Treatability of Pharmaceutical Wastewater by Using Combined Ultrasound Cavitation and Persulfate Process

10 In recent years industrialization caused, magnificent leaps to high profitable growth of 11 pharmaceutical industries, however, simultaneously it has given rise to environmental pollution. 12 Pharmaceutical processes like extraction, purification, formulation etc. generates huge volume of 13 wastewater with high COD, biological oxygen demand, auxiliary chemicals, and different 14 pharmaceuticals substance or their metabolites in the active or inactive form imparting intensive 15 color, which necessitates its proper treatment before being discharged. This study focuses on the 16 feasibility analysis of utilization of ultrasound cavitation assisted with persulfate oxidation 17 approach for the treatment of such complex effluent. Process parameters like pH, amplitude 18 intensity, oxidant dosage was optimized for COD removal applying response surface 19 methodology-based Box Behnken design. The optimum value observed for pH, amplitude 20 intensity, oxidant dosage is 5, 20%, 100 mg/L respectively with 39.5% removal of COD and 21 6.5% removal of TOC in 60 min of fixed processing time. Study confirms that acombination of 22 ultrasound cavitation and persulfate is a viable option for the treatment of pharmaceutical 23 wastewater than individual treatment and it can be used as an intensification technique in 24 existing treatment plants for achieving maximum COD removal.


28
Environmental pollution is one of the global challenge of today's world (Spina et al., 2012;Singh 29 & Prashant, 2017). Amongst that, industrial effluent and other hazardous discharge from 30 industries is one of the prime concerns for developing countries like India. In India one-third 31 portion of water pollution in the natural water bodies and marine pollution are induced by 32 industrial wastewater (Kansal et al., 2013;R. Singh & Prashant, 2017), U.S EPA reported daily 33 effluent produced from pharmaceutical unit as 1.0068× 10 9 L (Adishkumar et al., 2012). Because 34 of these effluents, containing highly biological active compound which is likely cause health 35 harm to human and animals, and also promote the development and spreading of antibiotic 36 resistance genes although the concentration of pharmaceutical residue present in effluent is less. 37 This antibiotic resistance gene interrupt the ecological balance of aquatic environment by 38 initiating irreversible transformation to aquatic fauna (Ng et al., 2014;Tiwari et al., 2020). 39 Industrial wastewater quality is estimated based on the amount of organic matter present as COD 40 (chemical oxygen demand), total carbon, biological oxygen demand, and other wastewater 41 quality parameter and nowadays the high amount of pharmaceutical substances used for the 42 protection and cure of diseases for humans and animals therefore, huge amount of wastewater 43 generated in pharmaceutical industries (Mohapatra et al., 2014;Ghafoori et al., 2015). Over 60% 44 of pharmaceutical sectors meet country's demand and is one of rapid expanding sectors of Indian 45 economy. The produced wastewater from pharmaceutical sectors are complex and hazardous in 46 nature, high COD, biological oxygen demand, solid Containing supplementary chemicals and 47 presence of pharmaceuticals secondary metabolites leads the wastewater to be a under "red 48 category" (Gadipelly et al., 2014;Martínez et al., 2018;Changotra et al., 2017Changotra et al., , 2019. 49 Pharmaceutical wastewater contains the majority of pollutants recalcitrant or bio-refractory 50 substances which are very difficult to degrade (Grandclément et al., 2019). Thus it is necessary 51 to treat pharmaceutical wastewater efficiently sooner than discharging it into any water bodies to 52 avoid hazards to the environment and ecosystem (Gadipelly et al., 2014;Martínez et al., 2018;53 Changotra et al., 201753 Changotra et al., , 2019. 54 Conventional treatments cannot efficiently treat recalcitrant or bio-refractory molecules present 55 in industrial effluent and sometimes it also get converted in another complex by-product as 56 Fluoxetine and endocrine disruptors which has resulted multitude of undesirable problems like 57 harm the reproduction, metabolism of aquatic organism and feminization of fish population 58 (Ford & Fong, 2016;Huang et al., 2016) which are not easily biodegradable which further 59 pollutes water bodies (Singh & Prashant, 2017). Treatments like biological oxidation required 60 longer time because it is slower reaction rate (Crini & Lichtfouse, 2019) chemical coagulation is 61 useful for removal of waste material in form of colloidal or suspended that do not settle very 62 quickly it requires longer time & more sludge production (Verma et al., 2012) chemical 63 oxidations target selective bio resistant compound it can be used as pretreatment (Mantzavinos & 64 Psillakis, 2004) and adsorption reactors rapidly get clogged and its regeneration is costly and it 65 decreases acceptance of certain type of metal ions (Crini & Lichtfouse, 2019), due to this 66 demerits treatments are not efficient to remove all the hazardous compounds effectively from 67 pharmaceutical wastewater ( Jeworski & Heinzle, 2000;Ayare & Gogate, 2019). In recent times 68 advance oxidation process (AOP) such as Fenton oxidation (Singh et al., 2013) ozonation 69 (Cortez et al., 2010) ultraviolet/hydrogen peroxide (Hu et al., 2011) ultrasound cavitation (Gągol 70 et al., 2018) have been considered as a useful process for treatment of bio-refractory pollutants 71 (Q. Yang et al., 2015). Among the AOP, ultrasound cavitation-based process has seen as a 72 promising process for the oxidation of various pollutants in industrial wastewater. Principle 73 behind ultrasonication process is pressure variation in liquid caused by inducing ultrasound 74 which produces cavitation for the treatment of wastewater (Thanekar & Gogate, 2019).

75
Cavitation occurs due to pressure difference in outer flow and inside the system pressure induced 76 by sound waves as system pressure decrease or increase in flow velocity produce small cavities 77 which starts to grow longer compare to higher system pressure (Dular et al., 2016). Furthermore, 78 variation of pressure leads to cavity formation, growth, and its collapse over micro-scale 79 duration. These three-stage occurs during ultrasound cavitation process which leads to generate 80 free radicals and release a large amount of energy up to 5000K temperature and 1000 Atm 81 pressure in wastewater known as "local hotspot" which can be extremely suitable for the 82 oxidation of pollutants (Leighton, 1995;Thanekar & Gogate, 2019). The main advantage behind 83 this treatment is it does not require any chemicals to promote oxidation, no sludge formation, no 84 visible light require (Vega & Peñuela, 2018), break up agglomerates (Jordens et al., 2016;Dong 85 et al., 2020). Ultrasound cavitation is useful for the treatment of active pharmaceutical compound 86 like carbamazepine, diclofenac, ciprofloxacin (Beckett & Hua, 2001;Rayaroth et al., 2016).  (Rayaroth et al., 2016). Among the various oxidant, per-sulfate ion enhance degradation 91 of organic matter in the wastewater though the use of combined ultrasound -persulfate system 92 has been less studied (Monteagudo et al., 2015(Monteagudo et al., , 2018Wang & Zhou, 2016). Alternative of 93 hydrogen peroxide, Persulfate ion has gained more attention in the interest of higher redox 94 potential of sulfate radical (2.5 V -3.1V) and expanded life time than hydroxyl radical for 95 advanced oxidation treatment in recent time. Formation of sulfate radical occurs by breakage of 96 O-O bond of Persulfate ions using different activation method like heat (Tan et al., 2012), 97 transitional metals , UV (Xie et al., 2015). Among them, activation by 98 ultrasound acts as an emerging method and typically used for pharmaceuticals ( Zou et al., 2014;99 Yang et al., 2019).

100
In Combined process multiple operating parameters influences or affects the removal efficiency.

101
For complex system governed by several parameters, generally usage of one parameter 102 optimization at a time could provide mis-interpretation due to lack of interaction effect, thus 103 design of experiment is effective tool for optimization, there are various DOE available for 104 optimization of parameters by reducing the number of experiment and cost (Dopar et al., 2011) 105 like box Behnken method of response surface methodology design (RSM) which is a powerful 106 design tool for modeling complex conditions (Tak et al., 2015) and it estimate the relation 107 between manageable input parameter and response variable (Khorram & Fallah, 2018).  Design-expert software was used to prepare DOE. The removal of organic matter from 135 pharmaceutical wastewater was optimized using Box-Behnke design as RSM. Table 2, 136 represents coded and its real value for lower level (-1), mid-level (0), high level (+1) for removal 137 of organic matter as COD another Table 3    value is significant as the p value is less than 0.0500 which implies the model is significant. The 158 significance of p value fixes the error probability of regression co-efficient as significant. For 159 optimized condition of parameter quadratic and some other interaction term are significant, the 160 parameter pH (A) is slightly significant another parameter Persulfate Dosage (C) is significant, 161 an interaction effect of Amplitude Intensity (B) and Persulfate Dosage (C), is also significant 162 with respect to model terms. According to the analysis of variance (ANOVA) selected 163 parameters P-value is less than 0.0500 (P< 0.0500) than selected parameters are significant for 164 the process efficiency and the P-value of parameters is greater than 0.100 (P>0.100) than 165 selected parameters is not significant for the process efficiency.
. Hence, the plot shows that factor B has a prominent effect on COD removal followed by

181
A and C similar to that reflected in the Table of ANOVA.

182
The individual effect of parameter effect plots shown in Fig.3

213
Due to that removal was low at a higher level of pH 8. Especially, at mid-level pH 5 shows 214 maximum removal efficiency rather than another highly acidic pH 2 due to a higher amount of  production rate, increasing amplitude generates more violent collapse of bubbles (Vega & 226 Peñuela, 2018). In this study effect of power dissipation on COD removal was studied by 227 varying Amplitude Intensity from 20 to 80% (Power dissipation -18W to 78W) with fixed pH of 228 5 and Persulfate Dosage of 250 mg/l. The plot shown in Fig. 3 (b), shows the variation of 229 Amplitude Intensity at different levels and its effect on COD removal. A maximum removal 230 estimate at a lower level of 20% (18W) shows that generation of cavitation yield is higher at the 231 lower amplitude and lower at higher amplitude (Feng et al., 2002). The trend of the plot shows 232 that it is not much sensitive towards process efficiency from the lower level to higher level it 233 shows slight curvature, therefore amplitude intensity variation shows least significant favorable 234 by ANOVA as shows in Table 4. The COD removal at 50% and 80% of Amplitude intensity is 235 31.6% and 29.9% respectively. Higher power intensity at lower frequency decoupling effect 236 occurs between sample solution and transducer, thus bubble cloud formation occurs at the 237 surface of the horn or transducer resulting in a reduction of sound waves in the solution, hence at 238 a lower frequency power cavitation becomes more effective (Sunartio et al., 2007). produce sulfate ions and also extra sulfate radicals react itself, as given in Eqn. (7) and Eqn. (8) 258 (Vu et al., 2004;Wei et al., 2018). The additional persulfate loading under particularly acidic 259 solution reported as scavenger, thus rate of reaction slightly decreases with increase in dosage(   Table 4, its P-value is higher than 0.005 (P > 0.005).     (a)Pro le of Individual Parameter Plot with two reference curves based on ANOVA for Process Parameter pH from 2 to 8, with x parameter amplitude of 50%, and Persulfate Dosage of 250 mg/l on Removal of COD with 95% of con dence interval band. (b)Pro le of Individual Parameter Plot two reference curve based on ANOVA for Process Parameter Amplitude from 20%(18W) to 80%(78W) with x parameter pH of 5, and Persulfate Dosage of 250 mg/l at mid-level on Removal of COD (mg/l) with 95% of con dence interval band. (c)Pro le of Individual Parameter Plot two reference curve based on ANOVA for Process Parameter Persulfate Dosage 100 to 400 (mg/l) with x parameter of pH 5 and amplitude of 50% on Removal of COD with 95% of con dence interval band.

Figure 4
Pro le of percentage COD removal with Individual treatment; ultrasound at pH 5, amplitude 20%; Persulfate of 100 mg/l; Combine Effect of ultrasound with persulfate at pH 5 & Persulfate Dosage of 100 mg/l, Amplitude of 20%within 60 min reaction time. Figure 5 (a) Pro le of Interaction effect plot for process parameter pH 2-8 to Amplitude20%-80% (AB) maintaining Persulfate Dosage (mg/l) at middle level (b)Pro le of Interaction effect plot for Amplitude 20%-80% to Persulfate Dosage 100-400 (mg/l) (BC) maintaining pH at middle level (c)Pro le of Interaction effect plot for pH 2-8 and Persulfate Dosage 100-400 (mg/l) (AC) maintaining Amplitude % at middle level