Modified polymer membranes for the removal of pharmaceutical active compounds in wastewater and its mechanism-A review

ABSTRACT

Membrane technology can play a suitable role in removing pharmaceutical active compounds since it requires low energy and simple operation. Even though membrane technology has progressed for wastewater applications nowadays, modifying membranes to achieve the strong desired membrane performance is still needed. Thus, this study overviews a comprehensive insight into the application of modified polymer membranes to remove pharmaceutical active compounds from wastewater. Biotoxicity of pharmaceutical active compounds is first prescribed to gain deep insight into how membranes can remove pharmaceutical active compounds from wastewater. Then, the behavior of the diffusion mechanism can be concisely determined using mass transfer factor model that represented by β and B with value up to 2.004 g h mg⁻¹ and 1.833 mg g⁻¹ for organic compounds including pharmaceutical active compounds. The model refers to the adsorption of solute to attach onto acceptor sites of the membrane surface, external mass transport of solute materials from the bulk liquid to the membrane surface, and internal mass transfer to diffuse a solute toward acceptor sites of the membrane surface with evidenced up to 0.999. Different pharmaceutical compounds have different solubility and relates to the membrane hydrophilicity properties and mechanisms. Ultimately, challenges and future recommendations have been presented to view the future need to enhance membrane performance regarding fouling mitigation and recovering compounds. Afterwards, the discussion of this study is projected to play a critical role in advance of better-quality membrane technologies for removing pharmaceutical active compounds from wastewater in an eco-friendly strategy and without damaging the ecosystem.

Keywords:

• Membrane technology
• biopolymer
• synthetic polymer
• modified membrane
• pharmaceutical active compounds
• pharmaceutical wastewater
• amoxicillin
• paracetamol
• estrogen

1.0 Introduction

The pharmaceutical industry has many effluents that contain antibiotic drugs, antipyretic drugs, analgesic drugs, and synthetic hormones contaminants [1]. The growing pharmaceutical industry at 5.8% since 2017 is a line with the demand for enhancing the quality of human life [2]. Instead of fulfilling human needs, effluent discharge causes environmental and health problems for non-targeting organisms [3]. Several potential issues caused by pharmaceutical effluent contamination are resistance genes for antibiotics, carcinogens, cancer, mutagen, teratogen, higher anti-oxidant response, abnormalities, and mortalities of organisms and allergic reactions for humans [4; 5]. Even antibiotic drugs, antipyretic drugs, analgesic drugs, and synthetic hormones such as amoxicillin, paracetamol, and several types of synthetic estrogens are easy to be degraded, their existence in the waters because of pharmaceutical wastewater has not been given much attention, and many countries still do not have standard medication disposal, such as Brazil [6], East African [7], and Malaysia [8]. However, since the pharmaceutical effluent is quite different from the rest of the conventional effluents, there is a need to remove the pharmaceutical active compounds from wastewater before discharging [9].

Polymer membrane technology is one of the alternative techniques to meet desirable discharge that has been instigated globally [10]. Even though several challenges need to be solved for utilizing polymer membranes to remove the pharmaceutical active compounds from wastewater, polymer membrane is the potential to be developed further by their modification [11]. In addition, several advantages can be obtained by employing a polymer membrane to eliminate pharmaceutical active compounds from wastewater and minimize the compounds contained in effluent. These advantages include its flexibility, chemical and mechanical properties, ease of fabrication, and, last but not least, its reasonable cost [12]. Nowadays, non-modified polymer membrane used for removing pharmaceutical active compounds has several limitations, especially their removal efficiencies; modifying the polymer membrane is a promising better alternative to solve this issue. Moreover, modification of the membrane for removing pharmaceutical active compounds will be of great interest since it needs further exploration to achieve the finest modified polymer membrane [13].

The use of modified polymer membranes in the pharmaceutical industry for eliminating pharmaceutical active compounds before discharging has a bright future. It has shown promising removal efficiencies and is easily implementable, cost-effective, and reusable, as shown in several recent studies. Polyvinylidene fluoride (PVDF) can be modified using several nanoparticles including silicon nanoparticles (SiO₂), silver nanoparticles (Ag), titanium nanoparticles (TiO₂), paladium nanoparticles (Pd), and zinc nanoparticles (ZnO). PVDF/SiO₂ and PVDF/Ag-SiO₂ membranes, had been fabricated for eliminating chemical oxygen demand from pharmaceutical wastewater with removal efficiencies 95.2% and 94.5%, which were higher compared to PVDF only (92.1%) [14]. Polymer membrane (polysulfone) decorated 4% wt TiO₂-HAP nanoparticles had been observed eliminating antibiotic drug chloramphenicol, up to 61.59% [15]. A similar study obtained 51% of paracetamol removal percentage for polysulfone decorated 14% wt TiO₂ for a membrane surface area of 80 cm² and 80% for a membrane surface area of 320 cm² [16]. Another study employed Ag and Pd for the fabrication Ag-Pd/PVDF membrane for rejecting carbamazepine, caffeine, sulfamethoxazole, ibuprofen, and naproxen from pharmaceutical active compounds wastewater up to 40% [17]. A study on eliminating ibuprofen also obtained 35.27% of percentage removal by utilizing PVDF-decorated Ag₂CO₃/Ag₂O [18]. Carbon nanotube utilized zeolitic imidazolate framework 8 (CNT@ZIF8) decorating PVDF-co-hexafluoropropylene (PVDF-co-HFP) could remove > 99.4% of antibiotics, for instance, tetracycline and fluoroquinolones [19]. PVDF decorated Fe(III)-TiO₂ has been proven to degrade 69.9% of bisphenol-A (Yang et al., 2021). Cerium fluoride (CeF₃) nanoparticles embedding polysulfone achieved up to 97% of chemical oxygen demand removal from pharmaceutical active compounds wastewater [20]. The presence of CeF₃ on the membrane surface can enhance hydrophilicity and antifouling properties for eliminating contaminants in wastewater. However, these studies indicated that membrane technology can degrade and eliminate contaminants from pharmaceutical wastewater.

It is becoming increasingly clear that many studies are looking into using membrane technology in wastewater. Recently, it has been sought to organize and analyze information systematically through reviews. The following reviews have been produced on the performance of membranes for the treatment of wastewater: metal oxide functionalized ceramic membranes [21], membranes for the removal of emerging contaminants [22], membrane aerated biofilm reactor [23], and carbon nanotubes for the sequestration of pollutants from wastewater [24]. However, reviews need to comprehensively present the application of polymer membranes for treating wastewater, specifically removing pharmaceutical active compounds from wastewater, including membrane modification and the mass transfer mechanism of pharmaceutical active compounds through a modified polymer membrane. As in the case of most inventions and breakthroughs, these advances must be reviewed extensively in a comprehensive format as they will facilitate further refinement. Thus, this article fills a significant void in the literature by providing comprehensive deep insight into pharmaceutical active compounds biotoxicity and the application of modified polymer membranes to eliminate pharmaceutical active compounds from wastewater. It also overviews essential insights into future challenges and recommendations and proposes a mechanism for the mass transfer of pharmaceutical active compounds through modified polymer membranes. In following up on this study, the findings are expected to contribute to developing improved membrane technologies for removing pharmaceutical active compounds from wastewater in an environmentally friendly way without damaging the ecosystem as a consequence of the process.

2.0 Biotoxicity of pharmaceutical active compounds

2.1 Amoxicillin

Amoxicillin, as seen in Figure 1a, is usually used as an antibiotic for treating gastrointestinal health-associated diseases in humans and animals against various bacteria, including gram-negative and gram-positive bacteria. Amoxicillin is an effective treatment for some diseases, and consequently, its consumption and ingestion have increased in recent years. The ingestion of amoxicillin via excretion by up to 85% for human and 75% for the animal after utilized for maintaining human and animal health lead to several negative impacts on the environment, resulting in it being classified as an emerging contaminant [25]. Considering amoxicillin is an emerging contaminant because of its soluble nature in water, it is easy to enter the soil, waterways, and aquatic environments easily through excretion. Even though excretion is the primary source of amoxicillin, several other major sources of amoxicillin, such as effluent discharged by pharmaceutical industrial facilities and hospitals, contribute to it. As a result of the continuous presence of amoxicillin in the environment that has been accumulated from these major sources, there is a tendency for antibiotic-resistance genes, carcinogens, mutagens, and teratogens to emerge, which pose a threat to organisms that are not targeted.

Figure 1. Chemical structure of pharmaceutical active compounds: (a) amoxicillin, (b) paracetamol, and (c) estrogen (17α-ethinylestradiol).

An earlier study has observed that amoxicillin can induce abnormal development in fetal mice and inhibit the function of several organs and systems, such as the reproductive organs, bones, the hippocampal system, and the liver [26]. In a similar study, it was shown to induce hippocampal hypoplasia in the offspring of mice with impaired neuronal synaptic plasticity and a suppressed proliferation of hippocampal neuronal cells [27]. In the aquatic environment, amoxicillin also induces mortality and oxidative stress in Daphnia magna [28], as well as effects on sex ratio and egg-hatching time of the marine copepod Tigriopus fulvus [29]. Aside from these effects, amoxicillin profoundly affects the enzymological, biochemical, and hematological responses in Labeo rohita [30]. It indicated that amoxicillin exposure in fish induces hepatotoxicity, nephrotoxicity, leukocytosis, hematopoiesis, and lymphocytosis, inferring sustained toxic effects over time. As a result of the presence of amoxicillin in soil, the activity of the catalase enzyme in the soil is induced, and this may harm the growth and weight of plants, the root length, and shoot length, and the oxidative stress in the soil, such as Lemna minor [31] and Spirodela polyrhiza [32]. Amoxicillin also acutely inhibits Lactuca sativa seed germination [33]. Relating to fish and plants, amoxicillin can also be acquired indirectly by non-target humans via the food chain, which can accumulate in the human body. There is evidence that antibiotics such as amoxicillin can negatively impact the health of young children, including weight gain, celiac disease, the presence of Escherichia coli, and genes related to antibiotic resistance [34]. Further, it has adverse effects on the human body, resulting in immuno-allergic reactions and other undesirable effects [35].

2.2 Paracetamol

As seen in Figure 1b, paracetamol is categorized as a non-steroidal anti-inflammatory drug generally employed as antipyretic and analgesic compounds to reduce fever and relieve pain such as backache, headaches, migraine, and cephalgia. Paracetamol is regarded as one of the most commonly used drugs in the pharmaceutical industry because it delivers the desired results, and its excretion rate is within 5% without any changes [36]. Along with amoxicillin, it is also known that paracetamol can be found in hospital effluent, wastewater treatment plants, groundwater, surface water, and drinking water. Paracetamol concentrations were found to be as high as 0.042 mg L⁻¹ in the surface water of the Beberibe River in Brazil [37]. As in the Beberibe River, Brazil’s Semiarid Surface Water also contains 533.64 µg L⁻¹ of paracetamol [38]. On the north coast of Java Island, paracetamol levels have been determined to be 610 ng L⁻¹ [39]. A high concentration of paracetamol was found in the influent of the wastewater treatment plant, about 24,000 ng L⁻¹, and in the Zarqa River, about 600 ng L⁻¹ [40]. There is also evidence of paracetamol in a drinking water treatment plant in Spain, with a concentration of 25.6 ng L⁻¹ [41]. Exposure to paracetamol in the environment threatens the organism and leads to several impacts.

Paracetamol exposure in the environment can affect embryonic development, locomotor behavior, biochemical processes, and epigenetic mechanisms in larvae and embryos of Danio rerio [42]. Nostoc muscorum also displayed higher levels of antioxidant enzymes, including superoxide dismutase, catalase, ascorbate peroxidase, glutathione transferase, and glutathione reductase as well as osmolytes (proline) as a result of the increased paracetamol to counteract the oxidative stress [43]. According to the previous study, exposure to paracetamol affected antioxidant response, which was shown to increase glutathione transferase activity, contrary to the increase found in Daphnia longispina, whereas the glutathione transferase activity decreased in Daphnia magna [44]. It has also been reported that paracetamol has adverse effects on Mytilus edulis gonads, where hemocyte infiltration is found to be the most widespread pathology associated with paracetamol [45]. Paracetamol exposure to Rhamdia quelen resulted in genotoxicity in the blood, gills, and posterior kidney at concentrations of 2.5 and 25 ng mL⁻¹, which was confirmed by the presence of genotoxicity in blood and gills [46].

Furthermore, paracetamol exposure led to lethality in Dugesia japonica [47]. However, these studies indicated that paracetamol exposure could highly affect metabolic response in aquatic organisms, suggesting toxic effects in continuous time. Moreover, paracetamol exposure also led to several effects on soil organisms, such as increased hypoactivity (28 days) and burrowing time (96 h) in Hediste diversicolor [48]. Paracetamol increases superoxide dismutase activity in intermediate exposure levels and glutathione peroxidase and glutathione reductase in chronic levels of exposure. In addition, paracetamol exposure to plants, such as Lens culinaris and Pisum sativum, influenced the percentage of chromosomal abnormalities, mitotic index, root growth, and the presence of micronucleus [49]. Relating to the presence of paracetamol in water bodies, drinking water, and soil, paracetamol can be consumed by humans and organisms that are not targeted.

2.3 Estrogen

Estrogen is a female sex hormone mostly used for oral contraceptive consumption to control female fertility related to birth control [50]. There are several types of estrogen, including estrone, 17β-estradiol, 17α-ethinylestradiol, estriol, and diethylstilbestrol. One of the estrogen molecule structures, 17α-ethinylestradiol, is presented in Figure 2c. It is also identified that 17α-ethinylestradiol can be found in wastewater treatment plants, groundwater, surface water, and soil. In wastewater treatment plants of 282 municipal wastewater treatment plants across 29 countries, 17α-ethinylestradiol in influent and effluent is up to 7890 and 549 ng L⁻¹ [51]. Still in wastewater treatment plants also, similarly, a previous study in Macao, China, presented that 17α-ethinylestradiol has been detected up to 0.96 ng g⁻¹ in the wastewater treatment plant, 0.35 ng g⁻¹ dw in the ecological zone, 0.48 ng g⁻¹ dw in Taipa, and 0.38 ng g⁻¹ dw in an industrial area [52]. Other estrogen particulate concentrations, such as estrone, 17β-estradiol, and estriol, were inspected up to 14.4 ng g⁻¹, 16.6 ng g⁻¹, and 37.5 ng g⁻¹ in the SPM of Yangzi River in China [53]. In addition, colloidal bound phases also ranged from 14.6% to 35.5% for estrone, 7.10–39.5% for 17β-estradiol, and 10.9–29.8% for estriol. However, estrogen in the environment post ingestion can lead to undesired effects on organisms and human health, such as inhibiting metabolism and sexual fitness and inducing vitellogenin in male fish since non-target organisms potentially consume it.

Figure 2. Transformation of pharmaceutical active compounds: (a) amoxicillin, (b) paracetamol, and (c) estrogen (17α-ethinylestradiol).

17α-ethinylestradiol exposure in the aquatic environment cause the reduction of zebrafish larvae size by up to 25%, the swimming behavior of zebrafish larvae, changes the gene expression and proliferation cells, changes hair cell regeneration by up to 50%, and disrupts the annual nerve regeneration of the lateral line of zebrafish as well as the peripheral nervous system in zebrafish [54]. 17α-ethinylestradiol exposure also affected Oncorhynchus mykiss gene expression and hepatic vitellogenin [55]. In longer exposure, 17α-ethinylestradiol can decrease values of the swim tunnel respirometry. 17α-ethinylestradiol exposure can worsen the growth and reproduction of C. elegans [56]. Estrogen, not only 17α-ethinylestradiol but also 17β-estradiol, exhibited a U-shape curve for A. clause embryos, a resistant gene that is not sensitive to their exposure, a reproductive ability and prosome length was noted in females raised with 100-gram L⁻¹ of 17α-ethinylestradiol [57]. In addition, higher stress, catalase activity, carboxylesterases activity, metabolic capacity, and cellular damage had been revealed for Mytilus galloprovincialis, which is exposed to the mixture of 17α-ethinylestradiol and salicylic acid, indicating that the potential severe effect will be found for the mixture of estrogens [58]. These studies indicated that estrogen, especially 17α-ethinylestradiol and the mixture of estrogen with another pharmaceutical active compounds, severely impact aquatic organisms’ survival, development, sex ratio, and reproduction.

3.0 Modified polymer membrane for removing pharmaceutical active compounds

Polymer membranes have been widely contributed to removing contaminants from wastewater since there are many benefits to using this material [59]. These benefits include its flexibility, chemical and mechanical properties, ease of fabrication, and, last but not least, its reasonable cost [60]. Moreover, there are several types of polymer membranes, for instance, according to their sources, geometries, morphologies, and pore characteristics [61]. Polymer membrane sources generally differentiate into biopolymer that extracted and processed from natural polymers, such as deoxyribonuclecic acid, ribonucleis acid, and gelatine [62; 63], and synthetic polymer that derived from petroleum oil [64]. According to membrane geometries, there are tubular, flat sheet, hollow fiber, and electrospun nanofiber [65]. According to membrane morphologies, there are symmetric and asymmetric membranes [66]. Symmetric membranes have one layer with uniform properties, while asymmetric membranes have two main layers with diverse properties, such as morphology and permeability. Asymmetric membranes can be differentiated into asymmetric integral membranes and composite membranes. Similar materials produce the top layer of asymmetric integral membranes, while composite membranes have different materials for their dense top layer. In addition, according to pore characteristics, there are porous and non-porous membranes.

Porous membranes are composed of pores ranging from 0.1 to 10 µm in diameter when used for microfiltration and 0.001 to 0.1 µm for ultrafiltration [67]. It is widely appreciated that the mechanism of separation of porous membranes depends on the distribution of pore size and the molecular size of the membrane [68]. The challenge for porous membranes is membrane fouling that causes flux decline over time. Furthermore, chemical and thermal stability plays a role in membrane selectivity and flux [69]. In this case, it is possible to use the porous membrane support underneath, which can provide sufficient mechanical stability, strength, and high permeability by minimizing the barrier of resistance [70]. Compared to porous membranes, non-porous membranes have pores less than 0.001 µm, making them ideal for nanofiltration, reverse osmosis, and molecular separation in gas phase applications. Non-porous membrane separation depends on pressure, concentration, and electrical potential gradient [71].

Furthermore, there is a difference in solubility as well as diffusivity that leads to this phenomenon. Like porous membranes, non-porous membranes have the same challenge of low flux; they are usually made extremely thin and deposited on top of asymmetric membranes [72]. However, above, composite membrane, categorized as a non-porous type, is potentially used for eliminating pharmaceuticals from wastewater that contains amoxicillin, paracetamol, and estrogen compounds.

In attempts to improve membrane performance and desirable characteristics for eliminating amoxicillin, paracetamol, and estrogen compounds from wastewater, several techniques are applied for modifying membranes, including bulk modification, blending modification, and surface modification [73]. The previous studies employed Ag with SiO₂ for grafting polymer membrane surfaces resulting in chemical oxygen demand removal of up to 98.1% from wastewater [74]. Employing the immersion and precipitation method, methylcellulose as a pore-forming agent and activated carbon as an adsorbent were utilized for membrane modification, increasing water permeability by 34% for removing paracetamol. By adding 0.5% of methylcellulose and 2.5% of activated carbon, the porosity and the rejection rate achieved up to 85.38% and 41.57% for 10 ppm of paracetamol. By using the inversion technique, ZnO can be attached to the polyethersulfone resulting in C=C bond breakage and 90.24% of paracetamol degradation for 5 mL concentration and 86.18% for 10 mL concentration that the transformation of paracetamol is possible drawn as seen in Figure 2b [75]. In the sole solution, the nanofiltration NF50 membrane removed 36% of paracetamol at pH 12 and 12.2% at pH 3 [76]. It increased to 37.59% at pH 3 for a mixture of drug solutions containing paracetamol, ibuprofen, and diclofenac. These results indicated that paracetamol can be removed under acidic conditions and has higher removal for a mixture of drug solutions. Another modification membrane study employed 2% wt of SiO₂ for surface coating polyimide membrane to remove 99.9% of paracetamol with 50 ppm of initial paracetamol concentration at natural pharmaceutical [77].

Similarly, 2% wt of SiO₂ was utilized for decorating polysulfone/polyvinylpyrrolidone membrane and reached 79.82% of amoxicillin removal percentage and getting higher up to 89.81% for 4% wt of SiO₂ that its transformation is possible drawn as seen in Figure 2a [78]. As well as SiO₂, TiO₂ can be utilized for modifying several membranes such as polysulfone, PVDF, and PTFE with removal efficiencies of estrogen (17α-ethinylestradiol) up to 96%, 94%, and 92% for 24 h under ultraviolet irradiation [79]. A similarly modified membrane, PVDF-TiO₂, can remove 96% of 17β-estradiol with 6.5% wt TiO₂, so its transformation is possibly drawn as seen in Figure 2c [80]. It indicated that modified polymer membranes have different abilities to eliminate estrogen compounds from wastewater. In addition, in the case of similarly modified membranes, they have a specific ability to remove different types of estrogen. Moreover, it is possible to obtain higher removal efficiencies for eliminating 17β-estradiol using a polysulfone membrane since the highest efficiency of 17α-ethinylestradiol removal was attained by polysulfone compared to PVDF.

Aside from the efficiency, it needs to assess pure water flux and pore size distribution, which are the key factors for porous membranes. Pure water flux of the membrane attained up to 105.1 L m⁻² h⁻¹ for PVDF/TiO₂ at 0.45 wt% from 63.4 L m⁻² h⁻¹ for pristine PVDF [81]. The presence of TiO₂ in the PVDF membrane was well distributed at 0.45 wt% with a pore density of 21.17%. It was relatively higher compared to the non-presence of TiO₂, with a pore density of 15.5%. Higher pure water flux tends to have higher pore density and relatively large pore size. It also increased the porosity by up to 70% and the roughness of the membrane’s upper surface. The contact angle of the PVDF/TiO₂ membrane, prepared by the thermally induced phase separation method, ranged from 105° to 125° and was symmetric, indicating a hydrophobic membrane. Even though nanoparticles can increase the hydrophilicity, the combined materials with nanoparticles and preparation technique also affect hydrophilicity characteristics, such as a dimethyl phthalate as a combined material that is insoluble in water and thermally induced phase separation as a preparation technique. Another study evidenced that polyethyleneimine affected the contact angle characteristics [82]. The presence of polyethyleneimine that was combined with TiO₂ had a contact angle of less than 50°. It remained lower than the sole presence of polyethyleneimine (near 90°) and TiO₂ (near 75°) in the PVDF membrane surface. Furthermore, the stability of the membrane is required to be characterized, such as thermal and mechanical stability. The combination of polyethyleneimine and TiO₂ in the PVDF membrane surface had good mechanical stability since the permeate fluxes (~210 LMH) did not show significant changes in five cycles of utilization.

4.0 Mass transfer mechanism of pharmaceutical active compounds through modified polymer membrane

Modified membranes by coating and depositing particles on the polymer surface layer can improve membrane performance and provide valuable properties [83]. Modified membrane using nanoparticles has been noted as a great strategy to eliminate the pharmaceutical active compounds from wastewater. Numerous nanoparticles have been proposed to be deposited on the membrane surface, such as Ag, Pd, TiO₂, and SiO₂, by coating or grafting technique [84]. Nanoparticles can be applied to modify polymer membranes since they can enhance hydrophilicity, anti-fouling properties, self-cleaning properties, and increase removal percentage [85]. In addition, nanoparticles on the membrane surface yielded contaminants’ resistance and antimicrobial properties [86; 87]. These valuable properties are appropriate to be presented on modified polymer membranes for the degradation and removal process of pharmaceutical active compounds contained in pharmaceutical wastewater that are harmful to human health and the environment.

The ability of modified polymer membranes that employ nanoparticles to cover their surface can be reflected in Figure 3. Modified polymer membrane for eliminating pharmaceutical active compounds from pharmaceutical wastewater has semi-permeable characteristics that allow excess water to leave the membrane while retaining pharmaceutical active compounds on its surface [88]. This separation process correlates to physicochemical properties, including size, charge, solubility, and diffusivity of solutes as well as pore size, pore size distribution, geometry, wettability, hydrophilicity, membrane thickness, and transmembrane pressure [89]. Fundamentally, the separation of the non-porous membrane plays a role in the solution diffusion [90]. The molecular diffusion model can express the transport of particles or solutes through the membrane. Mass transfer through a membrane correlates with the barrier structure of the membrane, causing a solution-diffusion mechanism that refers to the concentration gradient of permeate and driving force. It has been noted that a penetrant molecule adsorbs, dissolves, and diffuses into the upstream side of a membrane (i.e. the high concentration side), moves over the membrane along a concentration gradient, and is ultimately free or desorbs from the downstream side of the membrane, which is the permeate side. The different solubility and diffusivity of the solutes on the membrane surface mainly led to this mechanism.

Figure 3. Mass transfer mechanism of water and pharmaceutical active compounds molecules through membrane surface.

As seen in Figure 2, paracetamol, amoxicillin, and estrogen molecules are retained on the surface of the membrane as well as water molecules pass the membrane via diffusion as a mass transfer mechanism indicating the membrane is permeable for water, while nonpermeable for pharmaceutical active compounds molecules. As a consequence, a pharmaceutical active compound that is retained in the membrane surface is possible to form a cake layer. However, nanoparticles such as TiO₂ and SiO₂ have excellent self-cleaning properties, which can reduce or detach pharmaceutical active compounds particles from the membrane surface [91]. As in the case of particle cakes, detached pharmaceutical active compounds particles on the membrane surface cannot further deepen the polymer membrane. These properties allow the modified polymer membrane to be an excellent semi-permeable membrane that can separate pharmaceutical active compounds from pharmaceutical wastewater. Given this, the membrane properties regarding water permeability, hydrophilicity, contaminant resistance ability, anti-fouling ability, and self-cleaning ability are well thought-out to synthesize and apply modified membranes with barrier structure to eliminate pharmaceutical active compounds from pharmaceutical wastewater.

According to a previous study, the complexity of particle transport can be defined using mass transfer models [92]. There are three determinations regarding the mass transfer mechanism model: global mass transfer, external mass transfer, and internal mass transfer [93]. Determining global mass transfer, external mass transfer, and internal mass transfer prescribes an external factor of mass transport and an internal one, including kinetic mass transport globally [94]. Global mass transfer, external mass transfer, and internal mass transfer reflect three stages of the solute diffusion process onto a non-porous surface. Global mass transfer reflects the factor of total mass transport of material which determines the solute’s adsorption to attach onto the membrane surface’s acceptor sites [95]. External mass transfer expresses the external transport of solute materials from the bulk liquid to the membrane surface. Internal mass transfer manifests a solute’s diffusion toward the membrane surface’s acceptor sites. The correlation of global mass transfer, external mass transfer, and internal mass transfer can be defined mathematically as:

(1) $\left[k_{L}a\right]d=\left[k_{L}a\right]g-\left[k_{L}a\right]f$(1)

where [k_La]d define as the internal mass transfer factor of pharmaceutical active compounds sorption, [k_La]g defines as the global mass transfer factor of pharmaceutical active compounds sorption, and [k_La]f defines as the external mass transfer factor of pharmaceutical active compounds sorption.

(2) $\left[k_{L}a\right]f=\left[k_{L}a\right]g\times e^{-\beta \times ln(q)}$(2)

with

(3) $ln(q)=\frac{1}{\beta }\times ln(t)+B$(3)

and

(4) $B=\frac{ln\left(\left[k_{L}a\right]g\right)-ln\left\{ln\left(\frac{C_0}{C_s}\right)\right\}}{\beta }$(4)

where B and β defines as the potential mass transfer constant correlated with the driving force as well as the intracellular accumulation of mass transfer during the time of adsorption (mg g⁻¹) and the affinity of absorbate-adsorbent (g d mg⁻¹).

Several studies presented that GMT can analyze the accumulation of adsorbate onto adsorbent surface as seen in Table 1. It had been evidenced that the mathematical model of GMT had good fit for understanding the adsorbate movement, such as PO₄^3-, NH₄⁺, Pb²⁺, Mn²⁺, Al³⁺, Cu²⁺, Fe²⁺, Cr(IV), and Hg⁰ ions as well as Remazol Brilliant Blue R and Methyl Orange dyes, onto the acceptor sites of the adsorbents which relates to R² ranged from 0.970 to 0.999. Further, these adsorbates had β value for instance 1.123–1.336 g h mg⁻¹ for PO₄^3-and 1.146–1.686 g h mg⁻¹ for Remazol Brilliant Blue R dye that followed by B value for instance ranged from −9.913 to −4.276 mg g⁻¹ for PO₄^3- and ranged from 0.220 to 1.651 mg g⁻¹ for Remazol Brilliant Blue R dye. According to these studies, GMT is applicable for inorganic and organic compounds including pharmaceutical compounds such as amoxicillin, paracetamol, and estrogen. Therefore, it is possible to apply GMT to analyze the accumulation of pharmaceutical compounds onto membrane that play role as adsorbents.

Table 1. Overview potential mass transfer constant for removing adsorbate.

Adsorbate	Β (g mg^−1)	B (mg g^−1)	R^2	References
PO4^3−	1.123	−4.276	0.986	[96]
PO4^3−	1.158	−4.392	0.978	[97]
PO4^3−	1.336	−9.913	0.988	[98]
NH4^+	1.152	−3.183	0.994	[99]
NH4^+	1.169	−3.408	0.990	[93]
Pb^2+	0.610	−2.883	0.970	[100]
Mn^2+	2.37	−0.53	0.978	[101]
Al^3+	0.104	1.071	0.975	[102]
Fe^2+	0.045	1.069	0.989
Cu^2+	2.007	1.189	0.991	[92]
Fe^2+	1.427	2.169	0.976
Methyl Orange	2.004	1.833	0.983
Remazol Brilliant Blue R	1.686	1.651	0.983
Remazol Brilliant Blue R	1.146	0.220	0.977	[95]
Cr(VI)	0.71	3.95	0.986	[103]
Hg^0	1.011	−1.31	0.999	[104]

5.0 Challenge and future recommendation

The application of polymer membrane technology for pharmaceutical wastewater remains good performance. Nonetheless, earlier studies on polymer membranes suggested that the anti-fouling properties must be considered since particle pore blocking, pore constriction, and cake formation by particles easily block the membrane surface, especially pharmaceutical active compounds [105]. Consequently, numerous studies assessed polymer membrane modification to diminish membrane fouling using grown materials on the membrane surface. Mostly, polymer membrane modification uses the chemical method since it is simple and provides desirable advantages on the membrane surface. By coating or grafting technique, several nanoparticles have been proposed to be deposited on the membrane surface, such as Ag, Pd, TiO₂, and SiO₂ [106; 107]. Their presence on the membrane surface provides membrane fouling mitigation and offers other properties, such as antimicrobial properties [86; 108] and self-cleaning properties [109]. Besides deposited nanoparticles in the membrane surface, using ultraviolet pre-treatment for the membrane before applying it to the separation process is believed to enhance membrane performance regarding fouling mitigation. In addition, as well as membrane modification, pre-treatment techniques as fouling mitigation strategies, for instance, coagulation, electrocoagulation, adsorption, oxidation, filtration, and flocculation, are also effective approaches for lessening membrane fouling by removing foulants and their precursors. A previous study proved that coagulation could reduce fouling resistance, create larger flocs that are possibly eliminated before passing the membrane surface, and increase permeability [110]. This technique can increase removal efficiencies in the range of 17–23% for handling several pharmaceutical active compounds, including mefenamic acid, atenolol, tetracycline, furosemide, atenolol, diclofenac, and ketoprofen. As well as coagulation, electrocoagulation applied in a membrane reactor can enhance nearly 20–30% removal efficiency of ofloxacin and paracetamol [111]. Electrocoagulation can neutralize the solute charge and allow electrochemically adsorb or oxidate the foulants. In addition, the electrochemical technique provides reactive oxygen species that can clean the foulants in in-situ ways and exert repulsive force. Another study combined activated carbon as a pre-treatment or post-treatment technique and a nanofiltration membrane for removing diclofenac, caffeine, and octyl phenol, which achieved more than 95% of removal percentages [112]. It has been noted that the application of activated carbon as a pre-treatment technique remained better than that of activated carbon as a post-treatment technique.

Similarly, a previous study presented that activated carbon as the pre-treatment technique can enhance the removal performance of the membrane by up to 80% compared to non-activated carbon as a pre-treatment technique for eliminating pharmaceutical active compounds that included paracetamol, triamterene, atrazine, nonylphenol, carbamazepine, simazine, Dilantin, and diuron [113]. These pre-treatments can anticipate membrane fouling by eliminating larger particles before the separation process and causing lower flux than non-pre-treatments addition. However, as previously mentioned, the surface of polymer membranes, coated or grafted using nanoparticles such as TiO₂ and SiO₂, is believed to resist membrane fouling by particles and microbes.

As well as the pre-treatment or modification needs to avoid membrane fouling, the cleaning process of polymer membrane surface is still questionable. The cleaning process is required to provide sustainable membrane performance for the period that correlates with regeneration and recyclable properties. Several cleaning strategies have been proposed, including chemical and physical cleaning for removing pharmaceutical active compounds, as foulants, from pharmaceutical wastewater and recovering the foulants for further use [114]. Chemical cleaning employs chemical compounds called alkaline agents, acids agents, and water. Alkaline solutions are particularly beneficial against organic foulants since the alkaline solution can break down the chemical bonds within the foulant, making it easier to remove and recovery the foulants.

It should be noted that strong alkaline compounds such as sodium hypochlorite (NaOCl) are also effective in removing and recovering biofouling from a vessel. In the event of frequent use, however, the membrane layer can also corrode and cause damage to the membrane as well [115]. An acid compound such as vinegar is possible to remove the foulants. Nonetheless, it is still possible to see remnants on the membrane surface and a challenge to recovery the foulants, pharmaceutical active compounds, from membrane surface [116]. Consequently, it also aggravated the scaling of the membrane due to the increased concentrations and temperature polarization effects. It is also possible to remove an adequate portion of the foulant layer with deionized water for water, which can achieve a high recovery of the permeate flux when used properly [117]. The problem is that cleaning with deionized water can cause irreversible surface fouling. For physical cleaning strategies, there are air backwashing, aeration, and water flushing techniques that earlier studies have explored. Air backwashing for cleaning membrane surface requires homogeneous crystallization, meaning it arose in the bulk feed; the flux decrement was steady and started instantly. A previous study showed that air backwashing increased permeate productivity by up to 230% and crystal production by up to 32% [118]. However, air backwashing seemed ineffective since it had no outcome in reducing flux decrement. Another technique is aeration, which can reduce flux by up to 95% [119]. Nonetheless, it is noteworthy that aeration can remove inorganic material, which modifies the membrane surface, indicating a risk to the membrane’s performance. As well as a chemical technique using deionized water, the cleaning membrane using water flushing must frequently be done to prevent critical scaling.

6.0 Conclusion

Membrane technology is the most suitable pharmaceutical wastewater remediation technology due to its low energy requirement and simplicity of operation. Although membrane technology has advanced progress for wastewater application nowadays, there is still a required modification of membranes to attain high-performance membranes. As part of gaining an in-depth insight into membrane applications for removing pharmaceutical active compounds from pharmaceutical wastewater, this prospective review set out to explore the biotoxicity of pharmaceutical active compounds contaminants in pharmaceutical wastewater, the potential membrane modification for eliminating pharmaceutical active compounds contaminants in pharmaceutical wastewater, and the behavior pharmaceutical active compounds as well as diffusion mechanism of how pharmaceutical active compounds can be transferred onto the membrane surface. Furthermore, concisely, the diffusion mechanism is reflected using the mass transfer factor model comprising global mass transfer, external mass transfer, and internal mass transfer index, which refer to the adsorption of solute to attach onto acceptor sites of the membrane surface, external mass transport of solute materials from the bulk liquid to the membrane surface, and internal mass transfer to diffuse a solute toward acceptor sites of the membrane surface. Ultimately, challenges and future recommendations have been presented to understand the further need for enhancing membrane performance and applying modified membranes in the future.

CRediT authorship contribution statement

Anisa Ratnasari: Writing – original draft, review, editing & revising, Conceptualization

Acknowledgments

The author thanks Department of Environmental Engineering in Institut Teknologi Sepuluh Nopember for facilitating this work. A grateful thanks is also extended to the Indonesia Endowment Fund for Education, also known as LPDP (Lembaga Pengelolaan Dana Pendidikan), for supporting the present work. A special thanks is due to Mrs. Suparmi and Mr. Kusnul Yakin for their technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

No data was used for the research described in the article.

Additional information

Funding

This work was supported by Lembaga Pengelolaan Dana Pendidikan (LPDP/Indonesia Endowment Fund for Education) in Indonesia under Grant No. 0003557/TRP/D/8/lpdp2022