Unlocking biogas production potential Evaluating the environmental impact and biodegradability of ph

Abstract

Keywords: Anaerobic Reactors; Antibiotics; Biogas; Pharmaceutical Wastewater; Medical Waste; Waste Management; Wastewater Treatment

Introduction

Wastes in general, can be categorized into easily degradable, hardly degradable or non-biodegradable materials. Pharmaceutical waste are unused, spilt, or expired drugs or vaccines that is itself an inhibitor in anaerobic digestion systems or in simple terms, ‘hardly degradable’ [1]. Pharmaceutical residues are harmful to natural water sources and are just 3% of medical waste; hence referred to as micropollutants [2–7]. They are found in water bodies due to common usage and manufacturing procedures caused by increased number of emerging pharmaceutical industries [8, 9]. In that sense, nearly, 10,000 liters of pharmaceutical wastewater is generated in India daily [10]. Their characteristics short-life, high organic load and high chemical oxygen demand (COD) makes them difficult to treat using neither physical, chemical or biological means [11–13]. Medical/clinical waste are of human and veterinary origins and includes body fluids, placenta, blood, sharp objects, culture dishes and pathological waste [7]. Anaerobic digestion, as one typical biological treatment process is favored by proteineous medical and pharmaceutical waste in different anaerobic reactors [14–16]. Presently, the effect of only few out of 3000 various medical and pharmaceutical residues in wastewater or pure form (e.g., penicillin bacterial residue) for biogas production has been analyzed [17, 18]. Biofertilizer, biohydrogen and biogas are three resulting by-products of pharmaceutical effluents and medical waste via AD, with near zero carbon emission [19–21]. The technology involves 3-4 intermediate biological decomposition steps and is carried out in fixed dome, balloon or tubular digester and floating drum bioreactors via wet or dry procedures, influenced by several factors [22–27]. Most importantly, pharmaceutical waste/effluents AD is enhanced using various types of microorganisms (e.g., bacteria, protozoa, helminths, microalgae and fungi) and is efficient when proper mixing technology is involved [28–30]. For instance, Clostridium plays an important role in the degradation of compounds containing cellulose and starch, Bacillus helps in the decomposition of proteins and fats and rhizosphere microbiota only degrade plant waste and organisms [23, 27, 31, 32]. Microalgae and blue‐green algae (cyanobacteria) can be used in many ways. Namely, as food by humans, a potential pharmaceutical contaminant remover, heavy metal remover, in biofertilizer production by fixing nitrogen, bioplastic production and as biogas/ biofuel/biodiesel/biohydrogen production ingredient [33– 35]. Contaminants elimination using microalgae follows 3 mechanisms comprising of bioadsorption, biodegradation and accumulation [36]. Microalgal AD is suitable for biogas production as earlier affirmed by scientist since the 1950s [33]. Notably, the same author selectively degrades 9 antibiotics and 1 antidepressant (10 PhACs) at laboratory scale. In 1980s, potentials of fungi species numbering over 14,000 to digest pharmaceutical compounds in effluents, was proposed [37, 38].

An overview of biogas development from the past up to this present time shows that there has been rapid growth in the technology since 1920 in terms of its utilization for street lighting, cooking fuel and transportation fuel [20, 24]. A plant to digest agricultural, municipal and industrial waste, including medical and pharmaceutical wastes had been developed with set target for future multiplication in Skåne, Poland, Pakistan, Austria, Denmark, Turkey, Argentina, Sweden and other European nations [24, 27, 39–45]. Thus, precise aim of building these plants is to reduce organic waste pollution, deforestation, emission reduction and sustainable energy development. But Gittelson et al. [46] lists several reasons why biogas is not sustainable, arguing that the gas is highly toxic, flammable, potentially explosive and contains greenhouse gases which are released via combustion processes and diffusive emissions comparable to manures. The authors also maintained that, transporting biogas would require pipelines with exact problems faced with natural gas (such as leaks and emissions) which did not ‘as believed’ solve the emission issue it was designed to address. However, the new assertion hasn’t been analyzed by scientist to challenge the continuous development of biogas plants across the globe. Moreover, apart from this technology, some wastes, especially of medical and pharmaceutical facilities would lie unattended to, thereby posing serious health issues to humans and animals. Hence, the general objective of this work is to review the pharmaceutical industry and related products and the treatment of wastewaters emerging from them. This work tries to study the dangers associated with medical and pharmaceutical waste in the ecosystem; their possible decomposability, by x-raying their previous exploitation for biogas generation; and the need for future research on these two wastes sources, as specific objectives. This was carried out by studying the pharmaceutical industry products and effluents and their pollution effects and the roles of different bioreactors in enhancing their conversion into useful products.

Literature Review

Pharmaceutical Industry End-users of products from pharmaceutical companies including raw materials, veterinary medicine, antibiotics and cosmetics are humans and animals [47–49]. In pharmaceutical industries, large varieties of these products emanates from five manufacturing processes, namely, fermentation, extraction, chemical synthesis, formulation and packaging [50–52]. Any of these processes has the potential of generating wastewaters containing higher organic loads of harmful constituents to plant, human, animal and aquatic life [48, 50]. The chemical synthesis and fermentation categories of bulk pharmaceutical production process, produces higher volume of wastewater containing salts, recalcitrant organics, spent solvents and pharmaceutical residue (PR) [50, 52]. Currently, the world is witnessing

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

an increased growth in the pharmaceutical industry as core components of the chemical industry [53]. The pharmaceutical supply chain normally has four components, namely, the primary manufacturer, secondary manufacturer, distribution centers, and retail outlets (including hospitals and pharmacies) [54]. Majority of the globe’s largest producers of pharmaceuticals are actively based in Ireland, where considerable amounts are also exported [55]. There are 250 multinational pharmaceutical companies all over India which is regarded as one of the largest and fastest growing industries [56–58]. Andersson & Karlsson [59] reported that, Sweden uses more than 1000 different active substances in about 7600 pharmaceuticals. First pharmaceutical industry in Nigeria was the May & Baker Nigeria Plc founded in 1944 – adding up to over 115 registered manufacturers in Nigeria which started in early 1960s [60]. However, due to high population figures in China, they are understandably, the highest manufacturer and consumers of pharmaceuticals globally [61]. Presently, the largest pharmaceutical company in South Africa, ‘Aspen Pharmacare’, was established in 1850; while ‘Adcock Ingram’, the second largest pharmaceutical firm in the country, trace its roots to 1890 [62]. Pharmaceutical products from Kenya often end up in Uganda, Burundi, DRC, Tanzania, Rwanda, Malawi, the Comoros and Ethiopia, among other destinations [63]. List of pharmaceutical companies in Kenya, Nigeria, Egypt and South Africa can be found in the literature [60, 63–65]. Pharmaceutical companies in Nigeria are located in Lagos, Ogun, Kano, Imo and Anambra states. However, the activities of some unregistered pharmacies in cities like Lagos, makes the garnering of accurate data of its usage in that part of the country difficult [66]. In 2021, revenues from pharmaceuticals was forecasted by WHO [67] to reach $1400 billion. North America accounts for 49% of the revenue, Africa, 0.7%, Europe, 21.8%, Asia-Pacific, 21.7%, Latin America, 4.6%, and Turkey, Middle-East-Eurasia 2.2%. In Africa, most of the pharmaceutical industries (representing 80%) are concentrated in just 8 countries (Egypt, South Africa, Algeria, Tunisia, Nigeria, Morocco, Kenya, and Ghana), according to a 2020 report which puts their sum at approximately 600 [68]. Experts predicts a further growth (from 2020 onwards) in pharmaceutical manufacturing in Africa from a value of $40-$65 billion – a growth trend that was maintained compared to 2013’s worth of $20.8 billion [69]. Asplund [13] predicts that, the world’s medicine market may go back to pre-pandemic levels in 2022, approaching almost $1.8 trillion by 2026. Pharmaceuticals Preferably, the main role of pharmaceuticals is to influence the function of human biological elements, especially their cells and also methanogens responsible for anaerobic digestion [70]. Pharmaceuticals are generally classified into antibiotics, tranquilizers, antiepileptic, diuretics, azole (fungicide), anti-inflammatory, human drugs, analgesics, illicit drugs, blood lipid regulators, beta-blockers,

anticancer drugs, antirheumatic, personal care products (PCPs), psychotropic, cholesterol medicines, steroids and related hormones [13, 38, 71–74]. Some examples of pharmaceuticals of veterinary and human prescription, and hormones are paracetamol, rifaximin, sparfloxacin, sulfamerazine, ceftazidime, cilastatin, triclosan, β-estradiol, roxithromycin, minocycline, sulfisoxazole, androstenedione, megestrol acetate, ciprofloxacin, caffeine; chloramphenicol, clindamycin, danofloxacin, chlortetracycline, diclofenac, enrofloxacin, doxycycline, estriol, ethisterone, estrone, fenbendazole, sulfone, fenbendazole, ketoprofen, cloprop, clofibric acid, carbamazepine, ibuprofen, flunixin, florfenicol, ivermectin, marbofloxacin, lincomycin, metronidazole, ofloxacin, norfloxacin, oxytetracycline, sarafloxacin, sulfacloropyridazine, progesterone, fluoxetine, sertraline, sulfadiazine; sulfadoxine; sulfadimethoxine, clotrimazole, simvastatin, tamoxifen, sulfamethoxazole, sulfamazine, sulfathiazole, sulfaquinoxalin, tetracycline, testosterone, tilmicosin, and trimethoprim, among others [75–78]. Lincomycin (C18H34N2O6S) (LCM) is used to control gram-positive bacterial infection of human and animal and ranked second in 2012 in China in terms of consumption [61, 79]. LCM industries generates solid waste byproduct called lincomycin fermentation residues (LFR) containing residual LCM (whose concentration is around 2000 mg/ kg), mycelial cells and different organic matters which can be degraded by black soldier fly larvae (BSFL) and associated microbiota [79]. Vultures and fish are reported to be gravely affected by some pharmaceuticals. In Pakistan, a study points at diclofenac residues as responsible for reduction of vulture population in the country, while mixtures of fluoxetine, ciprofloxacin and ibuprofen in g/L concentration range results in deaths of fishes [57]. Antibiotics Production and Uses Being one of the most widely used pharmaceuticals, antibiotics occur in form of a compound or various array of molecules often channeled for the treatment and prevention of microbial infections in veterinary medicine and humans [47, 80]. In human and veterinary applications, there are about 250 different types of antibiotics [81]. Annually, China produces around 210,000 and consumes about 90,000 metric tons of antibiotics [61]. But according to Zhong et al. [17], in 2007, China produces 1.21 million tons of antibiotics, being the largest exporter and manufacturer in the world. Spain and Germany are the highest end-users of antibiotics within the European Union (EU) [82]. Hazardous waste such as antibiotic mycelial residues (AMRs) or antibiotic bioferment residues are produced in excess of 1.3 million tons in China, while 80,000 tons of veterinary antibiotics were used in 2013 in the same country [82, 83]. Consumption of veterinary antibiotics in 2013 in the United States was 11,000 tons, but global consumption of the generality of known antibiotics is still in thousands of tons [82, 84]. Mitchell et al. (2013)[85] stated that, of the 16,000 metric tons of antibiotics traded annually in the

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

country, approximately 80% are used in animal husbandry. Antibiotics are present in mixture form in the environment and are regarded as pollutants since they kill or inhibit the growth and development of microorganisms and aquatic animals [47, 86, 87]. Basically, they find applications in farming, human medicine, aquaculture and veterinary medicine, which end up in sewage or residues/excreta of poultry farms and livestock, causing heavy loses of microorganisms used in aerobic and anaerobic active sludge for effluent treatment [73, 84, 87]. Ofloxacin is an example of synthetic antibiotics widely used in aquaculture [70]. For instance, the antibiotics used as feed additives, therapeutic animal treatments, growth promoters and those used to prevent infections in pig farms can be excreted unchanged to the ecosystem [88]. This is the reason some veterinary pharmaceuticals are found in manures of some animals which contaminates the soil as well as ground and surface waters as a result of runoff from fields [89, 90]. Therefore, the digestion of some categories of antibiotic-contaminated cattle faeces or dungs is affected, as active methanogens are inhibited [91]. Few examples of antibiotics are amoxicillin, nitrofurantoin, gentamicin, rifampicin, doxycycline, tylosin, neomycin, erythromycin, sulfamethoxazole (SMX), tetracycline, roxarsone, carbadox, monensin, ofloxacin, streptomycin, flumequine, ciprofloxacin, bambermycin, apramycin, bacitracin, spectinomycin, oleandomycin, tiamulin, efrotomycin, trimethoprim, LCM and penicillin [23, 73, 92]. Erythromycin (C37H67NO13), a macrolide antibiotic that emanates from Saccharopolyspora erythraea (or actinomycete), sulfamethoxazole (SMX), tetracycline, fluoroquinolones, ciprofloxacin (CIP) and enrofloxacin (ENR) are the most widely used human and veterinary antibiotics pausing as pollution threats to the environment [31, 47, 93–95]. An original form of erythromycin derivative called clarithromycin can be discharged unavoidably to the environment through human and animal excretion as it is not absorbed or utilized fully by the patient animal or human [96]. Clarithromycin utilization doubled to 15 tons per annum from 2002 to 2009 in Germany [96]. Erythromycin and tetracycline both inhibit protein synthesis while tetracycline forms complexes with ions present or bind to soil particles, where in 2018, 25% was used in veterinary medicine accounting for 33% of antibiotic consumption in 2012 in Europe [95, 97, 98]. SMX is basically a sulfonamide (SAs) bacteriostatic antimicrobial antibiotic used to arrest urinary tract infections, as it inhibits bacterial proliferation; as well as to prevent or treat mastitis in cattle and respiratory infections when combined with trimethoprim [86, 99–101]. But SAs, tetracyclines, β-Lactams, macrolides, fluoroquinolones and nitroimidazole derivatives are the most prescribed antibiotics in animal husbandry veterinary pharmaceuticals with a share use of 90% in the UK, 77% in the EU and above 50% in Denmark and Korea [91, 97, 102]. β-Lactam residues are hardly spotted in dairy manure compared to tetracycline residues that is persistent and common [103].

SAs, lincosamide, and macrolide residues, according to the same author is typically below 1 ppb in US dairy manure samples measured. SAs utilization in Germany is up to 9% and 2-11% in Europe, among which high amount of sulfadiazine (an SAs group) was detected in chicken and pig manure [97]. Visca et al. [93] reported that, SMX (which is quite mobile) at initial concentrations of 4-20 mg/kg in the soil, would half within 4-13 days. Tetracycline kills microorganisms by terminating protein synthesis after binding to the cell ribosomes, while other sub-classes such as oxytetracycline (OTC) and chlortetracycline (CTC) helps in improving health and growth efficiency when used in animal feeds, as well as for therapeutic purposes [23, 104, 105]. Tetracycline, CTC, and OTC (first isolated in 1940s) are cheap and measured at concentrations of ≈ 5, 10, and 250 µg/kg respectively in dairy manure [23, 103]. OTC, CTC and ENR are persistent veterinary antibiotics in the environment that is used in livestock farming [23, 106]. ENR is usually administered orally to cattle or by subcutaneous injection to treat alimentary tract and respiratory infections [93]. Both fluoroquinolones and CIP has high affinity for soil and persist for several months in the environment [93]. Amoxicillin belongs to the penicillin class and can be used to treat gastro-intestinal veterinary infections [91, 107]. An oral drug known as cephalexin in conjunction with cephaloglycin is used in treating diseases caused by gram-negative bacteria [108]. The outer membrane of gram-negative bacteria makes them more resistant to antibiotics, because it thwarts their penetration into the cells compared to gram-positive bacteria [109]. However, both cubical gram positive and circular gram negative forms of bacteria are killed by amoxicillin along with anaerobic bacteria as stated by Nuengjamnong et al. [110]. Hitherto, more than 700,000 deaths per year is said to be a result of antimicrobial resistance globally, and further estimates put this figure at 10 million by 2050 [31, 77]. Practical occurrence is at Puri (Bay of Bengal), India, in which previous investigations indicates the presence of 38 multi-resistant bacteria [105]. Based on experience and as stated by Oliver et al. [103], antibiotic-resistant bacteria (ARB) are present in dairy manure. Pharmaceutical Effluent The poor biodegradability of pharmaceutical plants’ wastewater or effluent is due to large compositions of inorganic and organic toxic pollutants (such as intermediate products, catalysts, spent solvents, additives and reactants), high salt concentration and its characteristic dark color, despite having higher chemical oxygen demand (COD) and a low biochemical oxygen demand (BOD) [63, 111–116]. BOD and COD in wastewater can be determined using procedural steps illustrated by Njuguna et al. [63]. The pH of pharmaceutical effluents ranges from 4-11 while its salt content (e.g., chlorides, bromates and sulfates) could be above 1 g/L [117, 118]. Therefore, pharmaceutical industry wastewater comes from chemical synthetic plants

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

whose constituents are complex and pose serious risk to the ecosystem by inhibiting active biomass even at negligible amounts [53, 111, 119]. The high COD level in the toxic effluents is normally reduced using a chemical treatment technique called wet oxidation: which is defined as the transfer of one or more electrons from a reductant (an electron donor) to an oxidant (an electron acceptor) having higher affinity for electrons [11, 53, 120]. Otherwise, the wastewater discharged from pharmaceutical industries are difficult to treat because of the variable character the constituent toxic compounds possess [11, 121–123]. Above all, treatment of chemical synthesis-based pharmaceutical effluents involves a lot of complex operations due to formation of chemical reactions in the process [122]. Notwithstanding its characteristic high COD level, anaerobic treatment is generally favored [111]. A starting specimen for formulating commercially vital amoxicillin and ampicillin or 6-Aminopenicillanic acid (6-APA) are pollutants commonly found in the chemical synthesis and fermentation class of pharmaceutical wastewaters [107]. Others, as investigated in Kocaeli Province (Turkey) chemical synthesis pharmaceutical industry effluents by Gulmez et al. [122], are solvents such as isopropanol, methylene chloride, tetrahydrofuran, ethyl acetate, pyridine, methyl isobutyl ketone and methyl ethyl ketone, used at different production stages. Examples of wastewaters of pharmaceutical industry sources from manufacturing processes are azalide antibiotic raw water, azalide antibiotic pre-treated water, broad spectrum tetracycline antibiotic raw water, diuretic production raw water, disinfectant chlorhexidine-dihydrochloride raw water and molasses slops raw water [119]. It is however obvious that pesticides and some micropollutants are not scrutinized for potential environmental effect in the literature compared to drugs like analgesics, antituberculosis, antibiotics and antihistamines despite their utilization on the same scale [89, 124]. Environmental Contamination Pharmaceutically active compounds (PhACs), about 2300 active pharmaceutical ingredients (API) and pharmaceutical wastewaters are anthropogenic contaminants that affects human health and the ecosystems when released into the surrounding environment above certain concentrations; because they contain high COD due to the presence of organic and inorganic constituents [105, 125–128]. In such plants, wastes or effluent disposal is subject to further processing in pharmaceutical wastewater treatments plants (WWTPs), which is not often the case because half of the pharmaceutical wastewater generated globally are discharged without prior treatment as reported in the literature [127, 128]. Zhan et al. [129] describe pharmaceutical process residues (PPR) as herbal and antibiotic fermentation residues. Numerous pharmaceutical residues are practically unaffected or barely removed even after passing through WWTPs [126, 130]. In addition, non-industry pharmaceutical wastes released to the environment are as

a result of prescriptions (veterinary medicinal products) taken by humans and animals which are often excreted with faeces and urine in its original form (or parent substances) [73, 131–133]. Typical instances are the detection of LCM (7820 mg/L) in swine manures and 3 swine farms aqueous wastewaters (166 mg/L) in China due to intense application [61]. Researchers across the globe have detected several PhACs and PCPs in soils, ground water, drinking water supplies, sea water, surface water (lakes, rivers, and streams), municipal wastewater, wastewater treatment plants effluents and slaughterhouse wastewater, with detrimental effect to livestock, aquatic life and human health even at low concentrations (sludges) [50, 57, 73, 81-82, 130-131, 134-136, 137, 138,]. However, Alenzi et al. [92] attributed this to huge demands for medicines by users on daily basis. Concentrations of these micropollutants (pharmaceutical compounds) vary from ng/L to µg/L in natural water bodies and domestic effluents to up to mg/L levels in streams [77, 81, 86, 139–141]. Notable drugs or PhACs that have been detected in dirty water, soil and garbage are pivalic acid, 2-ethylhexanoic acid (2-EHA), antiepileptic drug carbamazepine (CBZ), vitamins, antidepressants, sleep aids and narcotic pain relievers to mention a few [121, 140, 142, 143]. Moreover, 80 persistent pharmaceuticals and medical substances (such as cytostatic drugs, clofibrate, antibiotics and analgesics) have been spotted in drinking water, sewage, sewage treatment plant wastewaters, surface and ground waters of about 10 countries, since 1980s as described by Nguluka et al. [57] and Fountoulakis et al.– while 200 different others are found globally in river waters according to Alenzi et al. 92]. The manufacturing, trade, storage and use of 12 persistent organic micro-pollutants (POPs) had earlier been restricted at a global treaty Stockholm Convention to safeguard the ecosystem [144]. The POPs covered are chlordane, aldrin, dieldrin, DDT, endrin, hexachlorobenzene, heptachlor, mirex, polychlorinated biphenyls, polychlorinated dibenzofurans, polychlorinated dibenzo-pdioxins, toxaphene, beta hexachlorocyclohexane, alpha hexachlorocyclohexane, chlordecone, hexabromobiphenyl, commercial octabromodiphenyl ether (hexabromodiphenyl ether and heptabromodiphenyl ether), pentachlorobenzene, lindane, perfluorooctane sulfonic acid (PFOS), its salts and perfluorooctane sulfonyl fluoride (PFOS-F). Notable PhACs Pollution Canada, USA, Brazil and many European nations found over 80 drugs in their aquatic ecosystems – UK alone detects 70 [92, 145]. This includes up to 83 ng dm–3 of paracetamol (in groundwaters) in the vicinity of Gdańsk [98]; a 1994 discovery of clofibric acid in Berlin (Germany) surface waters [146], around 0.3-19 ngL-1 concentration of clofibric acid in North Sea, and approximately 100 ngL-1 in estuaries, both in UK [105], and as well as in the 1970s in WWTPs samples in the USA [145]; 1.7g/l concentrations of antibiotics in surface waters according to United States

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

Geological Survey (USGS) [90] and; 28-31 mg/L of ciprofloxacin in India’s treated effluents and natural water bodies as well as UK, USA and Germany in the range of ng/L to g/L [57], to mention a few. Again, 3800 µg/L of metaxalone (a muscle relaxant), according to Colella [147], are found in New York’s pharmaceutical manufacturing wastewaters. Clotrimazole in concentrations ranging from 3-54 ng/L are present in Germany and UK ecosystems, as reported by Pavithra et al. [105]. The same authors also position the presence of diclofenac concentrations at around 2.3 µg/L in UK pharmaceutical effluents. Propranolol, carbamazepine and ibuprofen had contaminated Doñana Park in Spain, whereas in Warsaw, Poland, clindamycin in concentrations of 134 ng/L have been found in influents pharmaceutical treatment plants [74, 78]. According to literature, analysis of dams, hospital effluent and sachet waters in Nigeria shows the presence of some antibiotics in alarming proportions. Usuma dam [148], which delivers treated water to Nigerian capital territory for instance, contains metronidazole, trimethoprim, ciprofloxacin, ibuprofen and amoxicillin whose risk levels are classified into low, medium and high to aquatic species, according to Ilechukwu [149]. Previous reports show high proportion of amoxicillin (8066 µg/L) in Sango Ota, Ogun state in Nigeria which has few pharmaceutical companies and whose population largely depends on the antibiotic [150]. Similar studies reveal the presence of

Method

Biogas: 289.90 mL gVS−1 untreated & 27.6% more after pretreatment

Serum bottles Spectinomycin mycelial residues of and not standard 265 mg L−1 reactor types was used

Production of gas Methane: 22.5 L d–1 Spent mycelia + in 10 days only Corn-grass silage + forced-stopped by Pig slurry an inhibitor

Biodegradability Of Antibiotics Contaminated Manure

Since 1990s, the anaerobic digestion of synthetic drug based effluents and antibiotics had been studied by various researchers using sulphate reducing organisms, iron reducing organisms, methanogenic organisms and nitrate reducing organisms [204, 249]. Before the AD of waste of pharmaceutical origin, their toxicity and biodegradability should be determined in advance for appropriate selection of a suitable operational parameters, as some antibiotics promote AD performance at certain conditions [131, 250251]. In essence, low drugs concentration positively inhibits biogas yield whereas high drugs concentration stimulates the process [145]. So, it affirms the reason why some antibiotics, PCPs and chemical/pharmaceutical wastewaters are inhibitory, toxic and hard or partially degraded as they affect methanogen’s growth and physiology and the efficiency of the process [131, 252, 253]. Typically, carbamazepine, diclofenac and tramadol, based on the SMA, is likely to be stimulating at low concentration while carbamazepine at high concentration – bearing similarity with ciprofloxacin which can either be stimulatory and non-stimulatory at high or low amounts [93, 145]. Such inhibitory properties of antibiotics on methane and biogas synthesis are due to pH reduction, dissolved COD and volatile fatty acids (VFAs) accumulation; such as large accumulation of VFA during AD of 45-50 mg/L of SMX [93, 250]. For example, antibiotics like chloramphenicol, neomycin, tylosin, doxycycline, chlortetracycline and streptomycin caused slight inhibitory effect on CH4 production while erythromycin concentration of up to 250 mg/L, linear alkylbenzene sulfonate (LAS) and carbamazepine (CBZ) did not inhibit biogas generation according to literature [111, 142, 249]. Similarly, amoxicillin (60 mg/L) reduces the cumulative biogas and CH4 production by 25%; tetracycline

and sulfamethoxazole mixture (0.5–15 mg/L) and penicillin inhibits AD by 25% and 35% respectively in an ASBR; chlortetracycline reduces CH4 production by 20% when fed to pig and; oxytetracycline strongly inhibits AD completely, except at concentrations around 250 mg/L in some cases [90, 102, 110, 141, 249]. On the other hand, Azizan et al. (2021)[141] found that an 8.5 mg/L concentration of tetracycline in pharmaceutical effluents totally inhibit CH4 production. Stergar & Konèan [251] states that, equipment selection for anaerobic treatment of certain waste depends on the nature of the substrate and the process limiting steps. Sulfamerazine in pharmaceutical wastewater, as an example was found to be biodegradable and only inhibit methanogenesis at threshold concentration of 90 mg/L in a UASB bioreactor as reported by Li et al. [111]. Also, heavy metals and pharmaceuticals removal from pharmaceutical effluent sludge using steam explosion pretreatment method was found to improve its biodegradability and biogas yield (up to 380 mL CH4/gVS) when pretreated at 10 bar for 15 minutes [254]. The AD technology offers reliability in treating animal manure, tannery waste, textile, distillery, personal care products (PCP) and both low- and high-strength pharmaceutical industry wastes, as it needs low energy compared to aerobic process which offers a decrease in biomass yield [186, 189, 255–257]. To address the disparity, Iliopoulous et al. [156] explored the joint use of anaerobic MBBR and aerobic MBR for pharmaceuticals removal and municipal wastewater treatment. PCPs such as diclofenac and contraceptives in soils are non-biodegradable and affect live organisms in the ecosystem (the case of reproductive failure in fish caused by 17-α ethinylestradiol) [72, 78, 92, 258-259]. According to Omil, et al. (2007)[258] reports, AD of PCPs have earlier been studied in sewage sludge. Even though antibiotics in animal waste pose significant side effects during their digestion, AD remains the most efficient way of treating antibiotic-contaminated livestock wastes [250]. Antibiotics (e.g., ampicillin, oxytetracycline, tylosin, chlortetracycline, florfenicol and sulfamethazine) are often spotted in cow and pig manure [85, 102, 250]. Oxytetracycline and chlortetracycline in pig manure, for instance, decreases

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

CH4 production during AD by 56-62% while at mesophilic conditions, oxytetracycline in cow manure reduces biogas production by 60% [250]. Gaballah et al. [260] mentioned that the veterinary antibiotics present sometimes in mixed form in manures, can be removed before its AD. Nesse et al. [261] reported that the edible mushroom grown on PPRpolluted biogas digestate led to the uptake of the pharmaceuticals present in it in low amounts. Medical and Pharmaceutical Sludge Digestion Literature studies shows that pretreated medical cotton industry wastes, after 90 days fermentation yields 26.916 mL/gVS and 51.622 mL/gVS of biogas at respective mesophilic and thermophilic temperature regimes [262]. Biogas plants in the past 10 years have been constructed near healthcare facilities in Madagascar, Nepal and Tanzania by the Health, Environment and Climate Action Foundation

of Nepal and the HCWH [263]. Based on digestion carried out by Dhakal et al. [247] for 147 days in Bir Hospital (established in 1889), Kathmandu using a 21m3 digester, 95 kg/day of mixed healthcare waste produced 5.78 m3/day of biogas. In an experiment carried out by Mohammed et al. [207] and Kabbashi et al. [209], three Red Blood Cells (RBCs) samples (A: 446.4g RBC with TS = 22.4% operated at 31.57°C for 150 days produces 1470 mL of methane gas, B: 348.4g RBC with TS=28.7% operated at 29.44°C for 110 days produces 2625 mL of methane gas, and C: 348.4g RBC with TS=28.7% operated at 29.25°C for 90 days produces 304 mL of methane gas) and two whole blood samples (D: 274g RBC with TS=36.5% operated at 29.25°C for 20 days produces 3075 mL of methane gas and E: 274g RBC with TS=36.5% operated at 29.89°C for 20 days produces 2570 mL of methane gas) were used at Khartoum, National

Figure 3. Biogas plants for ad of medical and pharmaceutical waste/effluents [From Stringer, Avadhani & Rege; i.e., [263, 266-267], with permission from GPP, Embio Ltd. & IBA].

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

Centre for Energy Research (NCER) to assess the methane gas yields of biomedical wastes. Dextran pharmaceutical effluent released from Xinlun Pharmaceutical Factory in Jianyang City, China yields 215.85 L/kgCOD of biogas after 28 days in a 635.5 liters of plexiglass digester according to Xu et al. [30]’s findings. Huang et al. carried out AD of 3 kg of dextran contained in activated sludge at 21-33°C for 42 days yielding 201.77 litres (13.31 L/kgCOD) of biogas when there was no mixing and 381.60-455.05 litres (19.81-21.07 L/kgCOD) when mixing was involved in a 750 liters biodigester. Findings of Gustavsson et al. [264] shows that 180 mL/gVS of CH4 is produced by digesting industrial sludge from Björkborn industrial area in Karlskoga polluted with explosives, nitroaromatic compounds and pharmaceutical residue – whereas co-digestion of the same sludge with oat gives 270 mL/gVS of CH4. Meanwhile, Yin et al. [164] produced 499.46 mL/gTS of biogas from pharmaceutical sludge at 10.32 inoculum-to-substrate ratio. Adesina & Felix [98] reported that diclofenac was biodegraded only at sludge retention time of 8 days minimum. There was 20.8% improvements in CH4 generated when anaerobic granular sludge and anaerobic suspended sludge was digested with 1000 mg/L LCM. Biogas yield and CH4 content during norfloxacin and tetracycline distillery wastewater purifications are 191 cm3/g and 254 cm3/g and 70% and 67% respectively [87]. Currently, addition of zero valent iron (ZVI) and granular activated carbon (GAV) to improve AD of pharmaceutical wastewater had been studied [265]. Practical applications of medical and pharmaceutical digesters for biogas production are shown in Figure 3. Embio Limited, India, converts molasses into drugs intermediate by fermentation which in turn generates substantial amount of waste with biogas potential. Thus, a fixed film digester anaerobically digest the 300 m3/day of wastewater generated at 50-55°C (& pH=7.2), and yields 1450015000 m3/day of biogas which is rerouted to boilers through gas blowers to generate steam for reuse [266]. Also in Figure 1c, Anthem Biosciences Private Limited treats thick slurry fermentation waste broth (pharmaceutical effluent) from tetrose, peptone, soya flour and cultures as raw material to produce 2250-2500 m3/day of biogas [267]. Biogas from Herbal Pharmaceutical Waste India has witnessed rapid growth and development in the manufacture and use of herbal pharmaceutical products to treat diseases, while in Poland, the country is regarded as a major herbs producer in Europe between 2012- [192, 268]. Agricultural outputs such as herbs has also been used to formulate pharmaceutical products some of which (real herbs or herbal industry wastes and effluents) can be used to produce biogas and bio-slurry, as they are characterized by high organic content [269, 270]. Justicia schimperiana (JS), lemon balm and alder buckthorn are typical examples of herbs or herbal industry waste that has been used as biogas substrates as well as medicinal plants like Glycyrrhiza glabra (GG), Mentha, Cuminum cyminum (CC), Lavender

and Arctium [268, 271-272]. Some of these pharmaceutical herbs are characterized with unpleasant smell and high composition of organic pollutants [192, 272]. GG and CC of 10% TS, produces 13471 mL and 13611 mL of biogas after digesting 250g each of the plants in batch reactors at 35°C, according to results obtained by Fardad et al. [271]. Findings from experiment conducted by Czubaszek (2019) [268], shows that alder buckthorn and lemon balm produces 386±33 and 461±23 NL kgVS-1 of biogas within a 35 days retention period. Patel et al. [273] stated that the biogas potential of herbs is naturally favoured by their high organic matter content. Also, from the Laboratory of Ecotechnologies (the biggest biogas lab in Poland), biogas produced is 172.18 m3/Mg FM (or 526.23 m3/Mg TS) at pH of 5.4, from a herb of 32.70%TS and 90.13 %VS [274]. Peni et al. [41] recorded 169.4 NL/kgVS and 193.2 NL/kgVS of biomethane from the perennial plant called Helianthus salicifolius – from raw biomass and silage respectively. Human Urine Digestion Between 70-90% of antibiotics are usually released in their original form via urine and feces [275]. Human urine with pH ranging from 4.8-7.5 contains 99.6% water and 0.4% dry matter, in addition to 2% w/w urea that is readily hydrolyzed to CO2 and NH3 [21, 276]. According to Kim et al. (2020)[276], an average human produce 1.4 liters of urine that contributes 50% of phosphorus and 85% of nitrogen in domestic sewage. Accordingly, Haque & Haque [21] shows that mineral nitrogen fertilizer in Sweden have similar effect on plant growth compared to human urine. Mono- and co-digestion of urine with other substrate have also been studied by researchers. For instance, the ratio, “cow dung : human urine : water” (50:10:40) generates 43.42 litres of biogas while 1:1 ratio of human urine and cow dung produces 41.95 liters of biogas at 28-35°C [21]. In another studies, the addition of 250 mL urine to 100 g of boiled rice produced maximum CH4 and biogas [277]. A practical approach towards generating electricity and cooking gas from biogas plants to be constructed by Lumos Laboratories Nigeria Limited was made by the Federal Government recently, which would be adopted at prisons across the state. The plants would use human urine at correctional centers in the country and was pioneered by Nwosu (Patent No. NG/P/20/2013/699) in 2014 [278]. Kinetics and Optimization of Biogas Production In the literature, kinetics of biogas production from medical and pharmaceutical wastes is scanty. This study identifies the Monod, Haldane, Andrew, Modified Gompertz, modified Stover-Kincannon and Van der Meer and Heertjes kinetic models as some of the mathematical models for optimizing AD and biogas production associated with pharmaceutical wastewater as feedstock [191, 279–281]. The Andrews’ kinetic model is a concentration-dependent process designed to biologically eliminate and reuse liquid toxic waste. The model is best suited for

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

pharmaceutical waste/wastewater digestion at low substrate concentration, because at high concentrations, toxicity and inhibitory effects are seriously felt [53]. In numerous occasions, there is no proportionate relationship between the inhibitory effect and the inhibitor concentration on the kinetics, hence a non-linear function (modified propionate and acetate consumption model) to study the inhibition of pharmaceuticals on both acetogenesis and methanogenesis can be used [70]. Amin et al. [90] examined the effect of high OTC loadings on acidogens and methanogens using Haldane inhibition kinetics, where they realized that an increase in toxicity at increasing loading rate signifies a decrease of the Haldane inhibition constant. Though the Monod equation does not explain possible inhibitions in AD systems involving pharmaceutical effluents, the model can be applied while studying the kinetics of biogas production using biodegradable pathological waste. Equation 1, 2, 3 and 4 are the Monod, Andrews’, the propionate and acetate consumption rate and Haldane kinetic models [53, 70, 90]: (1)

(4) where, µ = specific growth rate of biomass (/day), µmax = maximum specific growth rate of biomass (/day), S = biodegradable pollutant (substrate) concentration (mg/L), KS = half saturation coefficient (mg/L), KI = inhibition coefficient (mg/L), rmodified = propionate or acetates consumption rate, I = concentration of the pharmaceutical and m = constant representing the non-linear dependence of inhibition (when m = 1, the inhibition reduces to non-competitive type; when m < 1, inhibitory effect on the kinetics tends to be insensitive with inhibitor concentration and; when m > 1, inhibitory effect on the kinetics tends to be very sensitive with inhibitor concentration). Human and animal urine from patients at medical centres are typical example of biogas substrates containing inhibitors since they are released unchanged from the sick organism consuming pharmaceuticals. Optimization of biogas production from urine can be carried out using Equations 2 and 3 if the patient animal is known to consume antibiotics and other inhibitory drugs. Nevertheless, such studies is still lacking, kinetics of biogas production using non-contaminated urine has

been analyzed by Sau et al. (2013)[277] using the Chen and Hashimoto model.

Waste Management Practice

In this work, three types of waste have been identified, namely, chemical, medical and pharmaceutical wastes. Before the detection of pharmaceuticals in the aquatic environment, they have been detected on land and studied since the 1970s [66]. In water bodies, many are described as pseudo-persistent, i.e., relatively having short half-lives in the ecosystem with notable effect to humans such as reproductive damage, cell inhibition and behavioral changes [92, 98]. However, they are unlikely to cause significant harm on land (waste of hospital, landfill, agricultural, graveyards and industrial pharmaceutical activities), because they occur at very low concentrations; based on few research conducted to ascertain their toxicity to the ecosystem [75, 92, 131]. Pharmaceutical waste are simply contaminated, prescribed, expired, spilt, vaccines, sera, and propriety drugs and unused pharmaceutical products which is no longer needed and so is disposed off [139, 207, 282]. Unused medications could cost billions of dollars globally, and according to a US report, more than 50% of patients stores unused and expired drugs in their homes which they end-up flushing down the toilet [98, 283]. While studying 427 households in Nigeria, Auta et al. [283] found that 94.1% of households keep unused medicines either for re-use or serve another sick household member with ‘probably’ a similar medical issue But elsewhere (Lagos), out of 376 healthcare workers, 40.4% returned unused drugs, 41.2% returned expired ones to manufacturers and 19.9% return it to sellers according to a survey carried out by Adesina & Felix [98]. Reasons resulting in unused drugs are change in treatment plan, recommended drug is inappropriate for the need, non-adherence to therapy, medications reaching expiry dates, supply of unwanted quantities, adverse drug event, over prescribing, and nonrecognition of drugs due to a foreign label [283, 284]. In Lagos, Nigeria, absence of proper disposal guidelines for unused medication according to global best practices and a non-return policy (which is only 22.9% according to a US report but a predominant practice in Sweden) are challenges to address [98, 285]. Individuals and households, as a common practice, dispose medicines in garbage; especially in countries like Lithuania, United Kingdom and Kuwait [285]. A study of a pharmacy in Kuwait shows 73% of the respondents use trash to dispose unwanted medicines, 38.6% of doctors in South India dispose pharmaceuticals in dustbin and 24.6% flush them down the sink, a method commonly practiced in the US, and 59.7% of the 22 wards studied in Maiduguri, North-Eastern Nigeria dispose expired drugs using household garbage [98, 285]. Unprofessional disposal of expired pharmaceuticals (e.g., landfill and water bodies) had previously resulted in deaths and medication poisoning in scavengers, children and adult, whereas those emptied into

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

sewage systems kills bacteria responsible for its treatment [140, 284]. For example, waste drugs could be stolen from storage and sidetracked to the market for misuse and resale [284]. In Nigeria, non-prescribed drugs such as antihypertensives, analgesics, antimalarials, antibiotics, steroids, antacids, anticonvulsants, and antihistamines are highly consumed [66]. Management of chemical and biomedical waste is also a thing of concern. Chemical waste materials entails hormones, antioxidants, plasticizers, detergents, insecticides, pesticides, fire retardants, disinfectants, human and veterinary drugs that originates from homes, agricultural applications, dental, medical, veterinary laboratories and industries [7, 38, 89]. Biomedical waste as explained earlier, emanates as a result of diagnosis, immunization or treatment in medical or research facilities which are categorized into bio-hazardous and non-hazardous waste with characteristic high BOD content (about 234 ppm in Nigerian hospital sewage) [226, 286, 287]. For instance, about 26.5% of waste produced in 5 healthcare institutions in Nigeria’s capital territory is hazardous medical waste based on a 2006 study [214]. Fundamental data regarding medical waste disposal emerging from hospitals is not available in Nigeria and the responsibility for its disposal is not assigned to anyone nor is it clearly defined [236, 283]. Except for Lagos in Nigeria, that at least constructed several highly-equipped transfer loading stations at strategic locations in the state [288], as shown in Figure 4. Previously, moves have been made by the American Hospital Association (AHA) and the Environmental

Protection Agency (EPA) in 1998 to reduce health care waste volume from 2005-2010, and in 1980 in Malaysia, clinical waste management began in the country [225, 286]. As a solution to menace posed by medical and pharmaceutical waste, Nyaga et al. [289] suggests the lessening of pharmaceutical waste generation, its collection at designated sites (e.g., Figure 2), implementation of a take-back options, application of recent technology and the lunching of public awareness campaigns together with policies and guidelines for a safe disposal. But in developing African countries, especially Nigeria, only few are well informed about the dangers posed by medical waste to the environment – specifically, in Tripoli, Libya, out of 300 medical waste handlers surveyed, only 7% had received training vis-à-vis its handling [228, 239]. In addition, zero training was given to medical waste personnel in Serbia while only 23% received such training in Bangladesh [228]. But surprisingly, in North-Eastern Nigeria, and based on Okoro & Peter [285]’s survey, more than 80% of the people knew the impacts of improper discarding of medicines to public well-being. Currently, a company based in Amsterdam (Pharmafilter), has developed a technology that digest biodegradable hospital waste anaerobically, thereby combating antibiotic resistance and in turn uses the biogas generated to power itself, as shown in Figure 5. The use of the Pharmafilter technology would however be based on the time bound planning (scheduling) of various waste management steps of segregation, collection, storage, treatment to disposal [1, 229]. It is worthy of note that segregation is best practiced at place of waste

Figure 4. Special containers for loading medical waste at a transfer loading station in Lagos, Nigeria [From Awodele et al. [288], with permission from BMC Public Health].

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

Figure 5. Anaerobic digestion of hospital waste in Amsterdam, Netherland. [From Burik [213], with permission from LABIOTECH]. generation (usually the medical arena) by physicians, technicians and nurses [227]. In Africa, Indonesia and Korea, mixed waste containing hospital and municipal waste are commonly found in waste streams, bins, residential waste landfills and road sides [228, 288]. At present, Nigeria has no planned time scheduled healthcare waste management system and only 16.9% of health facility waste had been reported to be segregated in Lagos [229, 236]. Furthermore, syringes and other medical waste are regular contaminants

of beaches of Bali in Indonesia [228]. Figure 6 shows medical waste being separated from non-medical waste at a hospital at Tamil Nadu, India. Waste management practices for medical, pharmaceutical wastes and pharmaceutical process wastewater are inertization, deep burial, waste immobilization, microwaving, encapsulation, secure land filling, burning and incineration [98, 240, 290]. Honkanen [291] carried out a feasibility assessment on incenerating medical waste in South-Asia.

Figure 6. Segregation of medical from nonmedical waste at Christian Medical College, Vellore, Tamil Nadu, India [From Thomas et al. [153], with permission from IJERT]

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

Incineration is a high temperature (600-1200°C) thermal process that combust waste to gases and inert materials [7, 238]. Controlled air, rotary kiln and excess air incinerators are the three main kinds of incinerators [208]. Novel incinerator technologies are foundries or coal-fired thermal power stations and cement kilns (suited for expired pharmaceuticals) that disperse unwanted gases through tall chimneys [208, 284]. Sometimes these incinerators are made of bricks, especially the De Monfort incinerators [292]. Open burning at low temperatures and incineration release carcinogenic toxic chemical products called furans and dioxins that pollutes the air, thereby causing respiratory illnesses and cancer, as well as residual ashes [7, 209, 212, 284]. Apart from residual ashes, dioxins and furans, incinerators are sometimes left with needles, blades, heavy metals, polycyclic aromatic hydrocarbons (PAHs) and other sharps [3, 209, 238]. China has the highest dioxin emission threshold (5 ng/m3) than the majority of European nations [209]. Nevertheless, incineration remains the most extensively used technique of treating hospital waste in numerous places around the world [7]. In Africa, Ethiopia, Botswana, Algeria and South Africa use incinerators: Tanzania in recent past constructed 13 pilot small scale incinerators [216]; in Ibadan, Nigeria, only few hospitals use incinerators [226]; and inadequate incineration practices in Tunisia is responsible for 90% of dioxins and furan emissions [229]. Six out of nine private healthcare facilities in Iran having incinerators, face mild operational problems; Korea is witnessing an insufficient controlled practices; incinerators in Malaysia are meant for hazardous and infectious waste treatment and; 67% of hospitals incinerate their infectious waste in the US [225, 226, 228, 288]. Hitherto, it took Eritrea 6 months to burn 7 truckloads of expired aspirin tablets; the act of burning unused and expired medicines at home is commonly practiced in Lithuania; while in Ibadan, Nigeria, approximately 30% of hospitals apply the open burning process [226, 284, 285].

close proximity to hospitals in some countries. However, incineration and open-burning remains the most applied waste management practice at the moment with attendant harmful effect to humans. Construction of biogas plants is therefore encouraged to digest biodegradable pharmaceutical wastewater and medical waste, because it is safer than the combustion processes. Findings show that degradation of pharmaceutically contaminated effluents produces less biogas and requires longer retention times of more than 100 days due to the presence of negligible biodegradable matter or inhibitors. In Sudan, 1470-3075 mL of methane has been obtained from blood biodigestion. Around 2.5m3 of biogas has been obtained by degrading placenta at Mwananyamala hospital in Tanzania and 5.78m3/day of biogas has been obtained through the decomposition of pathological waste near Bir Hospital, Nepal. Existing gaps that need to be filled is the practical and purposeful construction of a multipurpose bioreactors (either conventional or nonconventional/membrane reactors) for large scale treatment of pharmaceutical, medical and associated effluent with a biogas and biofertilizer recovery system. Extensive review of literature has shown that such practices are often done at laboratory scale using nonconventional reactors with just few efforts made to recover the potential bioenergy inherent in the wastes. Separation technologies such as liquid-liquid extraction and distillation is recommended where the end-product of the wastewater treatment setup is to produce drinkable water. To sum it up, a biogas or bioenergy recovery system from pharmaceutical, herbal and medical waste has the potential to address environmental pollution, energy security, efficiency, health of (would be affected) humans and animals and unemployment challenges. Chemical or biochemical engineers and biotechnologist should therefore study the kinetics inhibiting anaerobic digestion of some pharmaceutical wastes/ effluent in order to discover ways to optimize useful product recovery or suppress their effect during treatment.

Acknowledgement

Influence of wastes from pharmaceutical industries and medical health centers on the environment is a thing of concern to safeguard the habitat. Researchers are currently looking at ways to dispose or decompose these wastes and their effluents by transforming them to bioenergy or biofuel source by harnessing their unique characteristics. The market for pharmaceutical industry is growing and has witnessed skyrocketed increase in drug mass production due to recorded spread of infectious diseases occasioned by the famous Ebola and COVID-19 virus worldwide. This has also added to the amount of waste emerging from hospitals globally. Though not all these wastes are biodegradable due to their inhibitory or toxic nature, researchers and environmental management experts are constantly trying their luck to produce biogas from both pharmaceutical and medical waste, and had attempted to build biogas plant at

Part of this manuscript had been presented in AL-FARABI 4th International Congress on Applied Sciences (Erzurum, Türkiye) between August 19-20, 2022. The organizers are acknowledged for accepting the Abstract and providing the corresponding author the opportunity to present the write-up.

Data Availability Statement

The authors confirm that the data that supports the findings of this study are available within the article. These data are cited accordingly and can found amongst the list of bibliographies used.

Sigma J Eng Nat Sci, Vol. 42, No. 4, pp. 1261−1291, August, 2024

Conflict Of Interest

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics

There are no ethical issues with the publication of this manuscript.

Share and Cite