1. Introduction

2. Experimental

2.1. Materials

Progesterone and ibuprofen (Figure 1) were obtained respectively from UP John Company (USA) and Hubei Granules-biocause pharmaceutical CO, LTD (china), they were used without further purification.

Insoluble Poly-alpha-gamma-beta-cyclodextrin-chitosan polymer with a molecular weight of 10,000 Da was procured from start-up In-Cyclo^® , Rouen France.

Chitosan with molecular weight of 300 Da is obtained from SIGMA-ALDRICH, it was put to use without further purification. All other reagents were of analytical grade.

Figure 1. Molecular structure of progesterone and ibuprofen drawn with ShemSketch 3 software program.

Figure 1. Molecular structure of progesterone and ibuprofen drawn with ShemSketch 3 software program.

2.7. Adsorption experiments

Adsorption tests are realized with experimental apparatus, with a continuous up flow column (ID 35 mm; height 120 mm), contains 125 cm³ of pharmaceutical solution (Figure 2).

Figure 2. Experimental setup for the pharmaceuticals extractions with cyclodextrin-chitosan polymer in column system.

Figure 2. Experimental setup for the pharmaceuticals extractions with cyclodextrin-chitosan polymer in column system.

Various quantities of our material were introduced in 60 cm³ solutions contain respectively ibuprofen, progesterone and a mixture of two pharmaceuticals (ibuprofen and progesterone), the solution was supplied to the column and circulated at different liquid velocities. Operating parameters (initial concentration, temperature, flow rate, adsorbent amount) were varied according to experiment.

The time-courses of the ibuprofen and progesterone uptake over respectively 6 hours and 2 hours, were followed by determination of the ibuprofen and progesterone concentration, triplicate measurements were carried out for each study, and the mean values are presented, the error found was $\pm 2$.

Stocks solutions of ibuprofen (30 mg/L) and progesterone (20 mg/L), were prepared respectively in deionized water and a mixture of deionized water/ethanol (60ml / 40ml).

The solutions with desired concentrations were prepared by successive dilution of these stocks solutions.

3. Results and discussion

3.1. Characterization

3.1.1. X-ray analysis of cyclodextrin-chitosan polymers

To study the structure of cyclodextrin-chitosan polymer XRD is used, The X-ray diffractometry (XRD) presented in Figure 3 shows one broad peak and absence of diffraction peaks, and these results report the amorphous structure of cyclodextrin-chitosan polymer.

Figure 3. X-ray diffractogram of cyclodextrin-chitosan polymer.

Figure 3. X-ray diffractogram of cyclodextrin-chitosan polymer.

3.1.2. Properties of cyclodextrin-chitosan polymer

The results of swelling capacity (SC), total acidic (TA), molar mass (Mn) and average molar mass (Mw) are reported in Table 1, we note a high swelling capacity of the polymer, and a considerable quantity of total acidic groups.

Table 1. Properties of cyclodextrin-chitosan polymer.

Table 1. Properties of cyclodextrin-chitosan polymer.

Property	SC (%)	TA (mmol/g)	Mn (g/mol)	Mw (g/mol)
P-α-β-γ-CD-chitosan	71.41	9.50	43 000	310 000

3.1.3. Scanning electron microscopy (SEM)

The SEM features (Figure 4) clearly reveal the nature surface of the dry polymer, his structure resembles to a sponge with thick, homogenous and smooth cavities, cyclodextrin-chitosan polymer has a porous structure with mesopores and some nanocavities, these properties let to high swelling capacity of the polymer (Table 1) consequently, its network can be rapidly expanded to permit a fast diffusion for adsorbates into polymer [26].

Figure 4. Features (SEM) of cyclodextrin-chitosan polymer with different magnifications.

Figure 4. Features (SEM) of cyclodextrin-chitosan polymer with different magnifications.

3.2. Removal of pharmaceutical and effect of operators parameters

The effect of different operator parameters was tested for two pharmaceuticals, such as initial pH, ionic strength, temperature, contact time,

The effect of flow rate was tested only with progesterone. The initial concentration was chosen according to the solubility limit of pharmaceuticals in deionized water which is 10 mg/L and 30 mg/L respectively for progesterone and ibuprofen.

3.2.1. Effect of contact time

Figure 5 shows the removal capacity of ibuprofen and progesterone by cyclodextrin-chitosan polymer at initial concentration of 10 mg/L and 30mg/L respectively for progesterone and ibuprofen, the adsorption equilibrium is reached at 180 min in case of progesterone and at 300 min for ibuprofen.

Figure 5. Effect of contact time on pharmaceuticals adsorption onto cyclodextrin-chitosan polymer conditions : flow rate =1.5 l/h, temperature 25 °C, initial concentration of progesterone and ibuprofen respectively 10 ppm and 30 ppm; pH= 2 in case of ibuprofen and pH=7 in case of progesterone.

Figure 5. Effect of contact time on pharmaceuticals adsorption onto cyclodextrin-chitosan polymer conditions : flow rate =1.5 l/h, temperature 25 °C, initial concentration of progesterone and ibuprofen respectively 10 ppm and 30 ppm; pH= 2 in case of ibuprofen and pH=7 in case of progesterone.

3.2.2. Effect of flow rate

The Figure 6 reveals effect of flow rate on progesterone extraction. The increase in flow rate contributes positively to progesterone removal, this fact may be attributed to the increase of transfer solute from bulk solution to solid surface and the decrease of boundary layer depth formed around the solid surface by increasing of cycle number.

Figure 6. Effect of flow rate (F) on progesterone removal, conditions: amount of adsorbent 25 mg, temperature 25 °C, initial concentration of progesterone 10 ppm, pH= 7.

Figure 6. Effect of flow rate (F) on progesterone removal, conditions: amount of adsorbent 25 mg, temperature 25 °C, initial concentration of progesterone 10 ppm, pH= 7.

3.2.3. Effect of initial pH

The effect of initial pH on progesterone and ibuprofen adsorption on cyclodextrin-chitosan polymer is illustrated in Figure 7. The initial pH has a significant role in the uptake of progesterone and ibuprofen.

We note a little Increase of progesterone adsorption with increasing of pH, when the pH is less than 6.5 (the pK_a value of chitosan) the surface of the polymer is charged positively because the amino group available inside the cyclodextrin-chitosan polymer corresponding to chitosan are protonated, for pH high 6.5 the polymer surface is uncharged

which is favorable to the progesterone adsorption because it is a neutral molecule and is undissociated under pH, these results confirm that chitosan available in cyclodextrin-chitosan polymer play a crucial role in progesterone adsorption by forming electrostatic binding between the two species.

The ibuprofen removal decreases with increasing of initial pH, for pH higher than pK_a of the ibuprofen 4.91 [27,28,29,30], the molecule will be deprotonated and it becomes negatively charged and the adsorption decreases due to its negative charge, which is unfavorable for the formation of an inclusion complex with cyclodextrins, and because of electrostatic repulsion with negative charge of acidic groups in cyclodextrin polymer formed in basic pH.

The removal efficiency is recorded at acidic pH, which confirms that the main mechanism of ibuprofen removal is the inclusion complex formation, between ibuprofen and cyclodextrins. Chitosan seems do not have significant role in ibuprofen adsorption.

Figure 7. Effect of pH on pharmaceuticals adsorption, conditions: adsorbent amount = 25 mg, flow rate =3 l/h, temperature 25 °C, initial concentration of progesterone and ibuprofen respectively 10 ppm and 30 ppm.

Figure 7. Effect of pH on pharmaceuticals adsorption, conditions: adsorbent amount = 25 mg, flow rate =3 l/h, temperature 25 °C, initial concentration of progesterone and ibuprofen respectively 10 ppm and 30 ppm.

3.2.4. Effect of ionic strength

The influence of ionic strength on adsorption of the two pharmaceuticals is shown in Figure 8.

In case of progesterone ionic strength seems do not have significant effect (a slight decrease), because it is a neutral molecule.

For ibuprofen the extraction increases with ionic strength, this effect may be attributed to the screen of the negative charge in ibuprofen molecule and the solubility decrease, which is favorable to the formation of electrostatic interactions and inclusion complexes between cyclodextrins and ibuprofen.

3.2.5. Effect of temperature

Removal of progesterone with cyclodextrin-chitosan polymer decreases as temperature increases (Figure 9), the removal amount is maximal at room temperature (20 °C), however, in case of ibuprofen his removal increases with temperature this effect is due to increasing rates of adsorbate intraparticle diffusion into the pores of adsorbent at higher temperature due to the pores expanding of the polymer or creation of new actives sites.

Figure 8. Effect of NaCl concentration on pharmaceuticals removal, conditions: amount of adsorbent = 25 mg, flow rate =3 l/h, temperature 25 °C initial concentration of progesterone and ibuprofen are respectively 10 ppm and 30 ppm, pH =2 in case of ibuprofen and pH= 7 in case of progesterone.

Figure 8. Effect of NaCl concentration on pharmaceuticals removal, conditions: amount of adsorbent = 25 mg, flow rate =3 l/h, temperature 25 °C initial concentration of progesterone and ibuprofen are respectively 10 ppm and 30 ppm, pH =2 in case of ibuprofen and pH= 7 in case of progesterone.

Figure 9. Effect of temperature (T) on pharmaceuticals, conditions: adsorbent amount is 25 mg, flow rate =3 l/h, initial concentration of progesterone and ibuprofen respectively are 10 ppm and 30 ppm, pH =2 in case of ibuprofen and pH= 7 in case of progesterone.

Figure 9. Effect of temperature (T) on pharmaceuticals, conditions: adsorbent amount is 25 mg, flow rate =3 l/h, initial concentration of progesterone and ibuprofen respectively are 10 ppm and 30 ppm, pH =2 in case of ibuprofen and pH= 7 in case of progesterone.

3.3. Thermodynamic study

Thermodynamic parameters are determined such as, entropy (ΔS) and enthalpy (ΔH),. The temperature-dependence of the distribution coefficient, allows deduction of these parameters by plotting of ln(K_d) versus 1/ temperature.

$$\mathrm{K}\mathrm{d}=\frac{{\mathrm{q}}_{\mathrm{e}}}{{\mathrm{C}}_{\mathrm{e}}}$$

(3)

With:

q_e: Adsorbent amount of the solute at equilibrium (mg/g).

C_e : Concentration of the solute at equilibrium (mg/L).

Hence,

$$\mathrm{K}\mathrm{d}=\frac{{\mathrm{C}}_0-{\mathrm{C}}_{\mathrm{e}}}{{\mathrm{C}}_{\mathrm{e}}}\frac{\mathrm{V}}{\mathrm{m}}$$

(4)

C₀: initial concentration of the solute.

The free energy change can be obtained from the following formula:

ΔG = ΔH − T. ΔS

The free energy change can be also expressed as follow:

ΔG = ΔG⁰ + RT lnK_d.

At equilibrium ΔG = 0

ΔG⁰ = −RT lnK_d

In the other hand

ΔG⁰ = ΔH⁰ − T. ΔS⁰

(5)

$$\mathrm{T}\mathrm{h}\mathrm{e}\mathrm{n}\mathrm{l}\mathrm{n}\mathrm{K}\mathrm{d}=\frac{{\mathsf{\Delta }\mathrm{S}}^0}{R}-\frac{{\mathsf{\Delta }\mathrm{H}}^0}{RT}$$

(6)

This is Vant Hoff s’ law.

Figure 10 illustrates ln K_d plotted versus the inverse of absolute temperature (T), the plots are a good linear regression, it lets us to deduct thermodynamic parameters with precision.

The slope A and the intercept B of the resulting straight line can be calculated from the relationship:

A = - ΔH⁰ /R

B = ΔS⁰ /R

These are used for determine enthalpy changes (ΔH⁰) and the entropy changes (ΔS⁰).

Then the free energy changes can be obtained from the equation (5).

The thermodynamic parameters calculated are summarized in Table 2, the positive value of enthalpy for progesterone indicates that adsorption process on cyclodextrin-chitosan polymer is endothermic; the negative value of the enthalpy in case of ibuprofen indicates the exothermic process.

The positives values of the entropy for the two pharmaceuticals show that the adsorbed molecules on the cyclodextrin-chitosan polymer surface are organized in a more random fashion compared to those in the aqueous phase [31].

Table 2. Thermodynamic parameters of ibuprofen and progesterone adsorption on cyclodextrin-chitosan polymer.

Table 2. Thermodynamic parameters of ibuprofen and progesterone adsorption on cyclodextrin-chitosan polymer.

Molecule	C0(mg/l)	T (K°)	ΔH° (J/mol)	ΔS◦ (J∕◦K.mol)
Progesterone	10	296	38.2319	18.5077
		305
		315
		325
Ibuprofen		296
	30	305	-2.7103	4.4770
		315
		325

Figure 10. Vant’Hoff plots of lnK_d versus 1/ T for (a) progesterone, (b) ibuprofen.

Figure 10. Vant’Hoff plots of lnK_d versus 1/ T for (a) progesterone, (b) ibuprofen.

3.4. Adsorption kinetic study

Adsorption kinetic gives information about adsorption quantity and velocityof the adsorption. Pseudo-second and pseudo-first order models, were utilized to study progesterone and ibuprofen adsorption on cyclodextrin-chitosan polymer.

In case of pseudo first order, Lagergren’s rate equation is one of the most utilized to describe the rate of adsorption [32].

$$\frac{{\mathrm{d}\mathrm{q}}_{\mathrm{t}}}{\mathrm{d}\mathrm{t}}=\mathrm{k}1(\mathrm{q}\mathrm{e}–\mathrm{q}\mathrm{t})$$

(7)

k₁ (min⁻¹) is the pseudo first order adsorption rate coefficient.

For the boundary conditions at (t=0, Q_t =0) and (t = t, q_t = q_t ), the integration of the equation (7) gives the equation (8).

ln (q_e – q_t ) = ln q_e – k₁ t

(8)

q_e : amount adsorbed per unit mass at equilibrium;

q_t : amount adsorbed per unit mass at any time t;

The second order kinetic is described by the following equation [29,32]:

$$\frac{{\mathrm{d}\mathrm{q}}_{\mathrm{t}}}{\mathrm{d}\mathrm{t}}=\mathrm{k}2(\mathrm{q}\mathrm{e}-\mathrm{q}\mathrm{t})2$$

(9)

k₂ is the second order rate coefficient.

The integration and application of the boundary conditions (q_t=0 at t=0 and q_t=q_t at t=t) give a linear form (equation 10).

$$\frac{\mathrm{t}}{{\mathrm{q}}_{\mathrm{t}}}=\frac{1}{{\mathrm{k}}_2{\mathrm{q}}_{\mathrm{e}}^2}+\frac{t}{Q_e}$$

(10)

The integral form of the model, represented by the equation (10) predicts that the ratio of the time/adsorbed amount (t/q_t ) should be a linear function of time [32].

The validity of each model could be checked by the linear regression value (correlation coefficient, R²) and a normalized standard deviation Δq (%) which can be obtained by the following equation [32]:

$$\mathsf{\Delta }\mathrm{q}\left(\mathrm{\%}\right)=\sqrt{{\frac{\sum \left[\frac{{\mathrm{q}}_{\mathrm{e}\mathrm{x}\mathrm{p}}-{\mathrm{q}}_{\mathrm{c}\mathrm{a}\mathrm{l}}}{{\mathrm{q}}_{\mathrm{e}\mathrm{x}\mathrm{p}}}\right]}{\mathrm{n}-1}}^2}\times 100$$

(11)

q_exp : the experimental adsorbed amount per adsorbent mass at equilibrium;

q_cal : the calculated adsorbed amount per adsorbent mass at equilibrium;

n is the number of data points.

The regression coefficient (R²) in case pseudo-first order model is 0.856 and 0.672 respectively for progesterone and ibuprofen, results represented in Table 3 and Table 4 show the low regression coefficient (R² ) and the high values of Δq (%) which denote the invalidity of the model.

The pseudo-second order model is substantially applicable for adsorption kinetics of cyclodextrin-chitosan polymer toward ibuprofen and progesterone, because of the low values of Δq and high regression coefficients R² (Figure 11, Table 3 and 4).

The higher goodness of fitting for the pseudo-second order model could be ascribed to the nature of cyclodextrin-chitosan polymer with multiple adsorption sites, which are responsible to different adsorption steps [33]. This model indicates the dependence of the adsorption process on both adsorbent and adsorbate proprieties.

Adsorption phenomena occur in general, in three consecutive stages:

• liquid film diffusion;
• Intraparticle diffusion or pores diffusion;
• Adsorption of the adsorbate molecule at the active sites on the internal surface of the sorbent.

The last stage is very speed. Therefore, the solute adsorption on adsorbent may be governed by film diffusion process and/or intraparticle diffusion [32].

An intraparticle diffusion model proposed by Weber-Morris [32] is expressed as follows:

q_t = k_it^1/2 + C

(12)

q_t (mg/g) : the adsorbed amount at time t (min);

k_i (mg g^-1 min^-1/2) : the intraparticle diffusion rate constant;

C : the intercept.

If the plot of q_t versus t^1/2 is a straight line, the adsorption process follows the intraparticle diffusion model [32].

Using the equation (12), the graph of adsorbed amount (q_t ) versus t^1/2 for intraparticle transport of ibuprofen and progesterone on cyclodextrin-chitosan polymer were drawn (Figure 11). We constate that the plots don’t give a single straight line, they shown a multilinearity which indicated a multi-step process, the initial linear portion for about 45 min and 120 min for respectively progesterone and ibuprofen, are the gradual adsorption stage, this shows the application the intraparticle diffusion model.

The horizontal linear portion representes the system at equilibrium [34].

Because the plots don’t represent a single straight line and they don’t pass by the origin, we may say that intraparticle diffusion is not the stage governing the kinetics [32].

The liquid film diffusion model is represented by the following equation :

ln(1−F) = −k_fd t

(13)

F is the fractional attainment of equilibrium it equals q_t/q_e,and k_fd (min⁻¹) is the film diffusion rate coefficient.

If the plot of −ln (1−F) versus time t is straight line with zero intercept, we can say that the film diffusion through the liquid film controls the adsorption process [32].

The ibuprofen and progesteroneadsorption on cyclodextrin-chitosan polymer is also not governed by film diffusion, because the plots (plots not showed) have not zero intercept, for this the film diffusion is not the rate-determining step.

Kinetics of ibuprofen and progesterone adsorption is also studied by testing the Elovich model, for this model the solid surface of the adsorbent is energetically heterogenous, and the interaction between the adsorbates molecules don’t affect the adsorption kenitic [32].

The Elovich Equation [32] has been used in the form:

$$\frac{{\mathrm{d}\mathrm{q}}_{\mathrm{t}}}{\mathrm{d}\mathrm{t}}=\mathsf{\alpha }\mathrm{e}\mathrm{x}\mathrm{p}(-\mathsf{\beta }\mathrm{q}\mathrm{t})$$

(14)

α and β are the Elovich coefficient,.

The linear form of the equation (14) is given by [31]:

q_t= β ln (αβ) +β ln t

(15)

The high values of regressions coefficients (R²) and the low values of Δq (%) for the two pharmaceuticals indicate that Elivoch equation is applicable for adsoption kinetics modelling of progesterone and ibuprofen, this is shown respectively in Table 3 and 4.

Table 3. Results of R², k and Δq (%) for different equations used to model the kinetic extraction of progesterone by cyclodextrin-chitosan polymer. .

Table 3. Results of R², k and Δq (%) for different equations used to model the kinetic extraction of progesterone by cyclodextrin-chitosan polymer. .

Equation	(8)	(10)	(12)	(13)	(15)
R2	0.856	0.9998	0.856	0.963	0.932
k (g mg-1min-1)	-	0.0020	-	-	-
Δq (%)	95.08	0.52	41.26	-	9.53

Table 4. Results of R², k and Δq (%) for different equations used to model the kinetic extraction of ibuprofen by cyclodextrin-chitosan polymer.

Table 4. Results of R², k and Δq (%) for different equations used to model the kinetic extraction of ibuprofen by cyclodextrin-chitosan polymer.

Equation	(8)	(10)	(12)	(13)	(15)
R2	0.692	0.9997	0.7270	0.6920	0.8300
k (g mg-1min-1)	-	0.0003	-	-	-
Δq (%)	85.87	5.94	-	-	8.91

Figure 11. Curve-fitting plot of (a1) and (a2) pseudo-second order model for adsorption kinetics respectively of progesterone and ibuprofen, progesterone (b1) and ibuprofen (b2) Curve-fitting plot of intraparticle model.

Figure 11. Curve-fitting plot of (a1) and (a2) pseudo-second order model for adsorption kinetics respectively of progesterone and ibuprofen, progesterone (b1) and ibuprofen (b2) Curve-fitting plot of intraparticle model.

3.5. Comparison between cyclodextrin polymer, cyclodextrin-chitosan polymer and chitosan for removal of pharmaceuticals

A comparison between cyclodextrin polymer, cyclodextrin-chitosan polymer and chitosan alone for extraction of pharmaceuticals was done and presented in Figure 12. It is clear that extraction of progesterone by cyclodextrin polymer and chitosan alone give the same results but it decreases when the cyclodextrins are polymerized with chitosan, this association gives an antagonistic effect.

For ibuprofen, his extraction with cyclodextrin polymer is better than in case of chitosan used alone and it is improved when the cyclodextrin and chitosan are polymerized together, the association of the two gives a synergic effect.

Figure 12. Comparison between cyclodextrins-chitosan and chitosan alone for extraction of ibuprofen and progesterone, amount of adsorbent = 25 mg, flow rate =3 l/h, temperature 25 °C initial concentration of progesterone and ibuprofen are respectively 10 ppm and 30 ppm, pH =2 in case of ibuprofen and pH= 7 in case of progesterone.

Figure 12. Comparison between cyclodextrins-chitosan and chitosan alone for extraction of ibuprofen and progesterone, amount of adsorbent = 25 mg, flow rate =3 l/h, temperature 25 °C initial concentration of progesterone and ibuprofen are respectively 10 ppm and 30 ppm, pH =2 in case of ibuprofen and pH= 7 in case of progesterone.

3.6. Removal of a mixture of two pharmaceuticals (progesterone and ibuprofen)

In a real effluent, we find never one molecule alone, but they exist in a mixture of several molecules, for this we have investigated the removal of mixture of progesterone and ibuprofen with cyclodextrins-chitosan polymer, when they are presented alone and/or in a mixture of two pharmaceuticals.

The results reported in a Figure 13 reveal that the removal of the two pharmaceuticals is unchanged when they are alone or in a mixture, cyclodextrins-chitosan polymer is able to absorb the two molecules with the same yield.

Figure 13. Removal of ibuprofen and progesterone alone and in a mixture of the two pharmaceuticals, amount of adsorbent = 25 mg, flow rate =3 l/h, temperature 25 °C initial concentration of progesterone and ibuprofen are respectively 10 ppm and 30 ppm, pH = 2 in case of ibuprofen and pH= 7 in case of progesterone.

Figure 13. Removal of ibuprofen and progesterone alone and in a mixture of the two pharmaceuticals, amount of adsorbent = 25 mg, flow rate =3 l/h, temperature 25 °C initial concentration of progesterone and ibuprofen are respectively 10 ppm and 30 ppm, pH = 2 in case of ibuprofen and pH= 7 in case of progesterone.

3.7. Physico-chemical methods

3.7.1. X-ray powder diffractometry (XRPD)

Cyclodextrins-chitosan polymer is amorphous, while ibuprofen and progesterone exhibited a series of intense and sharp peaks which shows its crystalline nature (Figure 14).

The cyclodextrins-chitosan polymer, shows the same amorphous structure after extraction of progesterone and ibuprofen, the absence of diffraction peaks of progesterone and ibuprofen in diffractogram of cyclodextrin-chitosan after extraction, may be due to the formation of a less organized system indicating the formation of a real amorphous inclusion complex between pharmaceuticals and cyclodextrins, presented in the cyclodextrins-chitosan polymer, similar results were found in literature [35,36].

This effect can be also due to a mono-molecular dispersion of progesterone and ibuprofen molecules into the polymeric cyclodextrins-chitosan polymers matrix for physical adsorption [37].

Figure 14. X-ray diffractogram of (a) ibuprofen, (b) progesterone and cyclodextrins-chitosan polymers before and after extraction.

Figure 14. X-ray diffractogram of (a) ibuprofen, (b) progesterone and cyclodextrins-chitosan polymers before and after extraction.

3.7.2. Differential scanning calorimetry (DSC)

The results of differential scanning calorimetry analysis of ibuprofen, progesterone and cyclodextrin-chitosan polymer after and before extraction of pharmaceuticals are shown in Figure 15.

Ibuprofen and progesterone thermograms exhibited endothermic peaks respectively at 81.33 °C and 133°C, corresponding to the melting points, while the cyclodextrin-chitosan polymer exhibited a broad endothermic peak corresponding to loss of crystal water containing in the polymer.

The change of endothermic peak in cyclodextrin-chitosan polymer, and the absence of the endothermic peak, corresponding to the melting point of ibuprofen and progesterone in the cyclodextrin-chitosan polymer after extraction, may be due to the interaction of pharmaceuticals with polymer, essentially the formation of inclusion complexes between solute and cyclodextrins containing in polymer and the formation of electrostatic interactions in the network of the polymer.

Figure 15. Differencial scanning calorimetry (DSC) of Ibuprofen, Progesterone cyclodextrin-chitosan polymer after and before extraction of ibuprofen and progesterone, (a) cyclodextrin-chitosan polymer after and before removal of ibuprofen, (b) cyclodextrin-chitosan polymer after and before removal of progesterone.

Figure 15. Differencial scanning calorimetry (DSC) of Ibuprofen, Progesterone cyclodextrin-chitosan polymer after and before extraction of ibuprofen and progesterone, (a) cyclodextrin-chitosan polymer after and before removal of ibuprofen, (b) cyclodextrin-chitosan polymer after and before removal of progesterone.

3.7.3. Regeneration of cyclodextrin-chitosan polymer

Cyclodextrin-chitosan polymer is regenerated after progesterone adsorption with a mixture of water/ethanol with respectively the following proportion (70/30), but in case of ibuprofen it was regenerated with distilled water at pH 9, the number of the regeneration cycles (adsorption and desorption) is presented in Figure 16, which is investigated with progesterone, after twenty three cycles the removal efficiently remains constant.

Figure 16. Cycle of adsorption – desorption of chitosan-cyclodextrin polymer.

Figure 16. Cycle of adsorption – desorption of chitosan-cyclodextrin polymer.

4. Conclusions

References

1. Vinay, K., Sivarama Krishna, L., Neha S., Pritha, C., Mridul U., Ritu P., Jithin, T., Vishal, U. K., Iyyappan, J., Mukesh Kumar, A., Theerthankar, D., Akeem Adeyemi, O., Damia, B., Ludovic, F. D., A critical assessment of technical advances in pharmaceutical removal from wastewater – A critical review, Case. Studies Chem. Environ. Eng., 2023, 8-100363.
2. Tetiana, T., Liubov S., Wojciech, M., Magnetic adsorbents for removal of pharmaceuticals: A review of adsorption properties, J. Mol. Liq., 2023, 384-122174.
3. Reoyo-Prats, B., Hammadi, M., Kim Lai, S., Goetz, V., Calas-Blanchard, C., Joannis-Cassan, C., Plantard, G., Implementation of an advanced photooxidation process to intensify pharmaceuticals removal by a membrane bioreactor, Chem. Eng. Process: Process Intensif., 2023, 191-109460.
4. Koyuncu, I.; Arikan, O. A.; Wiesner, M. R.; Rice, C. Removal of hormones and antibiotics by nanofiltration membranes, J. Membr., 2008, Sci. 309, 94–101. [CrossRef]
5. Yoon, Y.; Westerhoff, P.; Snyder, S. A.; Wert, E. C.; Yoon, J. Removal of endocrine disrupting compounds and pharmaceuticals by nanofiltration and ultrafiltration membranes. Desalination 2007, 202, 16–23. [Google Scholar] [CrossRef]
6. Broséus, R.; Vincent, S.; Aboulfadl, K.; Daneshvar, A.; Sauvé, S.; Barbeau, B.; Prévost, M. ; Ozone oxidation of pharmaceuticals, endocrine disruptors and pesticides during drinking water treatment. water res 2009, 43, 4707–4717. [Google Scholar] [CrossRef]
7. Banasiak, L. J.; Schäfer, A. I. Sorption of steroidal hormones by electrodialysis membranes. J Membr. Sci. 2010, 365, 198–205. [Google Scholar] [CrossRef]
8. Suarez, S.; Lema, J. M.; Omil, F. Pre-treatment of hospital wastewater by coagulation–flocculation and flotation, Bioresor. Technol. 2009, 100 2138–2146. [CrossRef]
9. Oughlis-Hammache. F; Skiba. M; Hallouard. F, Moulahcene.L; Kebiche-Senhadji. O; Benamor. M and Lahiani-Skiba. M, Synthesis and characterization of poly(vinyl-alcohol)-poly(ß-cyclodextrin) copolymer membranes for aniline extraction, Membr. Water Treat., 2016, Vol. 7, No. 3, 223-240.
10. Li, X., Lei, S., Wu, G., Yu, Q., Xu, K., Ren, H., Wang, Y., Geng, J., Prediction of pharmaceuticals removal in activated sludge system under different operational parameters using an extended ASM-PhACs model, Sci. Total Environ., 2023, 871-162065.
11. Adham, S. A. S.; Redding, A. M.; Cannon, F. S.; DeCarolis, J.; Oppenheimer, J.; Werta, E. C.; Yoon, Y. Role of membranes and activated carbon in the removal of endocrine disruptors and pharmaceuticals. Desalination 2007, 202, 156–181. [Google Scholar] [CrossRef]
12. Chen, Q.; Zhang, R.; Wang, J.; Li, L.; Guo, X. Spherical particles of α-, β- and γ-cyclodextrin polymers and their capability for phenol removal, Mater Lett. 2012, 79, 156–158. [Google Scholar] [CrossRef]
13. Bhaskar, M.; Aruna, P.; Jeevan, R.; Jeevan, G.; Radhakrishnan, G. β-cyclodextrin-polyurethane polymer as solid phase extraction material for the analysis of carcinogenic aromatic amines. Anal Chim. Acta. 2004, 509, 39–45. [Google Scholar] [CrossRef]
14. Zhao, D.; Zhao, L.; Zhu, C.; Tian, Z.; Shen, X. synthesis and properties of water-insoluble polymer crosslinked by citric acid with PEG-400 as modifier. Carbohydr Polym. 2009, 78, 125–130. [Google Scholar] [CrossRef]
15. Skiba, M.; Lahiani-Skiba, M. Novel method for preparation of cyclodextrin polymers: physico-chemical characterization and cytotoxicity, J Incl Phenom Macrocycl Chem, 2012. [CrossRef]
16. Moulahcene, L., Skiba, M., Milon, N., Hammache, F., Bounoure, F. and Lahiani-Skiba, M., Removal Efficiency of Insoluble ß-Cyclodextrin Polymer from Water–Soluble Carcinogenic Direct Azo Dyes, Polymers 2023, 15, 732.
17. Ozmen, E. Y.; Yilmaz, M. Use of β-cyclodextrin and starch based polymers for sorption of congo red from aqueous solutions, J. Hazard. Mater., 2007, 148, 303-310. [CrossRef]
18. Moulahcene. L; Skiba. M, Senhadji.O; Milon. N; M. Benamor. M, Lahiani-Skiba. M, Inclusion and removal of pharmaceutical residues from aqueous solution using water-insoluble cyclodextrin polymers, Chem. Eng. Res. Des., 2015, 97, 145–158.
19. Moulahcene. L; Senhadji. O; Skiba. M; Milon. N; Benamor. M ; Lahiani-Skiba. M, Cyclodextrin polymers for ibuprofen extraction in aqueous solution: recovery, separation, and characterization, Desalination Water Treat, 2015, 1–11. [CrossRef]
20. Zhou, L.; Xu, J.; Liang, X.; Liu, Z. Adsorption of platinum (IV) and palladium(II) from aqueous solution by magnetic cross-linking chitosan nanoparticles modified with ethylenediamine. J Hazard. Mater. 2010, 182, 518–524. [Google Scholar] [CrossRef] [PubMed]
21. Rêgo, T.V.; Cadaval Jr, T.R.S.; Dotto, G.L.; Pinto, L.A.A. Statistical optimization, interaction analysis and desorption studies for the azo dyes adsorption onto chitosan films. J Colloid Interface Sci. 2013, 411, 27–33. [Google Scholar] [CrossRef] [PubMed]
22. Chai, K.; Ji, H. Dual functional adsorption of benzoic acid from wastewater by biological-based chitosan grafted β-cyclodextrin. Chem Eng. j., 2012, 203, 309–318. [Google Scholar] [CrossRef]
23. X-Yi, H.; Jian-Ping, B.; Huai-Tian, B.; Gang-Biao, J.; Ming-Hua, Z. Removal of anionic dye eosin Y from aqueous solution using ethylenediamine modified chitosan. Carbohydr polym. 2011, 84, 1350–1356. [Google Scholar]
24. Kyzas G., Z.; Lazaridis N., K.; Bikiaris D., N. Optimisation of chitosan and β-cyclodextrin moleculary imprinted polymer synthesis for dye adsorption. Carbohydr polym. 2013, 91, 198–208. [Google Scholar] [CrossRef] [PubMed]
25. Liu Y.; Cao X.; Hua R.; Wang Y.; Liu Y.; Pang C.; Wang Y.; Selective adsorption of uranyl ion on ion-imprinted chitosan/PVA cross-linked hydrogel, Hydrometallurgy, 2010, 104, 150–155.
26. Li, N.; Wei, X.; Mei, Z.; Xiong, X.; Chen, S.; Ye, M.; Ding, S. synthesis and characterization of a novel polyamidoamine-cyclodextrin crosslinked copolymer. Carbohydr Res. 2011, 346, 1721–1727. [Google Scholar] [CrossRef] [PubMed]
27. Lindqvist, N.; Tuhkanen, T.; Kronberg, L. Occurrence of acidic pharmaceuticals in raw and treated sewages and in receiving waters. Water Res 2005, 39, 2219–28. [Google Scholar] [CrossRef] [PubMed]
28. M. Skiba, Patent PCT-FR 2010 000875, Method for synthesizing calixaren and/or cyclodextrin copolymers, terpolymers and tetrapolymers, 2010.
29. Boukhris T.; Lahiani-Skiba M., Martin D.; Skiba M.; Pre-formulation of an oral cyclosporine free of surfactant, J Incl Phenom Macrocycl Chem, 2012. [CrossRef]
30. Mestre, A.S.; Pires, J.; Nogueira, J.M.F.; Carvalho, A.P. Activated carbons for the adsorption of ibuprofen, Carbon 45 (2007) 1979–1988. [CrossRef]
31. Purkait, M.K.; Maiti, A.; DasGupta, S.; De, S. Removal of congo red using activated carbon and its regeneration. J Hazard. Mater. 2007, 145, 287–295. [Google Scholar] [CrossRef] [PubMed]
32. Sen Gupta, S.; Bhattacharyya, K. G. Kinetics of adsorption of metal ions on inorganic materials: A review. Adv Colloid Interface Sci. 2011, 162, 39–58. [Google Scholar] [CrossRef] [PubMed]
33. Liu, H.; Cai, X.; Wanga, Y.; Chen, J. Adsorption mechanism-based screening of cyclodextrin polymers for adsorption and separation of pesticides from water, water Res. 2011, 45, 3499 -3511. [CrossRef]
34. Li, N.; Mei, Z.; Wei, X. Study on sorption of chlorophenols from aqueous solutions by an insoluble copolymer containing β-cyclodextrin and polyamidoamine units. Chem Eng. J. 2012, 192, 138–145. [Google Scholar] [CrossRef]
35. Hirlekar, R.; Kadam, V. Preparation and characterization of inclusion complexes of carvedilol with methyl-β-cyclodextrin. J Incl. Phenom. Macrocycl. Chem. 2009, 63, 219–224. [Google Scholar] [CrossRef]
36. Ribeiro, A.; Figueiras, A.; Santos, D.; Veiga, F. Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-β-cyclodextrin, AAPS Pharm- SciTech. 2008, 9, 1102–1109. [CrossRef]
37. Mura, P.; Faucci, M.T.; Maestrelli, F.; Furlanetto, S.; Pinzauti, S. Characterization of physicochemical properties of naproxen systems with amorphous β-cyclodextrin-epichlorohydrin Polymers. J Pharm. Biomed. Anal. 2002, 29, 1015–1024. [Google Scholar] [CrossRef] [PubMed]