Environment, Development and Sustainability (2022) 24:12446–12466

https://doi.org/10.1007/s10668-021-01948-2

CASE STUDY

Comparing the environmental impacts of paracetamol

dosage forms using life cycle assessment

Rachit Kumar Sharma1 · Geo Raju1 · Prabir Sarkar1 · Harpreet Singh1 · Ekta Singla1

Received: 21 May 2020 / Accepted: 30 October 2021 / Published online: 18 November 2021
© The Author(s), under exclusive licence to Springer Nature B.V. 2021

Abstract
A medicine can be administered in varied dosage forms which are having different environ-
mental impacts. Two dosage forms of paracetamol (tablet and syrup) have the same func-
tion but are prepared and packaged differently, meaning that the environmental impacts
arising out of their production will be of different magnitude. This study utilizes the life
cycle assessment technique to find and compare the environmental impacts of two dosage
forms of the paracetamol. Life cycle assessment software ‘GaBi’ v 8.0 has been utilized
to carry out this study. Midpoint and endpoint impact assessment methods from ‘ReCiPe’
impact assessment method are used to carry out the life cycle impact assessment. The
midpoint impact assessment results show that syrup production has 90% contribution in
climate change impact category and more than 50% environment impact in fine particu-
late matter formation, fossil depletion, freshwater consumption, freshwater eutrophication,
freshwater ecotoxicity, ionizing radiation, photochemical ozone formation, stratospheric
ozone depletion, and terrestrial ecotoxicity midpoint impact categories. Tablet production
has major impacts in 3 midpoint impact categories that are human toxicity, ionizing radia-
tion, and metal depletion. Syrup production has major impacts (more than 70%) in 8 out of
the 11 endpoint impact categories considered, while tablet production has a major impact
in 3 impact categories that are human toxicity and ionizing radiation endpoint impact cat-
egories. Syrup production has a visibly higher impact in more number of midpoint as well
as endpoint impact categories considered. The environmental hotspot is, however, depend-
ent on the individual impact categories. The results of the study add to the existing knowl-
edge of environmental sustainability assessment in the pharmaceutical sector and will
benefit the environmental managers to better manage the environmental sustainability of
pharmaceutical products.

Keywords Sustainability · Manufacturing processes · Paracetamol tablet · Paracetamol

syrup · Dosage forms · Environmental impacts

* Prabir Sarkar
prabir@iitrpr.ac.in
1
Department of Mechanical Engineering, Indian Institute of Technology Ropar, Rupnagar,
Punjab 140001, India

1 Vol:.(1234567890)
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1 Introduction

The industrialization has led to increased extraction of natural resources from Earth, lead-
ing to their rapid depletion. This has led to an adverse effect on the environment (Lin-
ton et al., 2007). Industries produce emissions when they produce the products from the
extracted natural resources. These emissions may be solid, liquids, or gases. These emis-
sions disturb the ecosystem of the nearby area in which they are located, as well as the
whole Earth. For example, certain gases like carbon dioxide, methane, etc., when released
into the atmosphere, increase the temperature of the Earth on account of their global warm-
ing potential (GWP). There are emissions at each level of the supply networks of products,
beginning from the raw material extraction, processing of raw materials, production of
parts, assembly of parts, packaging, distribution, and disposal (Kloepffer, 2008). Assess-
ing and improving sustainability in manufacturing organizations requires the study of their
supply networks. Sustainable supply networks and their design have its origins in the start
of use of the life cycle assessment (LCA) approach to assess the environmental impacts of
products by environmental managers.
The pharmaceutical industry is investigating many approaches to mitigate its environ-
mental impacts (Slater and Savelski, 2009). The open literature does not contain much
work on comparing different pharmaceutical products based on their environmental
impacts, and specifically, no study is there on comparing paracetamol dosage forms. In
this context, the present study carries out an environmental impacts assessment of par-
acetamol tablet and paracetamol syrup to compare their environmental friendliness. This
is done using the LCA technique. The life cycle assessment approach takes into account
many logistical activities like packaging and distribution plus the standard product design
and manufacturing processes (Zanjirani et al., 2009). The use of LCA to evaluate the sus-
tainability of manufacturing processes and products can be found in the literature (Durgesh
et al., 2011; Nigri et al., 2014; Raymond, 2013; Sharma et al., 2018). LCA technique
includes all the environmental impacts arising out of a product through its life cycle from
extraction of raw materials, production, use phase till disposal (Kumar et al., 2020). It con-
sists of four major steps; goal and scope definition, life cycle inventory analysis, life cycle
impact assessment, and interpretation (Sousa et al., 2020). LCA renders an opportunity to
mitigate environmental impacts overall manufacturing sectors (Çankaya, 2019), and some
endeavors have already been carried out to apply it in the pharmaceutical industry (Ray-
mond, 2013). LCA can be used by pharmaceutical companies to gain detailed insights into
various types of environmental impacts (Procurement of pharmaceuticals in an environ-
mental context and its inclusion into the CSR Compass, 2013). A life cycle assessment is
performed for the dosage forms to find their environmental impacts in midpoint and end-
point impact assessment categories. The results are presented in thirteen midpoint impact
categories and eleven endpoint impact categories and compared.
The study emphasizes the use of LCA in evaluating the environmental sustainability of
manufacturing processes. This study adds value to the existing knowledge by presenting
a combined conceptual and empirical approach to compare two products based on their
environmental impacts. The life cycle assessment technique is a widely used and accepted
technique, and this aspect greatly enhances the generalizability and utility of the present
study in different industrial settings. Data generated should aid the environmental man-
agers in their sustainability-related documentations. The study is more accurate over the
normal observation of a shop floor worker in the sense that it lays down a structured way
to undertake the comparison of environmental impacts of two products and takes a holistic

13
12448 R. K. Sharma et al.

view while performing environmental sustainability assessment. A major advantage of the

approach is that it helps in finding the environmental impact hotspots, based on which sub-
sequent reduced environmental footprint of the supply network can be achieved by adop-
tion of the state of art technologies, new raw materials leading to improved quality as well
as environment friendliness of the products. Supply chain mapping, data collection, and
analysis related to energy and resources consumption of the product are other benefits of
the approach.
The research paper is structured as follows. We begin with an introduction in Sect. 1,
followed by a literature review in Sect. 2. This is followed by Sect. 3 that presents the mate-
rial and methods. Section 4 presents results and discussion, followed by sensitivity analy-
sis in Sect. 5. Conclusions are presented in Sect. 6. Finally, Sect. 7 presents the research
implications.

2 Literature review

Pharmaceuticals are substances that are intended to be used for diagnosis, curing, miti-
gation, prevention, and treatment of diseases. The global pharmaceutical market is esti-
mated to be worth $844,676 million (The Pharmaceutical Industry in Figures, 2017). The
pharmaceutical industry accounted for 3.8% of gross value added (GVA) in the manufac-
turing worldwide in the year 2014 and was employing an approximate 5.1 million peo-
ple worldwide (The Pharmaceutical Industry and Global Health, 2017). There has been an
exponential growth in the pharmaceutical industry in recent decades owing to meeting the
healthcare needs of burgeoning populations. Paracetamol is among the most widely used
and popular analgesic and antipyretics (Zaid et al., 2013). Paracetamol is a common over-
the-counter drug which is extensively sold (Chiam et al., 2015). Paracetamol is used for the
relief from pain and fever (Qureshi et al., 2016).
Oral dosage forms of drugs which include tablets, oral suspensions, and capsules are
the most common methods of drug administration (Qureshi et al. 2016). The present
study compares tablet and oral suspensions (syrup) of paracetamol for their environmental
impact. The comparison assumes significance in the sense that both the dosage forms serve
the same function; however, they are produced in different ways, generating different envi-
ronmental impacts. This justifies the need of a study comparing the environmental impacts
of two dosage forms.
In the purpose of greening their supply networks, the manufacturing organizations
require to find the environmental impact of their product’s supply network. Many authors
in the past years have used different frameworks to accomplish environmental sustaina-
bility assessments. Table 1 lists major techniques used in the sustainability assessment of
manufacturing organizations in the literature. From Table 1 it could be argued that LCA is
by far the most popular tool for environmental sustainability assessment in manufacturing
organizations. The table shows that it can be used alone and also as a hybrid technique like
LCA + Integrated waste management (IWM). The fact that input data is a weak link with
all of the other assessment mechanisms while LCA has developed data sets in a number
of areas (Ness et al., 2007) is the reason for an extensive use of LCA in manufacturing
organizations. LCA is the most entrenched and well-established tool in the product-related
assessment category of tools for sustainability assessment (Ness et al., 2007). Most impor-
tantly, LCA tools have a comparatively established set of guidelines for practitioners. In

13
 Table 1  Sustainability assessment tools for manufacturing organizations used in literature
Authors
Tridech and Cheng (2010)
Liu and Srai (2011)
Ball et al. (2009)
Mayyas et al. (2012)
Yee et al. (2009)
Vinodh et al. (2016)
Iritani et al. (2015)
Reza et al. (2014)
Ren et al. (2015)
13
Purpose Framework Methodology
To understand the energy, resource efficiency, Energy, resource efficiency, and effectiveness Modeling
and effectiveness in manufacturing so as to (EREE) framework
reduce consumption of energy, waste and
carbon footprint
To propose a comprehensive approach utilizing Hotspot Quantitative and qualitative
hotspot analysis to construct added environ-
mentally sustainable supply chain
To develop a material, energy, and waste flow Material, energy, and waste (MEW) modeling Qualitative research
model toward achieving a zero-carbon manu-
facturing facility
To develop design technique for performance Life cycle assessment (LCA) Qualitative and quantitative
assessment of vehicular Body-in-White (BIW)
through its whole life cycle
To investigate the greenness and sustainability of LCA Qualitative and quantitative
palm biodiesel
To visualize and assess the performance of a LCA + value stream mapping (VSM) Quantitative
Comparing the environmental impacts of paracetamol dosage…
manufacturing process from the viewpoint of
sustainability
To evaluate the sustainability strategies by LCA Quantitative and qualitative
assessing the sustainability performance of a
wardrobe made from medium density particle
(MDP) board
To analyze the sustainability of two particular Emergy-based LCA Modeling
scenarios of a road-building project
To find the utmost sustainable scenario for Life cycle sustainability assessment framework Qualitative and quantitative research
bioethanol manufacture in China (LCSA) + multi-criteria decision making
(MCDM)
12449
 Table 1  (continued)
Authors
13
Paraskevas et al. (2015)
Egilmez et al. (2014)
Goulart Coelho and Lange (2018) For investigating sustainable solid-waste man-
Boggia et al. (2010)
Norgate and Haque (2012)
Ofori-Boateng and Lee (2014)
12450
Purpose Framework Methodology
To develop a sustainability assessment tool LCA Quantitative
for determining the most environmentally
optimal metal inputs for the recycling process
of aluminum with respect to specifications of
destination alloy
Supply chain sustainability assessment of thirty- Economic input–output (EIO) + LCA Qualitative and quantitative research
three food manufacturing sectors in the USA
LCA + Integrated waste management (IWM) Qualitative and quantitative
agement solutions in Rio de Janeiro, Brazil
Comparative assessment of production systems LCA Quantitative
of organic and organic-plus poultry
Sustainability assessment of gold production LCA Quantitative
Environmental sustainability assessment of an Exergetic LCA Mathematical modeling
oil palm-based biorefinery concept
R. K. Sharma et al.
Comparing the environmental impacts of paracetamol dosage… 12451

this sense, Table 2 summarizes a recent review of literature on LCA studies in the pharma-
ceutical sector.
(Ott et al. 2014) used the LCA methodology in quantification and assessment of poten-
tial environmental impacts related to the production of an active pharmaceutical ingredi-
ents (API) production process. An API is any substance utilized in the manufacture a drug
product and is an active ingredient in the drug product. Table 2 details the previous LCA
studies reflecting on the purpose for which they were conducted and the significant find-
ings of these studies. The main purpose of summarizing these studies is to find out if there
are any existing studies conducted on comparison of paracetamol dosage forms and to
understand how LCA has been used to carry environmental sustainability assessment and
improvement in manufacturing organizations.
A literature search indicates that though there are a good number of studies evaluating
sustainability using LCA in pharmaceutical industries, but not much work is presented on
comparison of different pharmaceutical products and more precisely, no work is presented
on comparison of paracetamol dosage forms on the basis of their environmental impacts.
It is important to highlight that most of the work is focused on the upstream part of the
pharmaceutical supply chain that is API production. Since the consumption of paracetamol
is on a large scale [Global Acetaminophen (Paracetamol) Market Set for Rapid Growth, To
Reach Around USD 999.4 Million by 2020, 2016], working on improving its sustainability
will reap good environmental benefits. An LCA study on paracetamol dosage forms will
support in enhancing the sphere of knowledge of the life cycle performance of paracetamol
production. So to contribute to the existing LCA studies in the pharmaceutical sector, the
goal of this study is to perform a LCA study of two different dosage forms of paracetamol.

3 Materials and methods

The LCA method has been utilized to perform a sustainability assessment of the two dos-
age forms of paracetamol. LCA is a widely utilized tool in sustainability assessment. LCA
approach renders an opportunity to mitigate environmental impacts in manufacturing pro-
cesses. LCA helps in the quantification of impacts at process level (Nygren & Riina, 2010).
The study takes place in two main steps. First is the collection of field data, and second is
the application of LCA technique to calculate the environmental impacts.

Step 1 Collection of field data—The field data were collected using real-time data col-
lection and technical documents like batch manufacturing records (BMR’s) utilized by
the pharmaceutical manufacturing organization. The company is located in the northern
part of India and is involved in manufacturing pharmaceutical formulations. Company
representatives were also interviewed for better clarity and understanding of the manu-
facturing process. Table 3 lists the techniques for field data collection.
Step 2 Life cycle assessment of the paracetamol dosage forms—Consequent to data col-
lection, the next step is to perform the life cycle assessment. The life cycle assessment
of the production of the dosage forms was done in accordance with the ISO 140040
standards for life cycle assessment. The main steps performed during life cycle analysis
include the goal and scope definition, life cycle inventory, and life cycle impact assess-
ment. Life cycle assessment steps are explained in detail in following Sect. 3.1.

13
 Table 2  Recent LCA studies in pharmaceutical sector
Authors
13
Wernet et al. (2010)
Jiménez-González and Overcash (2014) Focus on identifying the problems faced to produce the inven-
Jiménez-González et al. (2004)
Ott et al. (2014)
Carole et al. (2008)
Raymond et al. (2010)
Amelio et al. (2014)
Raju et al. (2016)
Belboom et al. (2011)
Dhaliwal et al. (2014)
Cespi et al. (2015)
Kim et al. (2009)
Purpose of the study
Environmental impacts of active pharmaceutical ingredients
(API) production
tory data for life cycle analysis and using the LCA results for
decision making
Identified and analyzed the environmental impacts in the synthe- Solvent use accounted for most impacts related to the manufac-
sis of a typical API
Presented life cycle-based process optimization of an existing
API production process
Evaluated various solvent recovery options in API production
Analysis of solvent waste issues in pharmaceutical production
Utilization LCA for evaluating two treatment alternatives for
waste solvents in API production
Compared environmental impacts of two different types of
packaging of paracetamol tablets
Comparison of two primary packaging options for injectable
drugs
LCA of packaging alternatives for delivery of contrast media
packaging
Life cycle inventory (LCI) improvement in the pharmaceutical
sector by presenting a LCA of a pharmaceutical product
LCA of three immobilized enzymes to be used in pharmaceuti- Immobilization and subprocesses for media preparation contrib-
cal products
12452
Major findings/environmental hotspots identified
Resource consumption and emissions arising out of energy
production
More demand for life cycle information in the form of product
category rules, environmental product declarations, will lead to
enhanced life cycle inventory data creation
ture of pharmaceutical product studied
Supply of key input material, solvent, and catalyst were identified
as key improvement areas.
Yield enhancement, recycling of solvent, and catalyst fixation/
change were the suggested ecological improvements.
Treatment of the waste by combined pervaporation–distilla-
tion and conventional methods was found as the better solvent
recovery option based on LCA
Solvent manufacture and incineration are the major impact con-
tributors to life cycle emissions
Production of solvents has a major impact and should be consid-
ered while selecting incineration or distillation method.
Production of aluminum foils is major contributor to the environ-
mental aluminum blister packaging
Water heating to clean components of glass vial is the major
energy use hotspot. Production of polymer vials causes a major
environment impact.
The polymer bottle performs better than comparably sized glass
bottles in terms of environmental impacts owing to lower mass,
lesser impacts due to distribution and lesser end-of-life disposal
impacts
A practical approach for building inventories utilizing data from
literature and patents
R. K. Sharma et al.
ute to maximum environmental impact
 Table 2  (continued)
Authors
Mata et al. (2012)
Siegert et al. (2020)
Jeswani and Azapagic (2019)
Renteria Gamiz et al. (2019)
Parvatker et al. (2019)
(Vozzola et al. (2018)
Savelski et al. (2017)
Lee et al. (2016)
Rodríguez et al. (2016)
Iolanda De Marco et al. (2016)
Zerazion et al. (2016)
Pérez-López et al. (2016)
13
Purpose of the study
To develop a tool for life cycle assessment
Cradle-to-grave LCA of ibuprofen analgesic
Estimation of the environmental footprints of inhaler devices
employed to deliver inhalation medicines
Environmental sustainability assessment of the production
process of a biological API
Cradle-to-gate greenhouse gas emissions for 20 anesthetic API’s Greenhouse gas emissions are positively correlated to the number
LCA of reusable and disposable cleanroom coveralls
Design alternatives exploration for the purification and potential LCA results reveal a reduction in the environmental impacts
reusage of organic solvents waste streams during manufactur-
ing of pharmaceuticals
LCA-based comparison of the environmental performance of
batch and continuous processing in pharmaceutical industry
LCA-based comparison and evaluation of two different waste
water treatment processes in a pharmaceutical industry
To perform LCA of starch aerogels utilized for biomedical
applications
Environmental impact assessment of curcumin synthesis and
extraction
Assessment of the environmental impacts related to production Two optimized scenarios were presented based on the LCA
of five essential terpene oils using LCA technique
Major findings/environmental hotspots identified
An excel-based LCA tool to evaluate the sustainability of phar-
maceutical products
The production stage dominates the environmental profile, while
the use and end-of-life are minor contributors to the overall
results
HFC-152a inhaler has lower impact in majority of impact catego-
ries considered as compared to dry powder inhaler
Main driving factors in the environmental impact of manufactur-
ing of biologically active pharmaceutical ingredient are culture
media nutrients and cleanroom requirements
of synthesis steps in drug manufacturing
Among all the environmental parameters considered the reusable
coveralls considerably outperformed the disposable coveralls
when solvent recovery methods are applied
Comparing the environmental impacts of paracetamol dosage…
Using continuous processing is more environmental friendly
for 4-DEL production compared to batch production owing to
lesser plant footprint and lesser cleaning of the equipment’s
Heterogeneous Fenton process is found to be more environmental
friendly compared to homogenous Fenton process
Environmental impacts arising out of the production can be
reduced by considering improved solutions
The procedure of obtaining highly pure curcumin from the chemi-
cal synthesis of curcumin, causes less environmental impact
results leading to improvements in the environmental profile of
system
12453
 Table 2  (continued)
12454

Authors Purpose of the study Major findings/environmental hotspots identified

13
Cespi et al. (2015) LCA of biorefinery products based on varied allocation proce- The outcome provides a range of LCA metrics highlighting at
dures the contrasts in results according to the allocation procedure
followed
Sharma and Hussain (2020) Discussion on smart nanomaterials and elaborate utilization in The study comprehends organized process for commercial use of
pharma analysis smart nanomaterials in the pharma analysis
R. K. Sharma et al.
Comparing the environmental impacts of paracetamol dosage… 12455

Table 3  Techniques for field data collection

Method of data collection Source of data

Analysis of internal technical documents of the
company
Interviews and discussion with company personnel/
real-time data collection
Process flowchart to map the production system of
the dosage forms
Packing records for data related to consumption of
packing material.
Batch manufacturing records to understand the
chemical composition of the selected dosage form
and step-by-step addition of ingredients during each
process.
Details of manufacturing equipment (name, capacity,
quantity, etc.)
List of utilities (Compressors, boilers, etc.)
Field data were collected through company visits and
to understand the production process.
Company representatives were interviewed for better
clarity on the production processes.

3.1 Life cycle assessment

Life cycle assessment is a thorough analytical method for quantifying environmental

impacts and has been mainly focused on products (Jacquemin et al., 2012). US Environ-
mental protection agency in 2006 published “Life Cycle Assessment: Principles and Prac-
tice” which gives an elaborate guideline on how to carry an LCA analysis (Williams, 2009).
LCA analyses give a number of useful results that aid decision makers in industry, service
sector, government, and non-governmental organizations (Rybaczewska-Blażejowska and
Palekhov, 2018). Commercial LCA software packages like GaBi are available to carry out
the life cycle assessment of processes and products. The present study uses GaBi™ v8.0
(GaBi Software, 2020) life cycle assessment software for life cycle impact assessment and
life cycle inventory compilation. The steps involved in the life cycle assessment compari-
son of paracetamol tablet and syrup are explained in the following paragraphs.

3.1.1 Goal and scope definition

The goal of this study is to evaluate and compare the environmental impacts of two differ-
ent dosage forms of paracetamol, tablet and syrup. The system boundary is a function of
the goal of the study (Tillman et al., 1994). Keeping with the goal of the study, the objec-
tive of the present research is the ‘cradle to gate’ assessment of the production of paraceta-
mol dosage forms. As a result, this study provides an environmental footprint at various
levels of the pharmaceutical supply network, thus strengthening the propensity to identify
the nodes of environmental impacts across the supply chain.

3.1.2 Functional unit

The functional unit is linked to the goal and scope of the study. Since the focus of the
present study was a comparison of production of a particular batch of paracetamol
dosage forms, the functional unit was taken as one batch (One batch of tablet = One

13
12456 R. K. Sharma et al.

hundred thousand, 500 mg tablets; and One batch of syrup = Ten thousand bottles each
containing 100 ml syrup) of paracetamol dosage forms. Both require the same amount
of API for production.

3.1.3 Allocation aspects

Allocation refers to dividing the environmental impacts among various products and/or
among successive product systems (Jungmeier et al., 2002). The production of paraceta-
mol tablets and paracetamol syrup is a very concentrated process, and no by-products of
value are produced by the production process. Therefore, we were able to prevent any
allocation problems in the present research. The LCA system boundary for paracetamol
tablet production has been taken from (Sharma et al., 2020). The LCA system boundary
for paracetamol syrup production is presented in Fig. 1.
Life Cycle Inventory: The life cycle inventory data were obtained from primary and
secondary sources. The data collected from the primary and secondary data sources are
merged to do the life cycle inventory analysis. The secondary data are from the GaBi
v8.0 life cycle assessment software database (GaBi Software, 2020). The specifications
of the major equipment used in the manufacturing processes of paracetamol tablets are
given in Table 4. Paracetamol syrup production process key points: The syrup produc-
tion process as presented in Fig. 1 consists of two major constituent processes—‘syrup
preparation’ and ‘packaging.’ There is an intermediate ‘storage’ process between the
two processes. There are two utility processes—‘steam production’ and ‘deionized
water production.’ The steam and the deionized water produced are used in both the
major processes (Liquid production and packaging).
The life cycle inventory data for the paracetamol tablet production are taken from
(Sharma et al., 2020). The life cycle inventory data for paracetamol syrup are given in
Table 5.

Raw Deionized water

material production Finished
product
Energy
Waste
Water Indian
electricity mix Pollution
Steam
production

Liquid Packing
preparation

Packaging
material

Fig. 1  The LCA system boundaries for paracetamol syrup production

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Comparing the environmental impacts of paracetamol dosage… 12457

Table 4  Specifications of the major equipment used in the manufacturing processes of paracetamol tablet
Equipment Vibro-sifter Paste kettle Rapid Fluid bed Sifter cum Cage Com-
→ mixer dryer multi-mill blender pression
granulator machine

Power rating 0.370 2.250 27.000 13.500 4.125 6.750 3.750

(kW)
Time/batch* 0.50 0.25 0.13 0.17 0.58 0.25 5.69
(hr.)
Power con- 0.185 0.563 3.600 2.250 2.406 1.688 21.338
sumption
per batch
(kWh)

Table 5  Life cycle inventory data paracetamol syrup production

Resources Unit Liquid production Packing Demineralized water Steam

Aspartic acid, methyl ester kg 0.50 – – –

Bronopol kg 0.80 – – –
Citric acid kg 1.00 – – –
Erythrosine kg 0.06 – – –
Fumed Silica kg 2.00 – – –
Paracetamol API kg 50.00 – – –
Ethyl butyrate kg 1.76 – – –
Propyl Paraben Sodium kg 0.25 – –
Sodium citrate kg 1.00 – – –
Sodium Methyl Paraben kg 1.00 – – –
Sorbitol kg 60.00 – – –
Sugar kg 600 – – –
Xanthan kg 3.00 – – –
100 ML Round amber pet bottles Nos. – 10000.00 – –
Cap Nos. – 10000.00 – –
Label Nos. – 10000.00 – –
Chlorine kg – – 1.71E–02 1.19E–03
Sodium chloride kg – – 5.14E+00 3.58E–01
Sodium hexametaphosphate kg – – 1.37E–02 9.52E–04
Sodium hypochlorite kg – – 1.71E–02 1.19E–03
Sodium pyrosulfite kg – – 1.37E–02 9.52E–04
Calcium carbonate kg – – – 5.38E–01
Diesel kg – – – 3.35E+01
Alum kg – – – –
Carbamide (urea) kg – – – –
Diammonium phosphate kg – – – –
Polyacrylamide kg – – – –
Water (ground water) kg – – 3.21E+03 2.67E+02
Demineralized Water kg 1000.00 800.00 – –
Steam kg 220.00 – – –
Electrical energy kWh 21.00 10.50 3.10E+01 5.71E+00

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12458 R. K. Sharma et al.

3.2 Life cycle impact assessment (LCIA)

Impact assessment aids in making the right conclusions (Saur et al., 1996). Midpoint and
endpoint impact assessment methods from ‘ReCiPe’ impact assessment method (ReCiPe
method for the impact assessment, 2011) are used to carry out the life cycle impact assess-
ment. The endpoint approach assesses at the ecosystem, resources, and human health
level, which are area of protection (AOP) level while the midpoint approach assesses the
environmental effects at a particular position in the cause–effect chain starting from the
substance emission till the endpoint level (Dong and Ng, 2014). ReCiPe method is used
because it contains the broadest collection of midpoint impact categories (ReCiPe|PRé
Sustainability, 2019). The midpoint assessment results are assessed in thirteen impact cat-
egories which are; climate change, incl. biogenic carbon (CC), fine particulate matter for-
mation (FPMF), fossil depletion (FD), freshwater consumption (FC), freshwater ecotoxic-
ity (FET), freshwater eutrophication (FE), human toxicity, cancer (HT), ionizing radiation
(IR), land use (LU), metal depletion (MD), photochemical ozone formation, human health
(POF), stratospheric ozone depletion (SOD), and terrestrial ecotoxicity (TE) categories
using the ReCiPe method. The endpoint assessment results for the study are assessed in
the eleven impact categories—climate change human health (CC), fine particulate matter
formation (FPMF), freshwater consumption (FC), freshwater ecotoxicity (FET), freshwater
eutrophication (FE), human toxicity, cancer (HT), ionizing radiation (IR), land use (LU),
photochemical ozone formation (POF), stratospheric ozone depletion (SOD), and terres-
trial ecotoxicity (TE). The unit ‘DALY’ stands for disability-adjusted life years and repre-
sents the lost years or a person is disabled as a cause of an accident or a disease (Huijbregts
et al., 2016). The unit for the quality of the ecosystem ‘species.yr’ is the loss in local spe-
cies when integrated over time (Huijbregts et al., 2016).

4 Results and discussion

This section discusses in detail the environmental impacts of the dosage forms production.
Life cycle impact assessment can be performed utilizing endpoint and midpoint impact
approaches. In the present study the results are presented in thirteen midpoint and eleven
endpoint impact categories to make a holistic comparison of the environmental impacts.
The results have been analyzed to identify the cause of the high impact by identifying
the high impact generating constituent processes. The following subsections present the
obtained results.

4.1 Results in midpoint impact categories

The midpoint assessment results are presented in Fig. 2. Syrup production has more than
80% contribution in CC impact category. Syrup production has more than 50% environ-
mental impact in FPMF, FD, FC, FET, FE, IR, POF, SOD, and TE categories.
The syrup production has majority impacts in CC, FD, FC and FE impact categories.
The impacts in these categories can be related to their origin. The results in the FC
impact category are related to freshwater consumption. The syrup production process
has more impacts in this category owing to high freshwater consumption relative to the
tablet production process. Impacts in FD impact category arise out of the production of

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Comparing the environmental impacts of paracetamol dosage… 12459

Syrup Tablet

Terrestrial eco toxicity, kg 1,4 - DB eq. 167 29.29

Stratospheric Ozone Depletion, kg CFC - 11 eq. 3.71E-05 0.000007

Photochemical Ozone Formation, Human Health, kg NOx eq. 130 29.13

Metal depletion, kg Cu eq. 0.0419 0.33

Land use, Annual crop eq. y 1.29 1.19

Ionizing Radiation, Bq C - 60 eq. to air 1.59 0.63

Human toxicity, cancer, kg 1,4 - DB eq. 2.55 2.66

Freshwater Eutrophication, kg P eq. 0.003 0.000067

Freshwater eco toxicity, kg 1,4 DB eq. 0.0369 0.006

Freshwater Consumption, m3 12.1 0.31

Fossil depletion, kg oil eq. 335 15.86

Fine Particulate Matter Formation, kg PM2.5 eq. 0.891 0.085

Climate change, incl biogenic carbon, kg CO2 eq. 524 33.21

Fig. 2  Midpoint impact assessment of paracetamol dosage forms

the packing material, PET bottles and caps for the syrup and polyvinyl chloride sheets
for tablets. These packing materials are derived from fossil fuels. Impacts in the FD
impact category can also be attributed to the use of diesel to run the steam genera-
tion equipment. Packaging material production also contributes to impacts in CC impact
category. Alfarisi and Primadasa (2018) state that PET bottle production (which is a
packaging material for syrup) contributes significantly to climate change potential.
POF impacts occur during the processing of fossil fuel (Comanita et al., 2015), that is
‘diesel’ in this process. Tablet production has considerable impacts in HT, IR, and MD
impact categories. The major impact in the HT impact category arises out of the blis-
ter packaging process, further in which the polyvinyl chloride (PVC) sheet production
causes a major impact. Comanita et al. (2015) state that PVC production has impacts on
the environment with a high contribution to human toxicity (HT) potential.

Syrup Tablet

Terrestrial eco toxicity [species.yr] 1.91E-09 3.34E-10

Stratospheric Ozone Depletion [DALY] 4.97E-08 1.03E-08

Photochemical Ozone Formation, Human Health [DALY] 0.000119 2.65E-05

Land use [species.yr] 1.15E-08 1.06E-08

Ionizing Radiation [DALY] 2.22E-08 8.86E-09

Human toxicity, cancer [DALY] 8.47E-06 8.87E-06

Freshwater Eutrophication [species.yr] 2.01E-09 4.42E-11

Freshwater eco toxicity [species.yr] 2.56E-11 4.72E-12

Freshwater Consumption, Human Health [DALY] 1.76E-05 3.38E-07

Fine Particulate Matter Formation [DALY] 0.00056 5.40E-05

Climate Change Human Health, incl biogenic carbon 0.00654 0.00041528
[DALY]

Fig. 3  Endpoint assessment of paracetamol dosage forms

13
12460 R. K. Sharma et al.

4.2 Results in endpoint impact categories

The endpoint environmental impact assessment results are in shown in Fig. 3. In the end-
point impact assessment, syrup production contributes more than 90% of the total impacts
in CC impact category. Syrup production causes major impacts (more than 70%) in 8 out
of the 11 categories under consideration (as shown in Fig. 3). It is observed that similar to
the midpoint impact categories, syrup production has shown the maximum impact in CC,
FPMF, FC, FET, FE, IR, POF, SOD, and TE impact categories. Tablet production has con-
siderable impacts in HT and LU impact categories.
The results present the environmental impacts of two paracetamol dosage forms in
thirteen midpoint and eleven endpoint impact categories. These results help us to make
a detailed comparison of the two dosage forms in terms of their environmental impacts.
The dominant dosage form in each impact category can be identified from the results as
is visible in Figs. 2 and 3. The constituent processes (example—blister packaging in case
of paracetamol tablet) that are major contributors to environmental impacts in an impact
category are identified and presented here. This identification of the constituent hotspot
processes allows that the environmental managers can look for green practices/interven-
tions like better raw materials, improved technologies, and efficient environmental man-
agement techniques to improve the environmental profile of their production processes.
The results are able to demonstrate an approach to compare the environmental footprint
of the dosage forms of paracetamol and to improve their environmental performance. The
approach can also be replicated in other manufacturing organizations. Data collection and
analysis related to energy and resources consumption takes place while carrying out the
LCA; this will help in sustainability-related documentation of the companies. The advan-
tages of the approach include finding the environmental impact hotspot processes and the
application of green interventions. The said approach is based on the LCA technique which
is a very robust and popular technique. The developed approach expands the scope of the
analyses that could be done using LCA technique, as the environmental impact hotspots
are identified at different levels of the supply network of a product. This approach is more
accurate than the normal observation of a shop floor worker in the sense that it lays down
a structured way to undertake the sustainability implementation and takes a holistic view
while evaluating the consumption of resources in a process and environmental sustainabil-
ity assessment. Limitations include that the results present an Indian perspective. The una-
vailability of inventory data for some reagents and chemicals is another limitation of the
study. The results are limited by the boundary conditions specified, certain processes are
excluded, which may be included in future studies.

5 Sensitivity analysis

Sensitivity analysis is an uncomplicated technique to assess the ruggedness and robustness

of the results that are obtained from the impact assessment (Singh and Sarkar, 2019). The
technique employs the method of varying the values of an independent input variable and
then measuring its effect on the dependent variable (Prakash and Barua, 2015). Examples
of using sensitivity analysis to evaluate the result robustness can be found in various stud-
ies. Niero et al. (2014) used sensitivity analysis to enhance the robustness of their find-
ings. Welz et al. (2011) performed a sensitivity analysis by varying the electricity mix and

13
Comparing the environmental impacts of paracetamol dosage… 12461

methods of impact assessment. The current study follows it by varying the Indian electric-
ity mix with the US electricity mix for carrying out the sensitivity analysis. Since there is
a significant use of electricity mixes in all the constituent processes therefore a sensitivity
analysis based on varying two different electricity mixes will help in improving the robust-
ness and transparency of the results. Sensitivity analysis for the LCA analysis process by
varying electricity mix for paracetamol syrup is given in Fig. 4. It can be concluded from
the sensitivity analysis results that impact assessment has provided the robust results.

6 Conclusions

The present study aimed to compare the environmental impacts of two paracetamol dosage
forms using life cycle assessment. The study aimed to emphasize the use of LCA in eval-
uating the environmental sustainability of manufacturing processes. The results obtained
from the assessment have been able to identify the environmental impacts related to the
production of each of the dosage forms. The obtained impact assessment results have been
used to make a comparison of the two dosage forms on the basis of their environmental
impacts in midpoint and endpoint impact assessment categories. Midpoint impact assess-
ment results show that syrup production has 90% contribution in climate change impact
category. Syrup production has more than 50% environmental impact in fine particulate
matter formation, fossil depletion, freshwater consumption, freshwater eutrophication,
freshwater ecotoxicity, ionizing radiation, photochemical ozone formation, stratospheric
ozone depletion, and terrestrial ecotoxicity midpoint impact categories. Tablet produc-
tion has major impacts in human toxicity, ionizing radiation and metal depletion midpoint
impact categories. Syrup production causes major impacts (more than 70%) in 8 out of
the 11 endpoint impact categories, while tablet production has a major impact in human
toxicity, and ionizing radiation endpoint impact categories. Packing material production is
the main contributor in CC category. PET bottle and its cap manufacturing are the major
contributing process in FD category. Diesel use in steam generation leads to impacts in
FD impact category. The study has been able to make a comparison of the environmental
impacts of two paracetamol dosage forms. Syrup production has a visibly higher impact in
more number of midpoint as well as endpoint impact categories considered. The outcome

600 535
482
500
400 331 343
300
200
100
11.8 8.06
0
US Electricity Mix Indian Electricity Mix

Climate change, incl biogenic carbon [kg CO2 eq.] Fossil depletion [kg oil eq.]

Fig. 4  Sensitivity analysis for paracetamol syrup

13
12462 R. K. Sharma et al.

of the study is an approach based on LCA technique to compare the environmental impacts
of two dosage forms along with the identification of constituent hotspot processes. The
study lays down a structured approach to assess the environmental impacts using LCA. As
a future scope, the research can be expanded by including another important aspect, that is,
consumer preferences. Ease of intake is one such aspect, which goes in favor of the syrup
dosage form; however, tablets score more in the ease of storage criterion. The preference
of dosage forms is also age-dependent with the children preferring to go for the syrup. The
shelf life of a dosage form is also an important aspect; tablets usually have longer shelf life
than liquid formulations. A detailed analysis of consumer preferences can be combined
with this study to get a high-resolution picture of the situation. Application of a multicrite-
ria method, to find which is the best process and complementing the analysis with the life
cycle analysis, is a future scope of this study. Technological interventions can be evaluated
on their improvement potential and then can be applied to the hotspots to mitigate their
environmental impacts. Sustainability managers will find a practical approach in this study,
to find the environmental hotspots in the supply networks of the products manufactured in
their organizations.

Acknowledgements The authors wish to acknowledge the DST funding for this work through the DST-
EPSRC grant on project, Engineering driven sustainable supply network design.

References
Alfarisi, S., & Primadasa, R. (2018). Carbon footprint and life cycle assessment of PET bottle manufactur-
ing process. In: Proceedings of the the 1st international conference on computer science and engineer-
ing technology Universitas Muria Kudus [Internet]. Kudus, Indonesia: EAI. https://​doi.​org/​10.​4108/​
eai.​24-​10-​2018.​22805​96.
Amelio, A., Genduso, G., Vreysen, S., Luis, P., & Van der Bruggen, B. (2014). Guidelines based on life
cycle assessment for solvent selection during the process design and evaluation of treatment alterna-
tives. Green Chemistry, 16(6), 3045–3063. https://​doi.​org/​10.​1039/​C3GC4​2513D.
Ball, P. D., Evans, S., Levers, A., & Ellison, D. (2009). Zero carbon manufacturing facility—towards inte-
grating material, energy, and waste process flows. Proceedings of the Institution of Mechanical Engi-
neers, Part B: Journal of Engineering Manufacture., 223(9), 1085–1096. https://​doi.​org/​10.​1243/​
09544​054JE​M1357.
Belboom, S., Renzoni, R., Verjans, B., Léonard, A., & Germain, A. (2011). A life cycle assessment of
injectable drug primary packaging: comparing the traditional process in glass vials with the closed
vial technology (polymer vials). The International Journal of Life Cycle Assessment, 16(2), 159–167.
https://​doi.​org/​10.​1007/​s11367-​011-​0248-z.
Boggia, A., Paolotti, L., & Castellini, C. (2010). Environmental impact evaluation of conventional, organic
and organic-plus poultry production systems using life cycle assessment. World’s Poultry Science
Journal, 66(1), 95–114. https://​doi.​org/​10.​1017/​S0043​93391​00001​03.
Çankaya, S. (2019). Investigating the environmental impacts of alternative fuel usage in cement production:
A life cycle approach. Environment, Development and Sustainability, 22, 7495–7514.
Carole, W. A., Slater, C. S. C., Savelski, M. J., Moroz, T. M., Furiato, A., & Rowan, K. L. (2008). Use of
life cycle assessment in evaluating solvent recovery alternatives in pharmaceutical manufacture. In: 8th
International conference on ecobalance. Tokyo, Japan.
Cespi, D., Beach, E. S., Swarr, T. E., Passarini, F., Vassura, I., Dunn, P. J., & Anastas, P. T. (2015). Life
cycle inventory improvement in the pharmaceutical sector: Assessment of the sustainability combining
PMI and LCA tools. Green Chemistry, 17(6), 3390–3400. https://​doi.​org/​10.​1039/​C5GC0​0424A.
Chiam, E., Weinberg, L., & Bellomo, R. (2015). Paracetamol: A review with specific focus on the haemody-
namic effects of intravenous administration. Heart, Lung and Vessels, 7(2), 121–132.
Comanita, E. D., Ghinea, C., Rosca, M., Simion, I. M., Petraru, M., & Gavrilescu, M. (2015). Environmen-
tal impacts of polyvinyl chloride (PVC) production process. In: 2015 E-Health and Bioengineering
Conference (EHB) [Internet]. Iasi, Romania: IEEE; [accessed 2019 Nov 6]; p. 1–4. https://​doi.​org/​10.​
1109/​EHB.​2015.​73914​86.

13
Comparing the environmental impacts of paracetamol dosage… 12463

Dhaliwal, H., Browne, M., Flanagan, W., Laurin, L., & Hamilton, M. (2014). A life cycle assessment
of packaging options for contrast media delivery: Comparing polymer bottle versus glass bottle.
The International Journal of Life Cycle Assessment, 19(12), 1965–1973. https://​doi.​org/​10.​1007/​
s11367-​014-​0795-1.
Dong, Y. H., & Ng, S. T. (2014). Comparing the midpoint and endpoint approaches based on ReCiPe—a
study of commercial buildings in Hong Kong. The International Journal of Life Cycle Assessment,
19(7), 1409–1423. https://​doi.​org/​10.​1007/​s11367-​014-​0743-0.
Durgesh, J., Modi, Y., & Ravi, B. (2011). Evaluating environmental impacts of sand cast products using life
cycle assessment. Research into Design—Supporting Sustainable Product Development (pp. 551–558).
Bangalore, India: Research Publishing.
Egilmez, G., Kucukvar, M., Tatari, O., & Bhutta, M. K. S. (2014). Supply chain sustainability assessment
of the U.S. food manufacturing sectors: A life cycle-based frontier approach. Resources, Conservation
and Recycling, 82, 8–20. https://​doi.​org/​10.​1016/j.​resco​nrec.​2013.​10.​008.
GaBi, S. (2020). [accessed 2020 Jul 22]. http://​www.​gabi-​softw​are.​com/​inter​natio​nal/​softw​are/​gabi-​softw​
are/.
Global Acetaminophen (Paracetamol) Market set for rapid growth, to reach around USD 999.4 Mil-
lion by 2020 (2016). https://​www.​marke​trese​archs​tore.​com/​news/​global-​aceta​minop​hen-​parac​
etamol-​market-​148.
Goulart Coelho, L. M., & Lange, L. C. (2018). Applying life cycle assessment to support environmentally
sustainable waste management strategies in Brazil. Resources, Conservation and Recycling, 128, 438–
450. https://​doi.​org/​10.​1016/j.​resco​nrec.​2016.​09.​026.
Huijbregts, M. A. J., Steinmann, Z. J. N., Elshout, P. M. F., Stam, G., Verones, F., Vieira, M. D. M., et al.
(2016). ReCiPe 2016 A harmonized life cycle impact assessment method at midpoint and endpoint
level Report I: Characterization. International Journal of Life Cycle Assessment, 22, 138–147.
Iolanda, M. D., Miranda, S., Riemma, S., & Iannone, R. (2016). LCA of starch aerogels for biomedical
applications. Chemical Engineering Transactions, 49, 319–324. https://​doi.​org/​10.​3303/​CET16​49054.
Iritani, D. R., Silva, D. A. L., Saavedra, Y. M. B., Grael, P. F. F., & Ometto, A. R. (2015). Sustainable strate-
gies analysis through Life Cycle Assessment: A case study in a furniture industry. Journal of Cleaner
Production, 96, 308–318. https://​doi.​org/​10.​1016/j.​jclep​ro.​2014.​05.​029.
Jacquemin, L., Pontalier, P. Y., & Sablayrolles, C. (2012). Life cycle assessment (LCA) applied to the
process industry: A review. The International Journal of Life Cycle Assessment, 17(8), 1028–1041.
https://​doi.​org/​10.​1007/​s11367-​012-​0432-9.
Jeswani, H. K., & Azapagic, A. (2019). Life cycle environmental impacts of inhalers. Journal of Cleaner
Production, 237, 117733. https://​doi.​org/​10.​1016/j.​jclep​ro.​2019.​117733.
Jiménez-González, C., Curzons, A. D., Constable, D. J., & Cunningham, V. L. (2004). Cradle-to-gate life
cycle inventory and assessment of pharmaceutical compounds. The International Journal of Life Cycle
Assessment, 9(2), 114–121.
Jiménez-González, C., & Overcash, M. R. (2014). The evolution of life cycle assessment in pharmaceuti-
cal and chemical applications—a perspective. Green Chemistry, 16(7), 3392–3400. https://​doi.​org/​10.​
1039/​C4GC0​0790E.
Jungmeier, G., Werner, F., Jarnehammar, A., Hohenthal, C., & Richter, K. (2002). Allocation in LCA of
wood-based products experiences of cost action E9. The International Journal of Life Cycle Assess-
ment, 7(6), 369–375. https://​doi.​org/​10.​1007/​BF029​78686.
Kim, S., Jiménez-González, C., & Dale, B. E. (2009). Enzymes for pharmaceutical applications—a cradle-
to-gate life cycle assessment. International Journal of Life Cycle Assessment, 14(5), 392–400. https://​
doi.​org/​10.​1007/​s11367-​009-​0081-9.
Kloepffer, W. (2008). Life cycle sustainability assessment of products with: (Comments by Helias A Udo de
Haes)t. International Journal of Life Cycle Assessment, 13(2), 89–95. https://​doi.​org/​10.​1065/​lca20​08.​
02.​376.
Kumar, H., Azad, A., Gupta, A., Sharma, J., Bherwani, H., Labhsetwar, N. K., & Kumar, R. (2020).
COVID-19 Creating another problem? Sustainable solution for PPE disposal through LCA approach.
Environ Dev Sustain [Internet]. [accessed 2021 Feb 3]. https://​doi.​org/​10.​1007/​s10668-​020-​01033-0.
Lee, C. K., Khoo, H. H., & Tan, R. B. H. (2016). Life cyle assessment based environmental performance
comparison of batch and continuous processing: A case of 4-d-erythronolactone synthesis. Organic
Process Research & Development, 20(11), 1937–1948. https://​doi.​org/​10.​1021/​acs.​oprd.​6b002​75.
Linton, J., Klassen, R., & Jayaraman, V. (2007). Sustainable supply chains: An introduction. Journal of
Operations Management, 25(6), 1075–1082. https://​doi.​org/​10.​1016/j.​jom.​2007.​01.​012.
Liu, Y., & Srai, J. S. (2011). Sustainable supply chain configuration: proposing a hot spot analysis
methodology. In: Proceedings of the international conference on materials science, metal and
manufacturing. Singapore.

13
12464 R. K. Sharma et al.

Mata, M. T., Martins, A. A., Neto, B., Martins, L. M., Salcedo, L. R. R., & Costa, A. V. C. (2012). LCA
Tool for Sustainability Evaluations in the Pharmaceutical Industry. Chemical Engineering Transac-
tions, 26.
Mayyas, A. T., Qattawi, A., Mayyas, A. R., & Omar, M. A. (2012). Life cycle assessment-based selection
for a sustainable lightweight body-in-white design. Energy, 39(1), 412–425. https://​doi.​org/​10.​1016/j.​
energy.​2011.​12.​033.
Ness, B., Urbel-Piirsalu, E., Anderberg, S., & Olsson, L. (2007). Categorising tools for sustainability assess-
ment. Ecological Economics, 60(3), 498–508. https://​doi.​org/​10.​1016/j.​ecole​con.​2006.​07.​023.
Niero, M., Pizzol, M., Bruun, H. G., & Thomsen, M. (2014). Comparative life cycle assessment of waste-
water treatment in Denmark including sensitivity and uncertainty analysis. Journal of Cleaner Produc-
tion, 68, 25–35. https://​doi.​org/​10.​1016/j.​jclep​ro.​2013.​12.​051.
Nigri, E. M., de Barros, A. C., Rocha, S. D. F., & Romeiro Filho, E. (2014). Assessing environmental
impacts using a comparative LCA of industrial and artisanal production processes: “Minas Cheese”
case. Food Science and Technology (Campinas), 34(3), 522–531. https://​doi.​org/​10.​1590/​1678-​457x.​
6356.
Norgate, T., & Haque, N. (2012). Using life cycle assessment to evaluate some environmental impacts of
gold production. Journal of Cleaner Production, 29–30, 53–63. https://​doi.​org/​10.​1016/j.​jclep​ro.​2012.​
01.​042.
Nygren, J., & Riina, A. (2010). Use of life cycle assessment (LCA) in global companies [Internet]. Finland:
Finnish Environment Institute. https://​helda.​helsi​nki.​fi/​bitst​ream/​handle/​10138/​39723/​SYKEre_​16_​
2010.​pdf?​seque​nce=1.
Ofori-Boateng, C., & Lee, K. T. (2014). An oil palm-based biorefinery concept for cellulosic ethanol and
phytochemicals production: Sustainability evaluation using exergetic life cycle assessment. Applied
Thermal Engineering, 62(1), 90–104. https://​doi.​org/​10.​1016/j.​applt​herma​leng.​2013.​09.​022.
Ott, D., Kralisch, D., Denčić, I., Hessel, V., Laribi, Y., Perrichon, P. D., et al. (2014). Life cycle analysis
within pharmaceutical process optimization and intensification: Case study of active pharmaceuticalIn-
gredient production. ChemSusChem, 7(12), 3521–3533. https://​doi.​org/​10.​1002/​cssc.​20140​2313.
Paraskevas, D., Kellens, K., Dewulf, W., & Duflou, J. R. (2015). Environmental modelling of aluminium
recycling: A life cycle assessment tool for sustainable metal management. Journal of Cleaner Produc-
tion, 105, 357–370. https://​doi.​org/​10.​1016/j.​jclep​ro.​2014.​09.​102.
Parvatker, A. G., Tunceroglu, H., Sherman, J. D., Coish, P., Anastas, P., Zimmerman, J. B., & Eckelman, M.
J. (2019). Cradle-to-gate greenhouse gas emissions for twenty anesthetic active pharmaceutical ingre-
dients based on process scale-up and process design calculations. ACS Sustainable Chemistry & Engi-
neering, 7(7), 6580–6591. https://​doi.​org/​10.​1021/​acssu​schem​eng.​8b054​73.
Pérez-López, P., Jeffryes, C., Agathos, S. N., Feijoo, G., Rorrer, G., & Moreira, M. T. (2016). Environmental
life cycle optimization of essential terpene oils produced by the macroalga Ochtodes secundiramea.
Science of The Total Environment, 542, 292–305. https://​doi.​org/​10.​1016/j.​scito​tenv.​2015.​10.​045.
Prakash, C., & Barua, M. K. (2015). Integration of AHP-TOPSIS method for prioritizing the solutions of
reverse logistics adoption to overcome its barriers under fuzzy environment. Journal of Manufacturing
Systems, 37, 599–615. https://​doi.​org/​10.​1016/j.​jmsy.​2015.​03.​001
Procurement of pharmaceuticals in an environmental context and its inclusion into the CSR Compass.
(2013). Stockholm: The Swedish Environmental Protection Agency.
Qureshi, M. S., Rukh, G., Kirplani, P. D., Farheen, A., & Hamid, M. (2016). A comparative study of quality
on conventional paracetamol tablets available in Pakistan. Research in Pharmacy and Health Sciences,
2(3), 205–210. https://​doi.​org/​10.​32463/​rphs.​2016.​v02i03.​40.
Raju, G., Sarkar, P., Singla, E., Singh, H., & Sharma, R. K. (2016). Comparison of environmental sustain-
ability of pharmaceutical packaging. Perspectives in Science. https://​doi.​org/​10.​1016/j.​pisc.​2016.​06.​
058.
Raymond, M. (2013). An investigation of the potential for and application of life cycle analysis in the phar-
maceutical industry. New Jersey: Rowan University
Raymond, M. J., Slater, C. S., & Savelski, M. J. (2010). LCA approach to the analysis of solvent waste
issues in the pharmaceutical industry. Green Chemistry, 12(10), 1826. https://​doi.​org/​10.​1039/​c0036​
66h.
ReCiPe | PRé Sustainability (2019). [accessed 2019 Oct 9]. https://​www.​pre-​susta​inabi​lity.​com/​recipe.
ReCiPe method for the impact assessment (2011). https://​www.​rivm.​nl/​en/​Topics/​L/​Life_​Cycle_​Asses​
sment_​LCA/​ReCiPe.
Ren, J., Manzardo, A., Mazzi, A., Zuliani, F., & Scipioni, A. (2015). Prioritization of bioethanol produc-
tion pathways in China based on life cycle sustainability assessment and multicriteria decision-mak-
ing. The International Journal of Life Cycle Assessment, 20(6), 842–853. https://​doi.​org/​10.​1007/​
s11367-​015-​0877-8.

13
Comparing the environmental impacts of paracetamol dosage… 12465

Renteria Gamiz, A. G., De Soete, W., Heirman, B., Dahlin, P., De Meester, S., & Dewulf, J. (2019).
Environmental sustainability assessment of the manufacturing process of a biological active phar-
maceutical ingredient. Journal of Chemical Technology & Biotechnology, 94(6), 1937–1944.
https://​doi.​org/​10.​1002/​jctb.​5975.
Reza, B., Sadiq, R., & Hewage, K. (2014). Emergy-based life cycle assessment (Em-LCA) for sustain-
ability appraisal of infrastructure systems: A case study on paved roads. Clean Technologies and
Environmental Policy, 16(2), 251–266. https://​doi.​org/​10.​1007/​s10098-​013-​0615-5.
Rodríguez, R., Espada, J. J., Pariente, M. I., Melero, J. A., Martínez, F., & Molina, R. (2016). Compara-
tive life cycle assessment (LCA) study of heterogeneous and homogenous Fenton processes for the
treatment of pharmaceutical wastewater. Journal of Cleaner Production, 124, 21–29. https://​doi.​
org/​10.​1016/j.​jclep​ro.​2016.​02.​064
Rybaczewska-Blażejowska, M., & Palekhov, D. (2018). Life cycle assessment (LCA) in environmen-
tal impact assessment (EIA): Principles and practical implications for industrial projects. Manage-
ment, 22(1), 138–153. https://​doi.​org/​10.​2478/​manme​nt-​2018-​0010.
Saur, K., Gediga, J., Hesselbach, J., Schuckert, M., & Eyerer, P. (1996). Life cycle assessment as an
engineering tool in the automotive industry. The International Journal of Life Cycle Assessment,
1(1), 15–21. https://​doi.​org/​10.​1007/​BF029​78626.
Savelski, M. J., Slater, C. S., Tozzi, P. V., & Wisniewski, C. M. (2017). On the simulation, economic
analysis, and life cycle assessment of batch-mode organic solvent recovery alternatives for the phar-
maceutical industry. Clean Technologies and Environmental Policy, 19(10), 2467–2477. https://​doi.​
org/​10.​1007/​s10098-​017-​1444-8.
Sharma, D., & Hussain, C. M. (2020). Smart nanomaterials in pharmaceutical analysis. Arabian Journal
of Chemistry, 13(1), 3319–3343. https://​doi.​org/​10.​1016/j.​arabjc.​2018.​11.​007.
Sharma, R. K., Pallakonda, S., Raju, G., Sarkar, P., Singla, E., & Singh, H. (2018). An approach to
evaluate sustainability of a production process based on its LCA and environment impact analysis:
A case study on a food product. Materials Today: Proceedings, 5(5), 12467–12473. https://​doi.​org/​
10.​1016/j.​matpr.​2018.​02.​226.
Sharma, R. K., Sarkar, P., & Singh, H. (2020). Assessing the sustainability of a manufacturing process
using life cycle assessment technique—a case of an Indian pharmaceutical company. Clean Technol-
ogies and Environmental Policy, 22(6), 1269–1284. https://​doi.​org/​10.​1007/​s10098-​020-​01865-4.
Siegert, M. W., Saling, P., Mielke, P., Czechmann, C., Emara, Y., & Finkbeiner, M. (2020). Cradle-to-
grave life cycle assessment of an ibuprofen analgesic. Sustainable Chemistry and Pharmacy, 18,
100329. https://​doi.​org/​10.​1016/j.​scp.​2020.​100329.
Singh, P. K., & Sarkar, P. (2019). A framework based on fuzzy AHP-TOPSIS for prioritizing solutions to
overcome the barriers in the implementation of ecodesign practices in SMEs. International Journal
of Sustainable Development & World Ecology. https://​doi.​org/​10.​1080/​13504​509.​2019.​16055​47.
Slater, C. S., & Savelski, M. J. (2009). Towards a Greener Manufacturing Environment. 78–83
Sousa, A. C., Veiga, A., Maurício, A. C., Lopes, M. A., Santos, J. D., & Neto, B. (2020). Assessment of
the environmental impacts of medical devices: A review. Environment Development and Sustain-
ability, 23, 9641–9666. https://​doi.​org/​10.​1007/​s10668-​020-​01086-1.
The Pharmaceutical Industry and Global Health. (2017). International Federation of Pharmaceutical
Manufacturers & Associations. https://​www.​ifpma.​org/​wp-​conte​nt/​uploa​ds/​2017/​02/​IFPMA-​Facts-​
And-​Figur​es-​2017.​pdf.
The Pharmaceutical Industry in Figures. (2017). European Federation of Pharmaceutical Industries and
Association. https://​www.​efpia.​eu/​media/​219735/​efpia-​pharm​afigu​res20​17_​stati​sticb​roch_​v04-​
final.​pdf.
Tillman, A. M., Ekvall, T., Baumann, H., & Rydberg, T. (1994). Choice of system boundaries in life
cycle assessment. Journal of Cleaner Production, 2(1), 21–29. https://​doi.​org/​10.​1016/​0959-​
6526(94)​90021-3.
Tridech, S., & Cheng, K. (2010). An investigation on the framework for EREE-based low carbon manu-
facturing. In: Responsive manufacturing-green manufacturing (ICRM 2010), 5th international con-
ference on responsive manufacturing, p. 257–267. http://​ieeex​plore.​ieee.​org/​xpls/​abs_​all.​jsp?​arnum​
ber=​56291​81.
Vinodh, S., Ben Ruben, R., & Asokan, P. (2016). Life cycle assessment integrated value stream mapping
framework to ensure sustainable manufacturing: A case study. Clean Technologies and Environ-
mental Policy, 18(1), 279–295. https://​doi.​org/​10.​1007/​s10098-​015-​1016-8.
Vozzola, E., Overcash, M., & Griffing, E. (2018). Life cycle assessment of reusable and disposable
cleanroom coveralls. PDA Journal of Pharmaceutical Science and Technology, 72(3), 236–248.
https://​doi.​org/​10.​5731/​pdajp​st.​2017.​007864.

13
12466 R. K. Sharma et al.

Welz, T., Hischier, R., & Hilty, L. M. (2011). Environmental impacts of lighting technologies—Life cycle
assessment and sensitivity analysis. Environmental Impact Assessment Review, 31(3), 334–343. https://​
doi.​org/​10.​1016/j.​eiar.​2010.​08.​004.
Wernet, G., Conradt, S., Isenring, H. P., Jiménez-González, C., & Hungerbühler, K. (2010). Life cycle
assessment of fine chemical production: A case study of pharmaceutical synthesis. The International
Journal of Life Cycle Assessment, 15(3), 294–303. https://​doi.​org/​10.​1007/​s11367-​010-​0151-z.
Williams, A. S. (2009). Life cycle analysis: A step by step approach. Champaign, IL: Illinois Sustainable
Technology Center. [accessed 2016 Mar 8]. http://​www.​ideals.​illin​ois.​edu/​handle/​2142/​14450.
Yee, K. F., Tan, K. T., Abdullah, A. Z., & Lee, K. T. (2009). Life cycle assessment of palm biodiesel:
Revealing facts and benefits for sustainability. Applied Energy, 86, S189–S196. https://​doi.​org/​10.​
1016/j.​apene​rgy.​2009.​04.​014.
Zaid, A., Rinno, T., Jaradat, N., Jodeh, S., & Khammash. (2013). Interchangeability between paracetamol
tablets marketed in Palestine. Is there a quality reason for a higher price? Eastern Mediterranean
Health Journal, 19(6), 542–546. https://​doi.​org/​10.​26719/​2013.​19.6.​542.
Zanjirani Farahani, R., Asgari, N., & Davarzani, H. (Eds.). (2009). Supply chain and logistics in National,
International and Governmental environment. Heidelberg: Physica-Verlag HD. https://​doi.​org/​10.​
1007/​978-3-​7908-​2156-7.
Zerazion, E., Rosa, R., Ferrari, E., Veronesi, P., Leonelli, C., Saladini, M., & Ferrari, A. M. (2016). Phyto-
chemical compounds or their synthetic counterparts? A detailed comparison of the quantitative envi-
ronmental assessment for the synthesis and extraction of curcumin. Green Chemistry, 18(6), 1807–
1818. https://​doi.​org/​10.​1039/​C6GC0​0090H.

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