Journal of Xenobiotics 2016; volume 6:5774 Pharmaceutical compounds about 1 lakh ton/year. This data reveals the worldwide average consumption of 15 gm/capi- Correspondence: Bhavtosh Sharma, Uttarakhand in drinking water ta/annum.1,2 The large diversity of the human Science Education and Research Centre pharmaceuticals may be noticed by 12,000 (USERC), Dehradun, Uttarakhand, India. Vikas Chander,1 Bhavtosh Sharma,2 approved (authorized) human pharmaceuti- E-mail: [email protected] Vipul Negi,3 Ravinder Singh Aswal,4 cals. From environmental consideration, there Prashant Singh,1 Rakesh Singh,3 Key words: Pharmaceutical effluent; pharmaceu- are 850 active compounds in human pharma- tical global market; fate and water pollution. Rajendra Dobhal5 ceuticals.3 India has now emerged as one of the top five pharmaceutical markets of the 1Department of Chemistry, DAV (PG) Received for publication: 22 January 2016. world. As pharmaceutical industry is the lead- Revision received: 21 April 2016. College, Dehradun, Uttarakhand; ing science based industry in India, thus it Accepted for publication: 25 April 2016. 2 Uttarakhand Science Education and contributes 1% of the country’s total gross Research Centre (USERC), Dehradun, domestic product.4 Due to regularly increasing This work is licensed under a Creative Commons Uttarakhand; 3Department of Chemistry, international demand, pharmaceutical indus- Attribution NonCommercial 4.0 License (CC BY- NC 4.0). DBS (PG) College, Dehradun, tries are rapidly growing. This development of 4 Uttarakhand; Department of the pharmaceutical industries supplies over 65 ©Copyright V. Chander et al., 2016 Environmental Sciences, Gurukula Kangri countries and earns more than 50% revenue Licensee PAGEPress, Italy Vishwavidyalaya, Haridwar, Uttarakhand; through exports.5 United States of America is Journal of Xenobiotics 2016; 6:5774 5Uttarakhand Council for Science and the largest customer of Indian made drugs, doi:10.4081/xeno.2016.5774 Technology (UCOST), Dehradun, which procured drugs worth Rs. 1.4 billion US 6 Uttarakhand, India dollar during the year 2007. The pharmaceuti- cal industries consist of approximately 300 large scale and 8000 small scale organizations, ceutical units are running in India and China, 15 producing thousands of formulations contain- respectively. However, the production of phar- ing 350 different bulks of drug.4 Many pharma- maceuticals at global level as per continent Abstract ceutical manufacturing units are rapidly wiseonly is shown in Figure 1. India has progres- increasing in India,7 which dispose-off their sively producing and consuming the pharma- ceutical drugs.16 According to a recent Indian Pharmaceutical products and their wastes effluents into the stream either directly or report, the Indian pharmaceutical market is play a major role in the degradation of environ- after partial treatment. Therefore, proper man- expected to be US $ 55 billion by the year 2020 ment. These drugs have positive as well as agement along with complete and useeffective 17 negative consequences on different environ- treatment of pharmaceutical industrial wastes among all third world countries. The mental components including biota in differ- as well as of expired drugs is required to be European Federation of Pharmaceutical 18 ent ways. Many types of pharmaceutical sub- undertaken with latest tools and techniques. Industries and Associations (EFPIA) shows stances have been detected with significant The pharmaceutical drugs get excreted with that Switzerland is the largest producer of concentrations through various advanced urine and feaces as parental compound and as pharmaceutical drugs in European continent. instrumental techniques in surface water, sub- a number of its metabolites. The waste water It produces pharmaceutical drugs worth 32,380 surface water, ground water, domestic waste of toilet is subsequently flushed with clean million €. Whereas, Latvia has the lowest pro- water, municipal waste water and industrial water, which is known as black water. This duction of these drugs worth only 108 million effluents. The central as well as state govern- black water enters to the municipal sewer and €. The Cyprus has market value and export of ments in India are providing supports by creat- ultimately enters the adjoining water bodies only 203 million € and 223 million €, respec- ing excise duty free zones to promote the phar- and may affect the water quality and aquatic tively. While, Germany has highest market maceutical manufacturers for their produc- commerciallife.8 The water pollution due to pharmaceuti- value and export of 26,122 million € and tion. As a result, pharmaceutical companies cal wastes in Andhra Pradesh (India) has been 50,818 million €, respectively. Similarly, the are producing different types of pharmaceuti- reported to be about 150 times more than the Belgium has imported pharmaceutical drugs of cal products at large scale and also producing highest level of pharmaceutical pollution in 26,757 million €. While, Cyprus has imported complex non-biodegradable toxic wastes by- USA.5,9-14 However, very few studies on pharma- drugs of 237 million €. The statistical graph as products and releasing untreatedNon or partially ceutical based water pollution have been car- depicted in Figure 2 represents country wise treated wastes in the environment in absence ried out in India. The present paper highlights position in terms of production, market value, 18 of strong regulations. These waste pollutants and reviews the impact of pharmaceutical pol- import and export respectively. In 1947, the are contaminating all types of drinking water lutants on quality of water sources. turnover of registered Indian pharmaceutical sources. The present paper focuses on water industries was Rs. 10 Crore. Now, it has quality pollution by pharmaceutical pollutants, increased up to US $ 5.5 billion in 2004 with 19 their occurrences, nature, metabolites and 17% annual growth rate. their fate in the environment. Global pharmaceuticals market status Route of entry of pharmaceuti- Globally, the developed countries are main Introduction producers of pharmaceutical drugs. The five cal compounds into water system major countries in the world namely USA, The utilization of pharmaceutical drugs Japan, Germany, United Kingdom and France Pharmaceutical substances are widely used keeps rising due to improvement in health are collectively two-third global pharmaceuti- for human and veterinary related health prob- care system and expectations of people for cals manufacturers, while China and India are lems. More than hundreds of tonnes of phar- longer life. The global utilization of different main global low cost producers of pharmaceu- maceutical compounds are used in Austria, pharmaceutical drugs by human beings is ticals. Approximately 20,000 and 7500 pharma- England and Germany collectively.20 According [Journal of Xenobiotics 2016; 6:5774] [page 1] Review to an investigation, the consumption of phar- efficiently removed from aqueous phase of maceuticals i.e., 836 ton of acetylsacylic acid Fate and occurrence of phar- waste water in a water treatment plant [non-steroidal anti-inflammatory drugs maceuticals in environment through several processes namely bio-degrada- (NSAIDs)], 622 ton of paracetamol (NSAIDs), tion, sorption, stripping to air and abiotic 517 ton of metformin (antidiabetic), 345 ton of transformation (photolytic degradation). ibuprofen (NSAIDs), 88 ton of carbamazepine The distribution of pharmaceutical products Complete biodegradation, which results into (antiepileptic) was found in Germany, where in the environment is mainly by aquatic medi- carbon dioxide (CO2) and water (H2O) is called as 35 ton of naproxen (NSAIDs) was observed um followed by food-chain dispersal due to mineralization. Incomplete or partial biodegra- in England in year 2001.21 But due to incom- their low volatility.20 Although pharmaceuticals dation includes the conjugation of the pharma- plete metabolism these drugs excrete through persist low in environment, they are ubiqui- ceutical and the degradation of a compound to defecation and urinary systems as unchanged tous in environment due to their higher rate of a metabolite (also occurs in the human body). form and still remain in sufficient concentra- release as compared to the rate of transforma- Conjugations of pharmaceuticals occur usually tion level. The discharge of treated, partially tion.30 Composition of sewage, weather condi- before excretion from human body. Due to treated and untreated effluents of pharmaceu- tions, design and operation of treatment plants this, compound becomes more polar and might tical industries in open areas as well as into determine the transformation of various active excrete more easily from body.8 Ibuprofen, the streams22 and unacceptable dispose of pharmaceutical products.31 The pharmaceuti- reached in the aquatic environment through unused (i.e., expired drugs) ultimately con- cal products contaminated sludge, when used metabolic process, has been studied by many taminate various compartments of environ- as an agricultural fertilizer can reach to the researchers. The metabolism of ibuprofen ment.23,24 These pharmaceutical residues may terrestrial environment and through chain it leads to the formation of hydroxyl-ibuprofen enter: i) in water supplies and soil through the may enter into surface as well as ground (OH-Ibuprofen), carboxy ibuprofen (CA- 32 excretion of animals and human beings: ii) in water. Pharmaceutical compounds