Ultraviolet-Visible Methods in Pharmaceutical Production and Analysis

This report delves into Ultraviolet-Visible (UV-Vis) methods, a crucial technique in the pharmaceutical industry. It details the working principles of UV-Vis spectroscopy, explaining how it measures absorbance and luminous intensity to analyze substances. The report highlights its widespread use in drug detection, content determination, and impurity analysis, providing examples from pharmacopoeias worldwide. Furthermore, it explores the advantages of UV-Vis, such as high accuracy, sensitivity, and ease of operation, while also addressing its limitations. The report also discusses the future potential of UV-Vis in Pharma, including its application in continuous manufacturing processes and real-time quality control, emphasizing the monitoring of critical process parameters (CPP) and their impact on critical quality attributes (CQA). The report concludes by presenting a schematic diagram of a continuous flow operation for tablet production, illustrating the integration of UV-Vis methods for drug content and stability measurements, thus showcasing its vital role in ensuring drug quality and efficacy throughout the pharmaceutical production process. References are included.

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Ultraviolet - Visible methods
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A. How does it work (include overview and some detail)
Spectrophotometry is a method for qualitative and quantitative analysis of the substance by
measuring the absorbance or luminous intensity of the substance at a specific wavelength or
within a certain wavelength range. The wavelength range measured in this experiment is 200 ~
800nm (Gorog 2017).
When the monochromatic light radiation passes through the solution of the substance to be
tested, the amount absorbed by the substance within a certain concentration range is proportional
to the concentration of the substance and the thickness of the liquid layer (optical path length)
(Gorog 2017).
Spectroscopic research methods occupy leading positions in chemistry, biology,
pharmaceuticals and other fields. They are used to determine the composition of complex
compositions, the state of living organisms, control product quality, study the structure of
substances, etc. The use of spectroscopic methods is based on the interaction of molecules of a
substance with electromagnetic radiation, resulting in the absorption, emission or scattering of
part of the energy, which is recorded in the form of the corresponding spectrum (Gorog 2017).
UV spectroscopy uses a shorter wavelength region (400-700 nm) of electromagnetic
radiation, which has a higher energy, which causes electronic transitions in the molecule.
Functional groups or systems that are called chromophores are observed in the UV spectra.
Usually they have p-electrons or free electron pairs of heteroatoms, the transition of which from
the ground to the excited energy level corresponds to the UV range. Chromophores are part of
proteins and nucleic acids; therefore, UV spectroscopy is widely used in biochemical studies.
B. What and where is it being used in the Pharma industry?

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Medicines are special products related to human health. The production process of medicines
has clear and standardized management from raw materials, production processes, equipment,
software to personnel operations. Safe, effective and controllable are the only criteria for
evaluating the quality of medicines. In order to ensure that pharmaceutical production meets the
requirements of pharmaceutical quality, modern pharmaceuticals are subject to various methods
of detection and monitoring throughout the production process of intermediates and finished
products, such as high-performance liquid chromatography, gas chromatography, ultraviolet
spectrophotometer, etc. It is a commonly used testing instrument in pharmaceutical production.
Among them, due to the advantages of high accuracy, low measurement limit, simple equipment,
low instrument cost, and easy operation , the ultraviolet spectrophotometer has become one of
the necessary testing equipment in pharmaceutical production (Fernando 2016).
Ultraviolet spectrophotometry is a method for qualitative and quantitative analysis of
substances by measuring the absorbance or luminous intensity of substances at certain specific
wavelengths or within a certain range. The theoretical basis is Lambert-Beer law, the absorbance
and absorbance of solutions. The product of substance content and liquid layer thickness is
proportional to the product. For the general ultraviolet spectrophotometry, the relative error of
the measurement is 1% ~ 3%. With the synthesis and application of a large number of new color
developing agents, especially the application research on multi-component complexes and
various surfactants, the sensitivity of element determination has been greatly improved. Using
pre-enrichment and differential method, the applicable mass fraction is from constant (1% ~
50%) to trace amount (10 -1 ° ~ 10 -8 ) (Fernando 2016).
In the pharmacopoeia of various countries, the application examples of ultraviolet
spectrophotometry can be seen in various items such as physical and chemical constants,

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identification, inspection and content determination of drugs . At present , the types of drugs
analyzed by ultraviolet spectrophotometer are vitamins, antibiotics, antipyretics, analgesics,
blood pressure lowering drugs, tranquilizers, antitussives, eye drops, sulfonamides, diuretics,
certain gynecological drugs, Dysentery drugs, diarrhea drugs, anti-tumor drugs, anti-tuberculosis
drugs, etc.
The items that use ultraviolet spectrophotometry in pharmacopoeia and pharmaceutical
standards include absorption coefficient, identification, color inspection, purity inspection,
dissolution, content uniformity inspection, and content determination. In pharmaceutical
production, the most widely used ultraviolet spectrophotometry is the determination of drug
content, drug impurity detection, drug stability investigation, release rate, drug loading behavior
determination and substance structure identification.
The content of medicines is one of the main indicators for evaluating medicines. When
designing its determination method, the choice of the determination method should focus on
accuracy, stability and repeatability. The UV spectrophotometer is easy to operate, has high
accuracy and repeatability, and can now be used directly for the detection of drug content. At
present, most of the pharmaceutical dosage forms detected by ultraviolet spectrophotometer
include tablets, ointments and injections.
C. Where might it be used in Pharma in the future?
UV-VI spectrophotometer would have a variety of uses in Pharma in the future. One of the
uses is verification substance. This is achieved through comparison with standard and standard
spectrum .Another use is purity test. It can also be used in speculation of molecular structure of

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compound. Lastly, it can be used to in complex composition and Determination of stability
constant
D. What are the advantages and disadvantages of using this form of measurement in
Pharma?
Compared with other methods, ultraviolet-visible spectrophotometry is easy to operate,
has high sensitivity, good selectivity, and has little or no interference. Especially in recent years,
due to the application of new technologies and new methods, such as: derivative spectroscopy,
factor analysis, dual-wavelength and three-wavelength methods, differential photometry,
artificial neural network, etc., combined with ultraviolet-visible spectrophotometry , Making
UV-Vis spectrophotometry widely used in drug analysis, broadening the application of UV-Vis
spectrophotometry in drug analysis. It should also be noted that UV-Vis spectrophotometry is
suitable for continuous production. With UV-Vis spectrophotometry, pharmaceutical engineers
can gradually monitor the operation of the process during the unit operation. This tool is the key
to continuous process development. In addition, the quality of the product and the process are
always monitored during the operation of the process, so all raw materials, intermediate
products, and final products are monitored. The quality control mode is more reliable than the
end point quality control mode used in the batch process, because the end quality control mode
will bring many sources of variation and errors, such as sampling. This fundamental difference
makes continuous processes more popular. The disadvantage is that it can only be operated by
experts in the field (Perkampus 2013).
Part 2

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Ultraviolet-visible spectroscopy is widely used in drug detection and analysis because of
its high sensitivity, high accuracy, good selectivity, and simple operation. Ultraviolet-visible
spectrophotometer mainly includes light source, monochromator, absorption cell, detector and
signal processing system. This method is mainly used for quantitative analysis of substances, and
is also an auxiliary method for qualitative analysis and structural analysis (Fernando 2016).
UV-Vis spectrophotometer can be used for impurity detection. Impurities refer to
substances present in medicines that have no therapeutic effect or affect the stability and efficacy
of medicines, and even substances that are harmful to human health. Using the difference in the
selective absorption properties of drugs and impurities for light, if the drug does not absorb at the
maximum absorption wavelength of the impurities, the absorbance of the sample solution can be
measured at this wavelength, and the amount of impurities can be controlled by controlling the
absorbance of the sample solution (Perkampus 2013).
The schematic diagram below shows the continuous process of drug production. The UV-
Vis Spectrophotometer is introduced at synthesis stage where it is used to measure drug content
and the hot melt extrusion stage where it is used to measure drug stability.
(
Figure 1. Continuous process from beginning to end.
CPP aspects controlled and desired impact of CQA

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One of the CPP aspects controlled is drug stability test. The stability of pharmaceutical
preparations refers to the speed and degree of changes in the quality of pharmaceutical
preparations from preparation to use. It is one of the important indicators for evaluating the
quality of pharmaceutical preparations. It is an important basic research content for the safety
and effectiveness of pharmaceuticals.
The second aspect controlled is drug content. To measure the drug content in the solid
preparation by ultraviolet spectrophotometry , it is necessary to prepare a standard solution and a
sample solution of known content to determine the wavelength at the maximum absorbance; then
use the content as the abscissa and the absorbance as the ordinate to perform linear regression
and establish a standard curve ; Take an appropriate amount of the prepared sample solution,
place it in a quartz cuvette, measure the absorbance of the solution at the wavelength of
maximum absorbance, and calculate the content in the sample through the standard curve.
Conclusion
All in all, the ultraviolet-visible spectrophotometer has the advantages of fast, accurate
and stable, which has been deeply developed and applied in the field of drug production
monitoring. With the development of various new instruments and modern technology, the UV
spectrophotometer will also develop towards the cutting-edge technology with more trace and
more sensitive. At that time, its application in drug production monitoring.

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Reference
Fernando J. M. (2016). Continuous Manufacturing [Lecture material]. Department of Chemical
and Biochemical Engineering, Rutgers University, New Jersey, USA.
Gorog, . (2017). Ultraviolet Visible Spectrophotomet. Taylor & Francis.
Perkampus, H.-H. (2013). UV-VIS spectroscopy and its applications. Berlin: Springer-Verlag.