Pharmaceutical residues in aquatic environment and water remediation by TiO₂ heterogeneous photocatalysis: a review

Abstract

The occurrence of pharmaceutical compounds in the natural water sources has been reported as early as in the year 1980. Until now, the presence of pharmaceutical compounds in the aquatic environment has been frequently reported in the literature. Moreover, increasing evidence suggests that these contaminants have posed a threat to both humans and ecosystems. In this regard, the present review paper seeks to offer an overview of this environmental issue of pharmaceutical pollution where the subject matters to be reviewed include the effects, sources and mitigation strategies of pharmaceuticals in the aquatic environment. Besides, a review of the fundamentals and mechanisms of heterogeneous photocatalysis technology is also presented in this paper. Heterogeneous photocatalysis is a rapidly expanding technology which has been extensively investigated and applied in wastewater treatment for the remediation of persistent pollutants such as pharmaceutical compounds during the last decade. Furthermore, the ideal photocatalyst titanium dioxide (TiO₂), which can collaborate and perform well in the photocatalysis treatment process, is also discussed. The advantages and limitations associated with the application of this treatment method are summarized and discussed in details. Finally, this review paper focuses on the future trend of the photocatalysis technology and identifies the barriers and lacking parts which need to be resolved in the near future.

Introduction

Water is one of the important resources on earth where human beings and ecological systems rely on it for survival. If there is no water, there will be no life on earth. Nowadays, the demand of water increases with the rapid growth of population and vigorous industrial development. High-quality water sources are necessary particularly in maintaining healthy ecosystems and assurance for safe drinking water.

Common water pollutants including pesticides, polychlorinated biphenyls (PCBs), poly aromatic hydrocarbons (PAHs), metals such as mercury, lead, cadmium and arsenic, to name a few, have been significantly reduced through the adoption of appropriate legal measures and the removal of numerous dominant pollution sources (Al-Odaini et al. 2013). Recently, the scientific community starts to focus on a new group of pollutants, which are pharmaceuticals (Choina et al. 2013; Doll and Frimmel 2005; Putschew et al. 2000; Ternes 1998). Pharmaceuticals are known as the “new emerging pollutants” since they are recently detected in the environment in increasing amount. Up to now, pharmaceuticals are not covered by regulations, and their effects on the environment and human health are still poorly understood (Quadra et al. 2016; Sangion and Gramatica 2016).

Pharmaceutical is one of the most indispensable elements with undeniable benefits in modern life (Blair 2016; Sangion and Gramatica 2016). They are extensively and increasingly used as an integral component to establish and maintain a healthy population of both humans and livestock (Choina et al. 2013; Mozia and Morawski 2012; Wilkinson et al. 2016). However, due to the widespread application of pharmaceuticals and their inadequate removal from wastewater, low levels of pharmaceuticals (ranging from the low ng/L to mg/L) have been ubiquitously detected (in both original and metabolized forms) in various aquatic compartments such as surface water, groundwater, effluents of sewage treatment plant, seawater (Daughton and Ternes 1999; Halling-Sørensen et al. 1998) and even in the drinking water (Doll and Frimmel 2005; Sacher et al. 2001; Vaizoğullar 2017).

The retained pharmaceuticals in different water sources may lead to some adverse effects on the biological balance and human health such as aquatic toxicity, resistance development in pathogenic bacteria, acute and chronic damage, hormonal and endocrine disruption (Emmanuel et al. 2005; K’oreje et al. 2016; Wu et al. 2012; Yang et al. 2008a). This situation is changing from bad to worse when these persistent pharmaceuticals are unable to be eliminated by using conventional wastewater treatment techniques due to the typical characteristics of the pharmaceuticals (Achilleos et al. 2010; Al-Odaini et al. 2013; Mozia and Morawski 2012). For example, pharmaceuticals are lipophilic to pass membranes and facilitate the absorption. Besides, they can escape from the biological treatment process since they are designed to be biologically active and persistent to maintain their therapeutic activity until the specific physiological function on the human and animals has been performed (Achilleos et al. 2010; Aguilar et al. 2011; Suarez et al. 2009; Zhang et al. 2008). Therefore, they have the properties to bioaccumulate and cause negative effects to aquatic or terrestrial ecosystems, such as immobilization, mortality, inhibition of growth and reproduction (Quadra et al. 2016).

The continuous input and persistence of pharmaceuticals in the aquatic ecosystem indicate an environmental challenge even only at low concentrations. Recently, studies are concerning on the removal of pharmaceuticals during treatment by using heterogeneous photocatalysis wastewater treatment technique (Bahnemann 2004; Lofrano et al. 2009; Sharma et al. 2012). The field of heterogeneous photocatalysis has been expanding rapidly within the last four decades (Ibhadon and Fitzpatrick 2013). Photocatalysis performs the redox function through the transformation, deactivation and, finally, the minimization of environmentally persistent compounds (Aziz et al. 2016).

This review paper aims to give an overview of the occurrence of pharmaceutical compounds in the aquatic environment, including the sources, effects and solutions to overcome the pharmaceutical pollution. Also, the understanding and fundamentals of heterogeneous photocatalytic wastewater treatment technology, including the advantages and limitations of the photocatalysis process, were discussed in details in the review. The last part of this review concerns on the lacking part of current studies and the areas of future research.

Pharmaceuticals in the aquatic environment

The most frequently detected pharmaceuticals in the water sources and their concentrations are summarized in Table 1 (Bagheri et al. 2016; Quadra et al. 2016; Wilkinson et al. 2016). Basically, they are divided into eight main classes based on their specific mode of therapeutic action, namely antibiotic, analgesic and antipyretic, central nervous system (CNS) stimulant, iodinated X-ray contrast media, antidepressant, beta blocker, hormone/steroid and lipid regulator. The presence of pharmaceutical compounds as the new emerging pollutants in the natural water resources is becoming an issue of global concern (Mozia and Morawski 2012; Nasuhoglu et al. 2011; Wu et al. 2012). The main factors concerned relating to this issue are the lack of the baseline data and the malfunctioning of the conventional wastewater treatment methods.

Table 1 Most frequently detected pharmaceuticals in water sources and their concentrations. Data taken from Quadra et al. (2016), Bagheri et al. (2016) and Wilkinson et al. (2016)

Pharmaceutical pollution has not been given a significant attention despite its increased and extensive application for different purposes throughout the world in nowadays (Choina et al. 2013; Mozia and Morawski 2012). Ignorance on this matter is due to the fact that pharmaceuticals are not regulated as environmental pollutants and not listed as pollutants in the WHO guidelines for drinking water quality (Al-Odaini et al. 2013). This, in turn, leads to the lack of baseline data regarding the occurrence of pharmaceutical compounds in the aquatic environment, thus prohibiting the evaluation of public exposure and the subsequent effects (Arpin-Pont et al. 2016; Sim et al. 2011; Taylor and Senac 2014). As the effects on human health are unknown and the findings on the aquatic organisms are limited, the severity of this issue may be covered up and turning to worse as day goes on (Bagheri et al. 2016). Most probably, the hidden effects may slowly accumulate and expose unexpectedly and irreversibly.

Besides, studies have proven that the conventional wastewater treatment plants are unable to eliminate the retained pharmaceutical compounds completely (Achilleos et al. 2010; Cai and Hu 2017; Mozia and Morawski 2012; Zhang et al. 2008). This is because the conventional wastewater treatment plants such as sedimentation and biological treatment process are not designed to remove the persistent pharmaceuticals which are polar, predominantly water soluble in nature, neither volatile nor biodegradable (Aguilar et al. 2011; Al-Odaini et al. 2013; Bagheri et al. 2016; Luo et al. 2015; Maroga Mboula et al. 2012; Palominos et al. 2009). Other treatment methods such as activated carbon adsorption, air stripping and reverse osmosis have also been investigated for the elimination of pharmaceuticals. However, these processes are just transferring the pharmaceutical compounds from one phase to another without eliminating them (Elmolla and Chaudhuri 2010a).

Effects of retained pharmaceuticals

Pharmaceuticals are one of the vital substances which are beneficial to our daily life, particularly in terms of therapy and healthcare facilities. However, when the pharmaceuticals are exposed to the nontarget organisms, the beneficial function may not be performed. In contrary, its biological activity may cause abundant of acute and chronic effects which can adversely affect the wildlife and ecosystem health (Sangion and Gramatica 2016; Wilkinson et al. 2016). In the last three decades, the presence and impact of pharmaceuticals in the environment have gained an increasing concern. Pharmaceuticals, being a large, diverse and persistent group of emerging organic micropollutants, are found to be poorly removed by conventional wastewater treatment processes and thus have been ubiquitously detected in the natural water sources and even drinking water. So far, the retained pharmaceutical compounds in the environment are reported at concentrations ranging from the low ng/L to mg/L (K’oreje et al. 2016). However, it is important to highlight that these pollutants can pose a risk for aquatic life by various mechanisms even at low concentration (Blair 2016; Wu et al. 2012).

Pharmaceutical pollution has been verified to induce the endocrine or hormonal disruption problem, causing the abnormal reproduction of fish (Khataee et al. 2013; Yang et al. 2008a). Kidd et al. (2007), who conducted the experiment in a pristine lake at the Experimental Lakes Area in Canada, has found out that the addition of steroid estrogen ethinyl estradiol (EE2) can lead to the feminization of males as well as the collapse of a fish population. Recently, Sangion and Gramatica (2016) have also reported on the same endocrine disruption problem where the EE2 caused the feminization of male fish in river and water bodies, even at concentrations of few ng/l. In addition, fish with intersex gonads and feminization of males or vice versa have been found in some rivers in the UK. The similar incident occurred in the city of Boulder, Colorado, where the white suckers (a type of fish) also encountered the endocrine disruption problems such as gonadal intersex, disrupted ovarian, reduced gonad size and testicular histopathology. These endocrine disruption problems are caused by the long-term exposure of the aquatic organisms to the estrogenic compounds which are retained in the water sources (Stoner and Kosinski 2008).

Furthermore, pharmaceutical residues in the aquatic environment are reported to have some ecotoxic effects. For example, enrofloxacin and ciprofloxacin (two different types of fluoroquinolone antibiotics) which are frequently detected in wastewater and surface water are toxic to algae (Ebert et al. 2011). Besides, the antibiotic of tetracycline has been proven to bring the toxic effects to the plants and the early stage of aquatic organisms. It also causes the negative impact to the sewage sludge bacteria by inhibiting their protein synthesized process (Yahiat et al. 2011). Moreover, diclofenac is known as the most toxic analgesics in acute exposure studies with the growth inhibition (EC₅₀) below 100 mg/L (Fent et al. 2006). Again, diclofenac and hormones have been shown to bring fatal effects on fish, crustaceans and algae at very low doses (Bagheri et al. 2016). The developed antibiotic resistance by the pathogenic bacteria is also one of the verified adverse effects identified in the previous studies (Elmolla and Chaudhuri 2010b; Maroga Mboula et al. 2012). These developed antibiotic resistance genes which could cause the genotoxic effects to the microorganisms will then spread in the environment and lead to the occurrence of aquatic toxicity (Khataee et al. 2013; Yang et al. 2008a).

Further instances of the effects of different pharmaceutical compounds on the aquatic organisms are summarized in Table 2. Based on Table 2, it is noticeable that the pharmaceuticals can induce some negative impacts to the flora, fauna and microorganisms in the aquatic environment. Although most of the reported half-maximal effective concentrations (EC₅₀) and half-maximal inhibitory concentration (IC₅₀) are found to be higher than those detected in the environment, these results are still concerned due to the possibility of synergistic effects with other pharmaceuticals and more intense effects at long-term exposure (Quadra et al. 2016). For example, research by Cleuvers (2003) has indicated that, in comparison to the singly measured toxicities, mixture of ibuprofen and diclofenac can cause more immobilization in Daphnia magna (microcrustacean) and inhibition of the average growth rate for algae, which clearly demonstrate the synergistic effect of the mixture pharmaceuticals.

Table 2 Review of studies examining the effects of different pharmaceutical compounds on the aquatic organisms

Up to now, concerns still remain regarding the harm of pharmaceutical residues to human health, particularly to a developing fetus (Blair 2016). Somehow, it is suggested that long-term exposure to the retained pharmaceuticals may bring unintended effects to the human health since pharmaceuticals are designed to be highly interactive with the receptors of human and animals (Abellán et al. 2007; Jelić et al. 2012). It is important to highlight that the continuous discharge of pharmaceutical compounds will lead to a higher retained concentration in the future time associated with unpredictable adverse effects on human, aquatic and terrestrial organisms. Hence, further studies are required to acquire more verified adverse effects of the retained pharmaceutical compounds on the living organisms, especially on the human being, so that it can become a convincing fact to alert the society regarding the seriousness of this pharmaceutical pollution.

Major sources of pharmaceuticals

Tons of drugs are produced every year and broadly applied in both human and veterinary medicine (Quadra et al. 2016). More than 200 types of pharmaceutical compounds (mainly painkillers, vascular drugs, antibiotics and antidepressants) are frequently detected in aquatic and terrestrial compartments with the concentration ranging from few ng/l to thousand μg/l (Sangion and Gramatica 2016). Therefore, understanding the sources and fates of pharmaceuticals in the environment is vital for the determination of suitable approaches to prevent them from entering the water supply (Bagheri et al. 2016; Helwig et al. 2016). Pharmaceuticals may reach aquatic ecosystems through many pathways (Quadra et al. 2016). Figure 1 illustrates the possible sources and fates of pharmaceuticals in the environment. Basically, there are four major sources which contribute to the occurrence of pharmaceuticals in the aquatic environment: human use, veterinary use, agriculture and farming use, as well as the industrial production.

Fig. 1

Possible sources and fates of pharmaceuticals in the environment. Adapted and modified from Quadra et al. (2016) and Bagheri et al. (2016)

As shown in Fig. 1, pharmaceuticals can reach the water sources via the emission from healthcare facilities (hospitals and clinics) and households (such as private residences, dormitories, hotels, residential care facilities) (Abellán et al. 2007; Chang et al. 2010; LA Ioannou et al. 2011). Among all, hospitals act as the main source of pharmaceuticals released to the environment particularly through the patients’ excretions (Bagheri et al. 2016; Straub 2016). Following human consumption, excreted residue (feces and urines) may enter the sewer in either original parent compound or metabolite (Helwig et al. 2016). Depending on the properties of pharmaceuticals, only part of them is removed by the ordinary microbiological treatments in wastewater treatment plants (WWTPs), whereas the remaining residue is discharged and dispersed in the aquatic environment (Abellán et al. 2007; Sangion and Gramatica 2016). Due to that, WWTPs are often recognized as the main route of entry for pharmaceuticals in the environment, leading to a ubiquitous and continuous contamination (Quadra et al. 2016; Sangion and Gramatica 2016). Besides, the improper disposal of unused, expired and surplus pharmaceuticals into the drains or toilets is another important pathway to contaminate the environment (Al-Odaini et al. 2013; Moctezuma et al. 2012; Wu et al. 2012). These pharmaceuticals are most probably infiltrated into the groundwater depending on the hydrology system (Quadra et al. 2016).

In addition, veterinary use is also an important source of drugs to the environment. Abundant of veterinary pharmaceuticals is applied in husbandry sector as a growth promoter, for breeding and therapeutic purposes (Bundschuh et al. 2016; LA Ioannou et al. 2011; Kümmerer 2009; Sim et al. 2011). After the consumption of pharmaceutical by the livestock, part of the pharmaceutical is excreted through the urine and feces, in either metabolized or parent form. Without any treatment, the excreted pharmaceuticals get into the soil and groundwater directly (Kümmerer 2001; Quadra et al. 2016). Often, livestock’s manure is used as fertilizer in the agricultural field. The manure which contains the pharmaceutical residues can be either mobilized into surface water during heavy precipitation or infiltrated into the groundwater (Abellán et al. 2007). Other than livestock, fish farming is also an important source of pharmaceuticals (Quadra et al. 2016). The direct application of pharmaceuticals in the aquaculture for the prevention and treatment of microbial infections has caused the increment of retained pharmaceuticals in the aquatic environment (Kümmerer 2009).

Also, pharmaceuticals are extensively applied in the agricultural and farming fields to control the bacterial disease (Fukahori et al. 2012; Kümmerer 2009; Mozia and Morawski 2012). These pharmaceuticals can accumulate in farmland and eventually reach the natural water sources through leaching and runoff (Abellán et al. 2009; Wilkinson et al. 2016). Last but not least, production and manufacturing are among the industries which have highly contribute to the occurrence of pharmaceutical pollution through the inappropriate disposal, accidental spillage during the manufacturing and distribution processes (Al-Odaini et al. 2013; Yang et al. 2008a), as well as the direct discharge of pharmaceutical waste into the water sources (Abellán et al. 2007; Emmanuel et al. 2005; Gautam et al. 2007; LA Ioannou et al. 2011; Kümmerer 2001).

Once the pharmaceutical residue in the environment, their behavior can be significantly affected by some factors such as solubility, chemical structure, persistence, sorption behavior, climatic factors (temperature, precipitation), water body properties (pH, redox potential, organic carbon content), composition of sediments and environmental degradation. Due to this immense complexity, more research in this field is required to identify the behaviors of drugs in the environment (Quadra et al. 2016). Furthermore, strategies are required for the removal of numerous dominant pollution sources. Besides the enactment of appropriate legal measures, a standard or guideline of pharmaceuticals wastewater effluent is also required to be invented.

Pharmaceuticals mitigation strategies

Pharmaceuticals are often poorly removed by conventional wastewater treatment techniques (K’oreje et al. 2016). The continual emission of pharmaceuticals (either in parent form or metabolites) into the surface water sources not only causes the ubiquitous contamination of freshwater supplied, but it is also proved to induce some adverse effects to the aquatic organisms particularly in terms of endocrine disruptions (Khataee et al. 2013; Talib and Randhir 2016). Reported strategies in this regard are thus reviewed as tabulated in Table 3 to evaluate and compare the different solutions which have been suggested.

Table 3 Review of studies examining the strategies for the mitigation of pharmaceuticals in the aquatic environment

Besides depending on the wastewater treatment process such as the most promising advanced oxidation processes (AOPs) for the mitigation of pharmaceuticals in the aquatic environment, there are some other solutions which have been suggested and discussed as presented in Table 3. Among the suggested pharmaceuticals abatement strategies, take-back program is the only strategy which currently exists and being the most recognized upstream strategies (Blair 2016). This program provides plenty of benefits by retrieving the unused pharmaceuticals, but at the same time, its limitations are capable of restricting it from the worldwide application. Next, source treatment such as urine separating toilets can be an effective way of discarding the retained pharmaceuticals in the urine, but the pharmaceutical residues in the feces have been sadly neglected. In this case, this treatment will be unable to provide a thorough elimination of pharmaceuticals and can most probably increase the complexity of the treatment process and cost.

On the other hand, it can be observed that the trash disposal is the simplest and cost-saving technique to be implemented. Yet, it may not be the most secure solution since it can induce the same environmental problem through leaching from landfill and accidental exposure if there is incautious handling. As for the invention of green pharmaceuticals, although it may be costly in terms of pharmaceuticals research and development, but its ease to degrade and less harmful properties contribute to the sustainable protection of aquatic resources. There are some newly discovered strategies like starting new prescriptions at lower dosages (Daughton 2003). In this regard, patient is advised to start with the lowest effective dose and adjusting the dosage as necessary. This prescript way not only reduces the patient costs and unused pharmaceuticals disposal cost, but it also improves the therapeutic efficacy and prevents the unnecessary side effects to the patient, as well as avoids the accidental exposures and emission of pharmaceuticals to the aquatic environment. Last but not least, the mitigation technique which is known as “eco-directed sustainable prescribing” is mainly about the selection of pharmaceuticals with lower excretion rate (Daughton 2014). Unlike the former strategy (lower prescription dose), this solution emphasizes on the metabolism and excretion of pharmaceutical drugs rather than the initially ingested dose by the patient, because the emission of pharmaceuticals into the environment via sewers is dictated by the excretion profile and pharmacokinetics of the different types of pharmaceutical compounds. This solution involves the reduction in dose of medications with high excretion profile and replaces with another suitable medication which is poorly excreted, if possible. Nevertheless, the understanding on the effectiveness, usage, participation and feasibility of this strategy is still incomplete.

In summary, an ideal solution for the pharmaceuticals mitigation in the aquatic environment is yet to be met. The above-discussed strategies which equip with both limitation and strength may require further investigation to compensate the scarcity of the information and subsequently identifying the most effective strategy for real application.

Heterogeneous photocatalyst

During the last decade, AOPs appears to be a promising wastewater treatment technology which could successfully degrade the soluble organic pollutants and the volatile organic compounds retained in the water and air, respectively. The only chemical property which unites the different types of AOPs is the generation of reactive oxygen species (ROSs), particularly the hydroxyl radical (·OH), which is a powerful oxidizing agent that possesses the second highest oxidizing potential (2.8 eV). It can be generated in situ to oxidize and further mineralize the recalcitrant pollutants into the harmless end products such as carbon dioxide and water (De la Cruz et al. 2013; Kaur et al. 2016; Xekoukoulotakis et al. 2011; Yahiat et al. 2011).

AOPs such as Fenton, photo-Fenton, ozonation, ultrasound radiation, photolysis and photocatalysis are applied for the treatment of pharmaceutical wastewater. However, these treatment processes are found to be less effective with the fluctuating degree of removal efficiency. The tertiary treatment methods such as electrodialysis, activated carbon, chemical removal, coagulation, filtration and membrane filtration are also examined for their removal efficiency of pharmaceutical compounds retained in the wastewater after secondary treatment. Yet, the efficiencies of these methods are observed to be fluctuated critically (Kaur et al. 2016).

To date, heterogeneous photocatalysis has been known as the most distinctive, popular, effective, interesting and promising wastewater treatment technique for the removal of recalcitrant and persistent contaminants (Aguilar et al. 2011; Maroga Mboula et al. 2012; Yahiat et al. 2011; Yang et al. 2008a). This treatment process is initiated by the interaction between the UV and catalyst, where it can be simplified as “the speeding up of photoreaction in the presence of a catalyst” (Al-Rasheed 2005; De la Cruz et al. 2013). It utilizes the near ultraviolet band of the solar spectrum (<400 nm) to excite the catalyst integrated with the presence of oxygen and water (LA Ioannou et al. 2011). Then, the generated ROSs are applied for the destruction of contaminants appeared in the water body. Among the photosemiconductors, titanium dioxide (TiO₂) with anatase phase appears to be the most extensively used photocatalyst due to its idealizing properties such as high stability, cost-effective and favorable performance (Kaur et al. 2016).

Mechanisms of heterogeneous photocatalysis

Numerous studies have been published on the reaction mechanism of photocatalytic process using TiO₂ (Al-Rasheed 2005; Elmolla and Chaudhuri 2010b; Ibhadon and Fitzpatrick 2013; Jaeger and Bard 1979; Moctezuma et al. 2012; Yang et al. 2008a, b). Heterogeneous photocatalysis can be defined as the acceleration of photoreaction in the presence of semiconductor photocatalyst. Among the variety of catalyst, TiO₂ is mostly preferred in the photocatalysis process for features such as chemical stability, acceptable band gap, ability to adsorb electrons and low cost (Gani and Kazmi 2016). Figure 2 illustrates the simplified mechanisms for the photoactivation of a semiconductor photocatalyst, TiO₂. As shown in Fig. 2, the valence and conduction bands of a TiO₂ are separated by a band gap or energy gap. In order to initiate the degradation process, TiO₂ requires photoexcitation with light at a wavelength of <387 nm, to exceed the band gap of the active anatase phase of 3.2 eV and rutile phase of 3.0 eV (Ibhadon and Fitzpatrick 2013). In other words, photocatalysis over a TiO₂ is initiated by the absorption of photons with energy equal to or greater than its band gap. This promotes the movement of electron from the valence band to the conduction band of TiO₂. Subsequently, it generates the positive valence band hole $\left( {{\text{h}}_{\text{vb}}^{ + } } \right)$ and negative conduction band electron $\left( {{\text{e}}_{\text{cb}}^{ - } } \right)$:

Fig. 2

Simplified mechanisms for the photoactivation of a semiconductor catalyst (Al-Rasheed 2005)

$${\text{TiO}}_{ 2} + {\text{hv}} \to {\text{e}}_{\text{cb}}^{ - } \left( {{\text{TiO}}_{ 2} } \right) + {\text{h}}_{\text{vb}}^{ + } \left( {{\text{TiO}}_{ 2} } \right)$$

(1)

The electron and hole can recombine when there is a lack of oxygen to react with the electron for the formation of ${\text{O}}_{2}^{ - \cdot }$. During the recombination, the absorbed light energy released as heat with no chemical reaction takes place (Ibhadon and Fitzpatrick 2013).

As a result of irradiation, TiO₂ can act as an electron donor or molecules acceptor. The powerful oxidant, ${\text{h}}_{\text{vb}}^{ + }$, oxidizes the water and hydroxide ion (${\text{OH}}^{ - }$) to produce the ^·OH, whereby the reductant, ${\text{e}}_{\text{cb}}^{ - }$, reduces the oxygen to form superoxide radical anion (${\text{O}}_{2}^{ - \cdot }$). ${\text{O}}_{2}^{ - \cdot }$ then reacts with hydrogen ion (${\text{H}}^{ + }$) to form hydrogen peroxide radical (${\text{HO}}_{2}^{ \cdot }$) and further protonated by ${\text{H}}^{ + }$ can produce hydrogen peroxide (H₂O₂). These oxidation and reduction processes which take place on the surface of the photoexcited semiconductor not only generate abundant of ROSs such as ^·OH, ${\text{O}}_{2}^{ - \cdot }$, ${\text{HO}}_{2}^{ \cdot }$ and H₂O₂ which takes part in the contaminant degradation process, but also prevent the recombination of ${\text{h}}_{\text{vb}}^{ + }$ and ${\text{e}}_{\text{cb}}^{ - }$. The following chain reactions have been widely postulated (Al-Rasheed 2005):

$${\text{TiO}}_{2} ({\text{h}}_{\text{vb}}^{ + } ) + {\text{H}}_{ 2} {\text{O }} \to {\text{TiO}}_{ 2} + {\dot{\text{O}}\text{H}} + {\text{H}}^{ + }$$

(2)

$${\text{TiO}}_{ 2} ({\text{h}}_{\text{vb}}^{ + } ) + {\text{OH}}^{ - } \to {\text{TiO}}_{ 2} + {\dot{\text{O}}\text{H}}$$

(3)

$${\text{TiO}}_{ 2} ({\text{e}}_{\text{cb}}^{ - } ) + {\text{O}}_{2} \to {\text{TiO}}_{ 2} + {\text{O}}_{2}^{ - \cdot }$$

(4)

$${\text{O}}_{2}^{ - \cdot } + {\text{H}}^{ + } \to {\text{HO}}_{2}^{ \cdot }$$

(5)

$${\text{HO}}_{2}^{ \cdot } + {\text{H}}^{ + } + {\text{TiO}}_{ 2} ({\text{e}}_{\text{cb}}^{ - } ) \to {\text{H}}_{2 } {\text{O}}_{2}$$

(6)

$${\text{O}}_{2}^{ - \cdot } + {\text{O}}_{2}^{ - \cdot } + 2{\text{H}}^{ + } \to {\text{H}}_{2 } {\text{O}}_{2} + {\text{O}}_{2}$$

(7)

On the other hand, the cleavage of H₂O₂ by one of the reactions below can also generate ·OH:

$${\text{H}}_{2 } {\text{O}}_{2} + {\text{hv }} \to 2 {\dot{\text{O}}\text{H}}$$

(8)

$${\text{H}}_{2 } {\text{O}}_{2} + {\text{O}}_{2}^{ - \cdot } \to {\dot{\text{O}}\text{H}} + {\text{O}}_{2} + {\text{OH}}^{ - }$$

(9)

$${\text{H}}_{2 } {\text{O}}_{2} + {\text{TiO}}_{2} ({\text{e}}_{\text{cb}}^{ - } ) \to {\dot{\text{O}}\text{H}} + {\text{OH}}^{ - } + {\text{TiO}}_{ 2}$$

(10)

The ROSs (^·OH,${\text{O}}_{2}^{ - \cdot }$, ${\text{HO}}_{2}^{ \cdot }$ and H₂O₂) including ${\text{h}}_{\text{vb}}^{ + }$ and ${\text{e}}_{\text{cb}}^{ - }$ then degrade the organic compounds adsorbed on the surface of photocatalyst and suspended in the solution. Although the degradation commences with a partial degradation, the term photocatalytic degradation usually refers to the complete photo mineralization or oxidation, essentially to the harmless end products of water and carbon dioxide (Saadati et al. 2016). ^·OH is verified to be the most abundant and dominant oxidizing species since it degrades the organic compounds directly in a TiO₂ aqueous suspension (Moctezuma et al. 2012; Yang et al. 2008a).

Titanium dioxide (TiO₂) as photocatalyst

Among the photosemiconductors (ZnO, ZrO₂, MgO, MoO₃, CdS, SnO₂, WO₃, etc.), TiO₂ is the most extensively used photocatalyst due to its biological and chemical inertness, non-toxicity, low cost, high catalytic efficiency and photochemical stability (Abellán et al. 2009; Aguilar et al. 2011; Ji et al. 2013; Laoufi et al. 2013). Besides, with the ideal properties such as excellent pigmentary properties, high UV absorption and resistance to photocorrosion in aqueous environment, eco-friendly, low energy band gap and can be applied individually without additional chemicals, TiO₂ remains a benchmark among other semiconductors (Abellán et al. 2007; Al-Rasheed 2005; Belgiorno et al. 2007; Choina et al. 2013; Lofrano et al. 2009; Yang et al. 2008a).

Basically, TiO₂ has three different crystalline forms. Anatase and rutile are the most common forms. Anatase is more efficient than rutile in the photocatalysis application since the former crystalline form has an open structure and exhibits higher photocatalytic activity, whereby brookite is the third crystalline form which is uncommon and unstable to be used in the photocatalysis treatment process. The commercial TiO₂ powder, such as anatase crystalline, and the combinations of anatase and rutile (Degussa P25, 25:75 or 80:20 anatase/rutile) have been the most extensively used heterogeneous catalysts in the photocatalysis treatment process due to their chemical stability, reproducibility, highest detoxification efficiencies and readily available as a catalyst for oxidation processes (Al-Rasheed 2005; Spasiano et al. 2015).

Suspended TiO₂ powder and immobilized TiO₂ are the two different modes of TiO₂ photocatalyst which are typically used in the photocatalytic degradation processes. Both of them offer their respective advantages and disadvantages as tabulated in Table 4. The slurry or suspended TiO₂ has been the most commonly used system because of its simplicity in terms of preparation and application. The suspended TiO₂ system can provide a higher efficiency than the immobilized system, mainly due to a higher ratio of catalyst active site to reaction volume. Nevertheless, an additional separation process is required to recover the TiO₂ powder at the end of the treatment process, by either filtration or centrifugation. This separation process not only increases the complexity and cost of the overall process, but it is also time-consuming (Spasiano et al. 2015). Furthermore, the suspended TiO₂ powder tends to agglomerate into larger particles at high concentration, which could reduce the catalytic activity (Hao et al. 2012; Lalhriatpuia et al. 2015). On the other hand, the immobilized TiO₂ system allows the direct discharges of decontaminated water effluent without the recovery of TiO₂ since the catalyst remains confined to the packed-bed (Borges et al. 2015). Consequently, the post-processing treatment can be avoided, thereby saving time and costs (Hashim et al. 2017). However, as compared to the suspended catalyst, it is reported that 60–70% of reduction in performance has been observed in the aqueous system for immobilized TiO₂ since the latter system offers a lower reaction surface area for the photocatalysis reaction to take place (Bautista et al. 2015; Gaya and Abdullah 2008; Jiménez et al. 2015). Besides, the immobilized catalyst is more difficult to be synthesized and it requires the inert support materials such as glass or ceramic fibers, alumina pellets or molecular sieves (Spasiano et al. 2015). Despite aforementioned disadvantages, currently, coated photocatalyst and immobilization techniques are still investigated intensively due to the assumption that this system is more effective in the removal of organic compound as compared to the suspended TiO₂ (Gaya and Abdullah 2008).

Table 4 Advantages and disadvantages of the suspended and immobilized TiO₂

Besides being a promising photocatalyst in the wastewater treatment process, TiO₂ is also an important material in many commercial products, ranging from drugs to foods, paints to pharmaceuticals, cosmetics to catalysts and sunscreens to solar cells, where TiO₂ is applied as a desiccant, brightener and reactive mediator. TiO₂ is used as the inactive ingredients in the food products up to 1%, as permitted by the U.S. Food and Drug Administration. The health effects associated with the consumption and application of TiO₂ are still not clearly known (Ibhadon and Fitzpatrick 2013). So far, only Gaya and Abdullah (2008) has mentioned on the toxic effect of the TiO₂ suspension on the E. coli. Also, the increased antibacterial inhibition is observed with the increment of TiO₂ loading during the photocatalytic experiment. Therefore, more studies are required to further investigate the effect of TiO₂ on the environment and organisms. Meanwhile, the regulatory framework for the use of TiO₂ in the food products should be established in the near future, particularly in the developing nations (Ibhadon and Fitzpatrick 2013).

Advantages and limitations of heterogeneous photocatalysis

Apparently, current conventional water and wastewater treatment processes have failed to overcome the pharmaceutical pollution as they are not designed to remove the suspended pharmaceuticals (Blair 2016). To date, heterogeneous photocatalytic degradation using TiO₂ photocatalyst remains as a viable alternative in the elimination of organic contaminants persistent in both aquatic and atmospheric (Gaya and Abdullah 2008). Since the last decade, this wastewater treatment technique has been extensively applied for the elimination of different types of pharmaceuticals. Table 5 summarizes previous studies on the heterogeneous photocatalysis treatment technique for the degradation of pharmaceuticals. It is noticeable in Table 5 that the initial concentration of pharmaceutical employed in the previous studies was usually higher than that typically detected in the natural water sources (µg/L–ng/L). This is to allow the accurate determination of residual concentration and the assessment of treatment efficiency within a measurable time scale (Achilleos et al. 2010). As shown in Table 5, most of the TiO₂ photocatalytic studies focused on the determination of optimal operating conditions to attain the best performance in terms of degradation and mineralization. Markedly, the degradation rate of pharmaceutical is greatly affected by the operational parameters such as the type and loading of photocatalyst, initial concentration of the pharmaceutical under investigation, pH of the solution and light (source, wavelength and intensity). Other operational parameters which can enhance the degradation rate include the addition of co-oxidants and the concentration of electron acceptors. Moreover, the design and geometry of the photoreactor also influence the optimal degradation rate of pharmaceutical (Kanakaraju et al. 2014). Due to this, different optimum operating conditions are normally documented by the different studies for the highest pharmaceutical removal efficiency (regardless of the studied pharmaceuticals are different or similar), since the degradation rate of pharmaceutical is dictated by a great deal of aspects and parameters. Here, there are three main advantages associated with this treatment method and could be explained from the aspects of health and safety, sustainability as well as the simplicity of technology.

Table 5 Recent examples of pharmaceuticals photocatalytically degraded by TiO₂

Various types of advanced treatment methods such as activated carbon adsorption, air stripping and reverse osmosis have been applied for the elimination of retained pharmaceuticals. Yet, studies have found out that these processes are less effective for the overall mineralization, which only transfer the pharmaceutical compounds from one phase to another or just collecting the pharmaceutical compounds without eliminating them (Elmolla and Chaudhuri 2010b; Gültekin and Ince 2007). Besides, the purification techniques like ozonization, chlorination and filtration too have their own limitations in terms of the energy sources consumption and the generation of harmful waste (Sharma et al. 2012). However, in contrast with the aforementioned treatment methods, heterogeneous photocatalyst which relies on the generation of ROSs is able to render the complete mineralization of pharmaceuticals (Kaan et al. 2012). Among the variety of ROSs, ^·OH has attracted the most attention. The positive characteristics of ^·OH radicals are including non-selective nature, high oxidation potential (2.8 eV) when compared to other oxidants, ability to react with a wide range of contaminants without any additives, as well as rate constants normally in the order of 10⁶–10⁹ mol/L/s (Kanakaraju et al. 2014). During the photocatalysis treatment process, ^·OH appears to be a strong oxidant that can react and further break down the non-biodegradable or recalcitrant compounds (such as pharmaceuticals) in water or wastewater, from complex molecules into the simplest and non-hazardous end products such as water and carbon dioxide (Elmolla and Chaudhuri 2010b; Khataee et al. 2013; Lofrano et al. 2009). Therefore, heterogeneous photocatalysis degradation process can provide promising clean water sources that ensure the health and safety of human, living organisms and the environment.

The growth and development of the world have induced several environmental issues, mainly regarding the depletion of natural resources (Spasiano et al. 2015). It has been circulated worldwide that the depletion rate of these resources is increasing year by year, causing it to become one of the major concern among humans globally. Due to this issue, priority is given to the sustainability concept regardless of sectors. Heterogeneous photocatalyst is one of the wastewater treatment methods which in line with the concept of sustainability. The recent studies start to utilize the natural UV radiation (from sunlight) instead of the synthetic UV radiation (from UV lamp and solar simulator) as the source of photocatalyst excitation. Meanwhile, the ideal photocatalyst, TiO₂, is found to be water insoluble under most of the environmental conditions and remains unchanged throughout the treatment process (Belgiorno et al. 2007; Choina et al. 2013; Ibhadon and Fitzpatrick 2013). As the main elements of UV radiation and oxygen are unlimited supplied by the solar and atmosphere, respectively, as well as the photocatalyst can be recovered and reused after the treatment process, the photocatalytic technology is considered to be low cost, environmentally friendly, low energy consumption with no consumable chemicals required (Aziz et al. 2016; LA Ioannou et al. 2011).

Heterogeneous photocatalyst treatment which involves a simple operating system with limited equipment required could potentially be used as a standalone treatment. This treatment method is able to attain the complete mineralization with no sludge generated. Therefore, the post-treatment and disposal of sludge can be avoided (Al-Rasheed 2005; Chong et al. 2015; Ibhadon and Fitzpatrick 2013). Additionally, the achieved photocatalysis removal efficiencies of pharmaceuticals in the previous studies are believed to be sufficient for the actual treatment process. In other words, the photocatalytic degradation of pharmaceuticals in the real situation is likely to occur rapidly since the concentrations of pharmaceuticals detected in the natural water sources (µg/L–ng/L) are far lower than that employed in the previous studies. Hence, this treatment method is able to perform effectively for a technical use in the wastewater treatment plant. Besides, it is a totally safe treatment method which is conducted under the ambient temperature and ordinary pressure (Aziz et al. 2016).

Despite the aforementioned advantages, there are also some limitations associated with the application of photocatalysis. The main limitation is that this method is unable to perform well in turbid water. This is because the reduction of light transmissivity, the adsorption of contaminants onto the surface of catalyst or the absorption of available photons by the contaminants will eventually induce a lower intensity of photons to excite the catalyst surface (Abellán et al. 2009; LA Ioannou et al. 2011; Kümmerer 2009; Yang et al. 2008a). Therefore, heterogeneous photocatalysis treatment is unable to integrate with primary and secondary treatment process, but it is suggested to be used as a tertiary treatment process, particularly for the elimination of pharmaceutical compounds which are still retained in the treated wastewater (Naddeo et al. 2009).

Another major limitation is that TiO₂ can only be photoexcited by the light at a wavelength of <388 nm due to its wide band gap (3–3.2 eV) (Achilleos et al. 2010; Daghrir and Drogui 2013). Therefore, it is important to avoid any loss of solar radiation during the treatment process. For better results, this treatment process can be assisted by the artificial illumination of catalyst to achieve the degradation of contaminants in time that is practical for the real wastewater treatment processing (Ibhadon and Fitzpatrick 2013). Besides, it is suggested that the nanomaterial should be modified so that it can utilize the visible light in solar irradiation (Kaur et al. 2016).

Last but not least, heterogeneous photocatalysis process must be operated cautiously to avoid the incomplete mineralized organic contaminants to be released into the water sources. It is important to highlight that the ultimate goal of the treatment process should be emphasized on the complete mineralization of pollutants, since the previous studies have reported that the metabolites and intermediates generated during the treatment process can be more toxic than the parent compounds (Kümmerer 2009; Maroga Mboula et al. 2012; Nasuhoglu et al. 2011). For instance, Szabo and his co-researchers have reported that the intermediates of paracetamol (e.g., acetamide, hydroquinone) have posed a higher toxicity level as compared to paracetamol itself (Szabó et al. 2012). Besides, the phenolic intermediates of paracetamol which are classified as the persistent organic pollutants are found to be toxic for both environment and human beings (Torun et al. 2015).

Future trends

Maroga Mboula et al. (2012) indicated that the complete mineralization of contaminants under the heterogeneous photocatalyst treatment method is associated with a high operating cost caused by the excessive consumption of energy and TiO₂. In order to minimize the overall cost of photocatalysis treatment process and to overcome the depletion of non-renewable energy resources, scientists are currently searching for a new energy resource that is clean, renewable and alternative to the fossil fuels. Among the alternative sources, solar, which is derived from the sunlight, was recognized as the most promising natural energy source. This potential energy can be converted into chemical energy by natural solar photoassisted reactions (Spasiano et al. 2015). Table 6 shows the recent studies applying the solar radiation for the photocatalysis degradation of pharmaceuticals. It can be observed that the solar heterogeneous photocatalysis has been an efficient technique for the elimination of pollutants from aqueous. As photocatalysis makes use of sunlight for UV radiation, the technology is inexpensive, environmentally friendly and can be applied worldwide. Also, it requires only minimal equipment, which is highly deployable and appropriate for developing countries and remote sites with no access to electricity (Ibhadon and Fitzpatrick 2013).

Table 6 Recent studies applied the solar radiation for the photocatalysis degradation of pharmaceuticals

TiO₂ remains as a benchmark and excellent photocatalyst among other semiconductors due to its ideal properties (Kaan et al. 2012). The main drawback which currently restricts its wider commercial application is the limited solar spectrum to be used (limited to ultraviolet region), which is only about 3–4% of the solar energy reaching the terrestrial surface. Therefore, much effort has been devoted to the development of visible-light-harvesting photocatalysts through the reduction in catalyst’s band gap to increase the amount of visible sunlight which TiO₂ can absorb (Spasiano et al. 2015). Other inventions include the increment of catalyst surface area, active site and photon energy absorption (Al-Rasheed 2005; Ibhadon and Fitzpatrick 2013). Additionally, the retrieval and reuse of TiO₂ is also an essential issue to be resolved. There are a few TiO₂ retrieval methods which have been suggested for the recovery of TiO₂ suspended in the reaction mixture in aqueous slurry systems. Ultracentrifugation and membrane filtration separation methods are efficient in the separation of nanomaterials, but both of them have their own limitation of high energy consumption and easily to be blocked, respectively. Compared to the aforementioned methods, the magnetic separation method is considered a rapid and effective technique for the recovery of nanoparticles (Bagheri et al. 2016). Nevertheless, Saadati et al. (2016) have mentioned that future studies should focus on the immobilized system, where the photocatalyst is immobilized on suitable support matrices to avoid the post-separation and recovery of the catalyst particles at the end of the treatment process. Overall, each of the recovery methods equipped with advantages and disadvantages. The selection of method should be based on the quality standards which have to be met, efficiency and cost (Bagheri et al. 2016).

Besides the replacement of artificially generated photons with the natural solar irradiation and the modification of TiO₂, there are some barriers and lacking parts which still need to be overcome in the near future:

• Although solar photocatalysis has produced significant interest in research on nowadays, so far, there is a lack of “in situ” experiments on the long-term reliability of solar operation (Spasiano et al. 2015).

• Photoreactor is a specific device which is used to convey the solar photons and chemical reagents to in contact with the photocatalyst efficiently. Unlike the classic chemical reactors, solar photoreactors more concern on the physical geometry to ensure the effective collection of solar radiation for the optimal photocatalytic treatment process, as well as the uniform distribution of sunlight inside the photoreactor, as the poor distribution may reduce the overall efficiencies of the photochemical process. However, studies have found out that the design and scale-up of a solar photoreactor is one of the major problems associated with the application heterogeneous photocatalyst treatment method, where it is very difficult to reproduce the same ratio of irradiated surface to total volume during scale-up (Aziz et al. 2016; Spasiano et al. 2015).

• Future research should prioritize on the investigation of AOPs under real treatment conditions since the literature about real field applications of AOPs is very scarce, which may limit the wider application of so far obtained data (Gani and Kazmi 2016).

• More investigation should be conducted to acquire more data on the environmental occurrence of human and veterinary pharmaceuticals in use today, so that a proper estimation of exposure to pharmaceuticals in environmental and drinking water, and their potential risks to the ecosystem and human health can be assessed (K’oreje et al. 2016).

• So far, there is a notable lack of evidence regarding the harmfulness of the retained pharmaceuticals, particularly on the human health. Although information on the potential environmental risks of pharmaceuticals is available, this effect cannot be easily extrapolated to the human harm. Therefore, extra findings on the potential biota and human health effects are required, in both low-level and long-term exposure. Besides, information regarding the impact of pharmaceuticals in drinking water (often in the ng/L range) is also incomplete (Blair 2016; Quadra et al. 2016).

• Abundant of studies deals with the removal of pharmaceutical individually instead of pharmaceuticals mixture which simulates the real wastewater matrix (Rizzo et al. 2009). In this regard, the extra concern should be given to the synergistic effects of the multiple compounds on both ecological and human health (Ji et al. 2013). In addition, Nasuhoglu et al. (2011) have indicated that the intermediates generated during the pharmaceuticals treatment process are found to be more toxic and higher retained concentrations as compared to the parent compounds. Therefore, the pharmaceutical metabolites should also be given the similar attention to identify their hidden toxic potential on both ecological and human health. Besides the endocrine disruption, further research should focus on the possible disruption to other biological systems (such as nervous and immune systems), especially in system development during pre-/perinatal exposure periods (Wilkinson et al. 2016).

Conclusion

Water pollution by persistent pharmaceutical compounds is an ever-increasing environmental problem concerned globally. In this regard, more research is crucially required to obtain more information about the effects of pharmaceuticals in both parent and metabolites forms, in single and mixture conditions, as well as in low-level and long-term exposure. These findings are particularly important to human being as it can become a convincing fact to alert the society regarding the seriousness of the pharmaceutical pollution. On the other hand, while the solar photocatalysis treatment process has emerged as a reliable, sustainable, environmentally friendly and economical treatment technology, its application is constrained by several major technical issues mainly related to the main elements in the photocatalysis process such as photocatalyst, solar UV source and photoreactor. Further investigation, modifications and improvements on these important elements can be implemented to increase the industrial acceptance as well as the effectiveness and practical application of this treatment technique in the real wastewater treatment system.