Here is an outline on the occurrence of active pharmaceutical ingredients (APIs) in fish and amphibians:

I. Introduction

- Brief overview of active pharmaceutical ingredients (APIs) and their widespread use

- Importance of aquatic ecosystems and the potential impact of APIs on aquatic life

II. Sources of API contamination in aquatic ecosystems

- Human pharmaceutical use and disposal

- Agricultural runoff and veterinary use

- Industrial effluent and wastewater treatment plants

III. Occurrence of APIs in fish

- Examples of APIs detected in fish tissues (e.g. antidepressants, antibiotics, hormones)

- Factors influencing API accumulation in fish (e.g. species, habitat, diet)

- Potential effects of API exposure on fish physiology and behavior

IV. Occurrence of APIs in amphibians

- Examples of APIs detected in amphibian tissues (e.g. painkillers, anti-inflammatory drugs)

- Factors influencing API accumulation in amphibians (e.g. habitat, diet, life cycle)

- Potential effects of API exposure on amphibian development and survival

V. Environmental and ecological implications*

- Potential for API-induced changes in aquatic food webs and ecosystem dynamics

- Implications for human consumption of contaminated fish and amphibians

VI. Conclusion

- Summary of key points

Introduction.

Active pharmaceutical ingredients (APIs) are the chemical-based compounds that have produced mainly
in the countries the USA, Europe, China, and India. APIs have pharmacological activity mainly used with
combination of other ingredients to diagnose, cure, mitigate, and treat the disease. However, in the
recent past years, many medicinal-based corporations have started importing these substances from
countries producing active ingredients to their home countries. Modern day medicines have been used
by people to prevent, treat, diagnose, and cure disease. Every single medication is composed of two
main components, i.e. the API, which is the major component, is chemically and biologically active that
has to do the work in your body and other component known as excipients like lactose or mineral oil in
the pill, which is chemically inactive that provides, e.g. volume, a sweet flavor, or a color. These
excipients helps in the delivery of APIs in the body system. Numerous chemical compounds and raw
materials are utilized in multi-step reaction to make an API. However, their main purpose is to treat the
disease directly by acting upon (via their pharmacological activity) along with combination of inactive
form. Nearly more than 1 lakh tones of pharmaceutical products are consumed all over the globe (e.g.
Europe alone covers up to 24% of the consumption of medicinal products). Therefore, the generation of
these APIs has stimulated the release of chemicals in the environment and thereby lead to the spreading
of pollution. Concurrently, this enormous generation of pollution has called the worldwide attention
that requires an immediate alteration in the policies and regulations.

Thereby, considering the negative impacts of these chemical channels that are responsible for
generating API, the pharmaceutical companies are rendering approval to the microbial-based
fermentation using bacteria or yeast bial-based biopharmaceuticals created the returns of around $100
billion in 2017, and the business is escalating at a substantial pace (6% CAGR) [5,6]. It is predicted that in
the year 2020 the market demand for fermentation-based protein drugs is expected to reach $60 billion
from $44 billion. Similarly, the demand of peptide hormones and vaccine, which was $10–19 billion,
respectively, is expected to reach $18–28 billion. Today pharmaceutical companies such as Bayer,
AbbVie, Biocon, GlaxoSmithKline, Eli Lilly, Sanofi, and Merck are depending upon microbial schemes and
arrangements for the production of biopharmaceutical products. In this review, the focused has been
laid upon the current and modern developments that taken place in chemical route of processing of
biomass relative to traditional methods with emphasis on the production of APIs.

things hazardous to human, water bodies (including drinking water), and other bio-based lives owing to
their uncontrolled contact to the environment . Furthermore, the presence of these compounds has
been detected in the trace levels from nanograms to micrograms in the last span of 10 years from
ground water, drinking water, and waste water . The recent finding was reported on the pervasiveness
of enormous amount of around 18 APIs in the Lake Victoria-Uganda (in the amount of 5600 ng
L−1) .Thereby, these APIs have been established as global contaminants. Although the formation of
these chemical compounds is not from the single source of reaction, rather, they are developed from
many chemical components that are usually initiated from a single intermediate . Furthermore, several
intermediates are formed during the process in order to convert any raw material into an API. These
several reactions usually pass through the long channels of purification during their developmental
engineering, which involves the usage of huge reactors . Concurrently, these APIs are then checked for
their purity before they are being sold to the drug manufacturers.

In order to generate the chemicals, one of the major biomasses is the carbohydrates, which constitute
about the largest (95%) amongst the organic compounds of the planet. These are basically exploited for
producing further products either using fermentation or chemical alteration. Biomass in the form of
starch, cellulose, hemicellulose, pectin, and lignin usually exists in the form of feedstock . In the earlier
era of traditional processing starch and other carbohydrate-rich feedstock were usually being exploited
as a raw material by the vivid chemical industries. Undoubtedly, various products in the form of
chemical and polymers can be generated by using any alteration in the procedure (fermentation) in
order to achieve the desired derivative nation toward production of fuel, which is more than the
conversion to xylose and glucose . Since the earth’s biomass is largely composed of lignocellulose and
thus the entire crop left over in terms of wheat and rice straw, sugarcane bagasse and fibers of corn
husk are classified underneath of it. These crops are made of lignin, hemicellulose, and cellulose, which
are collectively called as lignocellulosic material. These lignocellulosic materials are processed by various
techniques, viz. chemical, thermal, or biological; they are converted into sugars, chemicals, or ethanol.

But in order to breakdown these lignocellulosic materials, some pretreatment in the form of hydrolysis,
delignification like the usage of sulfuric acid, alkaline treatment, high-temperature steaming, and
pressure-based homogenization are generally required for distorting the structured and organized
plants-based structure . Therefore, after the application of pretreatments of these lignocellulosic
materials, they can be readily converted to desired intermediates. In order to reduce the steps of
production or to reduce the cost by keeping the safety of the environment, we need to cross the various
technological and economic barriers for employing the potential applications of lignocellulosic
materials .

A number of multiple published reports focus on the production of ethanol rather than other product .
Thereby, there are limited number of life cycle assessments (LCAs) that can generate multiple products.
However, from the perspective of environments as well as economic, most of the bio-based fuels and
bioresources that are produced under the one canopy of the factories are still not a promising option.
Similarly, forestry-based biorefinery system is one of the specific examples . Concurrently, there are a
number of key factors that have been recognized considering the environment-favored performance for
the generation of bioethanol and biodiesel. In order to carry out the united production of chemicals, a
widened and well-adapted spectrum is needed. Nevertheless, there are still certain gaps of reasonable
prices that are required for the creation of large-scale biorefineries. Furthermore, the chemical
properties of biomass are not always favorable to biomass-based raw material; therefore, new
technologies are demanding and challenging amongst the existing companies.

Also, propionic acid and its related esters are produced in the amount of approximately 192,000 tons
throughout the year and also have several applications in the chemical industry (e.g. for the production
of thermoplastics, solvents in paints and resins as well) and in the usage of. animal feeds Further, from
the viewpoint of biorefinery its production can be elevated for the fermentation of glycerol and sugar
Also, economically, the conversion of glucose to propionic acid is anticipated to be 15% less than the
conversion of glycerol. Likewise, the other related upcoming feasibility is to employ the fermentation of
glycerol for the production of 3-hydroxypropionic acid, which is an essential building-block chemical
Secondly, it can be converted to 3-hydroxypropionic acid to acrylic acid, which comparatively has better
environment-based functioning. Concurrently, researchers from the National Renewable Energy
Laboratory have reported the development of an innovative pretreatment by employing the use of an
organic solvent in combination with water for the clarification of lignin and sugars derived from chemical
nature .

Moreover, the contemporary revolution in the advanced technologies (e.g. genetic and metabolic
engineering, enzymatic engineering) has opened up new avenues for creating vivid types of industry-
based products such as APIs from raw materials derived from plant . Owing to the preferential use of
renewable raw materials of biomass by the APIs’ chemical industries, the concept of biorefinery has
emerged and can be executed to produce different bioproducts with the replacement of chemical-based
manufacturing . Renewable resources are good sources as substrate for the production of green
chemicals, APIs, and key starting materials (KSMs), which come under a vast subject. Therefore, the
presented review entirely covers the major developments and possibilities of lignocellulose as feed
stock that occurred in the recent years in the capacities of renewable biomass as a prominent
foundation of chemicals and their related converted products.

Presently, owing to the considerable increase in the pollution threat to the environment, more and
more API-producing companies have been urged to follow the greener path in order to reduce the
generation of waste (in terms of chemicals, solvents as by-products) . Whereas API-producing
companies are always looking for the faster and economical methods, however, in reality, if we tend to
bring down the generation of waste, then the number of steps for producing API has to be reduced.
Because few and less tangible steps is the primary requisite with production of solvents or chemicals
generated for producing a single pure molecule of API. Likewise, in addition to cut down the steps,
manufactures are further needed to select nonhazardous types of solvents that possess the ability of
producing proficient and effectual results. Thereby, in order to achieve the results on greener guidelines,
manufacturing companies should employ contract development officers (CMOs) and further pass their
product through the services of contract development and manufacturing organization (DCMOs) so that
the formulation of the process of API can be planned out at an early stage with the help of additional
screening to avoid unavoidable changes or alteration in the later stage. This can be accomplished by
following the protocols of scale-up processing in the pilot plants where thorough supervision needs to
be administered for assessing time-to-time assessment and quality control. However, the establishment
of such a kilo lab comes with potential challenges of good manufacturing practices (GMPs) that require
planned budget and diligent supervision. And, by following these measures, we can reduce the
exploitation of raw materials and generation of by-products.

Concurrently, in the last year’s vivid methods of organic synthesis have been employed for generating
pharmaceutical products, which has strengthened the medical sector by reducing the causalities,
illnesses, and death. However, in order to achieve this accomplishment, if we are deteriorating the
environment simultaneously then all the efforts of pharmaceutical chemists will go in vain. Therefore,
the pathway of green chemistry is utmost desirable for minimizing the dreadful impact on the
environment. It is widely known that 80% of the wastage in the form of by-product by the
pharmaceutical industry is related to the solvent reported by GlaxoSmithKline . Thus, the production of
the significant amount of the contaminated solvents will generate the air and other pollutants.

These ways can only be achieved through employing the use of sustainable tools. These tools call for the
nib-to-nib strategy-based research that involves the following steps in making the processes threat free.
The ways of biomass-generated feedstocks, their bioconversion routes, use of selected harmless
chemicals, and channelized ways of technical processing are the key parameters that can lessen the
environmental issues to the minimal. Similarly, the inline concept of integrated biorefinery and the
continuous use of biosubstrates with the consumption of nonrenewable sources can safeguard the
environment with a profound relevance . In order to satisfy these parameters, the methodology of LCA
needs to be persuaded that consisted of complete assessment of the products and processes from start
to the end and quantify each environment-based quantification. Therefore, the only way to drop down
the expanding problem is the generation of green manufacturing practices from pharmaceutical
industries with thorough attentiveness on the selection, use, recovery, and disposal of the chemicals.