMT and CRZ from an aqueous solution by sorption processes with TiO2 suspension, TiO2-GF, and immobilized TiO2/CNT-GF were presented. The influence of contact time, solution pH, initial pharmaceutical concentration, ionic strength, sorbent dosage, and ambient temperature was studied to determine the affinity of IMT and CRZ for the photocatalyst used. Statistical analysis confirmed that the complexity of the sorption process is strongly influenced by the various parameters mentioned above. Since most of the pharmaceuticals present in the environment are expected to be in ionized form, the experiments were carried out at different pH values in the range of 5-9, to show what interactions may occur due to the physicochemical properties of sorbent and sorbate during the sorption process. The Kd values obtained from the linear isotherm, the best model to describe the sorption processes for both pharmaceuticals (R 2 > 0.99), increased with increasing alkalinity of the aqueous

Conclusions
In this manuscript, preliminary data on the removal of IMT and CRZ from an aqueous solution by sorption processes with TiO 2 suspension, TiO 2 -GF, and immobilized TiO 2 /CNT-GF were presented. The influence of contact time, solution pH, initial pharmaceutical concentration, ionic strength, sorbent dosage, and ambient temperature was studied to determine the affinity of IMT and CRZ for the photocatalyst used. Statistical analysis confirmed that the complexity of the sorption process is strongly influenced by the various parameters mentioned above. Since most of the pharmaceuticals present in the environment are expected to be in ionized form, the experiments were carried out at different pH values in the range of 5-9, to show what interactions may occur due to the physicochemical properties of sorbent and sorbate during the sorption process. The K d values obtained from the linear isotherm, the best model to describe the sorption processes for both pharmaceuticals (R 2 > 0.99), increased with increasing alkalinity of the aqueous medium. When inorganic salt was added to the solution, an opposite behavior of the drugs was observed. The sorption affinity of CRZ decreased with increasing concentration of Na-cations, while IMT was slightly more sorbed on all three catalyst types. Increasing the mass of TiO 2 also increased the active sites on the catalysts, resulting in higher sorption affinity of the two drugs. Thermodynamic parameters indicated spontaneity of CRZ and IMT sorption on all catalyst forms used. Higher ambient temperature had positive effect on the sorption of pharmaceuticals on both types of immobilized TiO 2 and on the suspension for CRZ, while IMT added in suspension showed an exothermic response. The pseudo-second-order model best described the kinetics of the sorption process with R 2 values close to one. Despite the fact that the suspended form of TiO 2 had a higher sorption capacity, when the efficiency of the removal process, sorption or photocatalysis was considered together with the operating costs, including the preparation of the sorbent, it can be concluded that the suspension is not cost-effective in real water treatment applications at higher levels, considering the time-consuming and expensive separation without the possibility of reuse.
CRZ and IMT showed a similar and relatively good tendency to sorb to the TiO 2 photocatalyst, which can be considered for future research as a potential sorbent for pharmaceuticals removal from various types of water matrices. If a compound has a good affinity for the sorption catalyst, the sorption process should be considered as an economically and environmentally efficient method for the removal of contaminants, rather than a process that requires higher energy consumption.