The document discusses drug-excipient compatibility studies. It notes the importance of such studies in maximizing stability and avoiding formulation problems. The goals are outlined as determining which excipients stabilize drugs and assigning risk levels. Mechanisms of interaction include physical interactions like complexation or adsorption, and chemical interactions like hydrolysis or oxidation. Analytical methods to detect interactions include thermal techniques like DSC and microcalorimetry, and spectroscopic techniques like IR and Raman spectroscopy. The document provides details on several of these techniques.
it provide a brief note on the drug excipient interaction and various technique to find it which is a part of preformulation studies. it gives help to mpharm(pharmaceutics) students. i.
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
it provide a brief note on the drug excipient interaction and various technique to find it which is a part of preformulation studies. it gives help to mpharm(pharmaceutics) students. i.
WHAT IS COMPRESSION ?
Compression means reduction of bulk volume of material as a result of the removal of gaseous phase (air) by applied pressure
WHAT IS CONSOLIDATION?
Consolidation is an increase in mechanical strength of material resulting from particle - particle interactions.
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Physics of Tablet compression is very useful during study of the tablet. It contains the mechanism of tablet compression. It also contains the process of tablet compression.
What is dissolution? Dissolution is a process in which a solid substance get solubilizes in a particular solvent to yield a solution i.e. mass transfer from the solid surface to the liquid phase.
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
Drug Excipient Interaction, Different Methods, Stability Testing.
drug excipient Compatibility and Incompatibility, Goals of drug excipient compatibility Methods, Factors Influencing stability Testing, Significant changes that might occur during satability Analysis
This presentation includes the detail information about the physics of tablet compression and compaction, Compression, Effect of friction, distribution of forces, compaction profiles,solubility.
Physics of Tablet compression is very useful during study of the tablet. It contains the mechanism of tablet compression. It also contains the process of tablet compression.
What is dissolution? Dissolution is a process in which a solid substance get solubilizes in a particular solvent to yield a solution i.e. mass transfer from the solid surface to the liquid phase.
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
Drug Excipient Interaction, Different Methods, Stability Testing.
drug excipient Compatibility and Incompatibility, Goals of drug excipient compatibility Methods, Factors Influencing stability Testing, Significant changes that might occur during satability Analysis
Introduction,Drug- Excipient Compatibility Experimental Design ,Excipient role in drug destabilization,DRUG EXCIPIENT COMPATIBILTY IN PARENTERAL PRODUCTS.This topic are described.
Upon completion of module on Google classroom you will able to
1. Understand concept of Google Classroom.
2. Create your own class using Google Classroom.
3. Invite students and teachers to join Google Class.
4. Add topics and course content in Classroom.
5. Create and conduct assignments for students.
6. Post announcements and notices.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
1. Modern Pharmaceutics
Dr. Kailas Mali
Professor in Pharmaceutics,
Adarsh College of Pharmacy, Vita
Drug Excipient Interactions
2. 1. Importance of Drug-Excipient compatibility studies
2. Goals of Drug-Excipient compatibility studies
3. Mechanism of Drug-Excipient(s) interactions
4. Analytical Methods for Drug – Excipient Incompatibility
1. Thermal Techniques
2. Spectroscopic Techniques
3. Chromatographic Techniques
Contents
3. ● Excipients can initiate, propagate or
participate in chemical or physical
interactions with an active substance,
possibly leading to compromised quality
or performance of the medication.
● Study of drug-excipient compatibility is
an important phase in the pre-
formulation stage of drug development.
● The potential interactions between drugs
and excipients have effects on the
chemical, physical, bioavailability and
stability of the dosage form.
Importance of Drug-Excipient compatibility
studies
● It maximizes the stability of a dosage
form.
● It bridges drug discovery and
development.
● It is essential in investigational new drug
(IND) submission.
● It helps to avoid surprise problems during
formulation processes.
Introduction
4. Goals of Drug-Excipient compatibility
studies
● To find out how compatible an excipient
is with API or candidate drug molecules.
● To find out the excipient that stabilizes
an unstable API.
● To assign a relative risk level to each
excipient.
● To design and develop selective and
stability indicating analytical methods to
determine their impurities.
Types of Drug-Excipient(s) interactions
● Intentional (desirable) interactions
● Unintentional (undesirable) interactions
Mechanism of Drug-Excipient(s)
interactions
● Physical drug-excipient interactions
● Chemical drug-excipient interactions
● Physiological/Biopharmaceutical drug-
excipient interactions
Introduction
5. ● Quite common but are very difficult to
detect.
● Interact without undergoing changes
involving breaking or formation of new
bonds.
● The components retain their chemical
structure but undergo changes which
alter their physical properties.
● Physical interactions may result in
changes in dosage uniformity, colour,
odour, flow properties, solubility,
sedimentation rate, dissolution rate etc.
● Incompatibilities are assessed by
physically observing the test samples.
● Physical interactions can be either
beneficial or detrimental to the product
performance depending on its
application.
Physical drug-excipient interactions
6. ● Improves bioavailability of sparingly
water-soluble drugs: using complexing
agents (e.g., complexation of
cyclodextrin with ursodeoxycholic acid)
increases the rate and extent of drug
dissolution.
● Increases surface area of drugs available
for dissolution: Adsorption of drugs on
excipient surface can increase the
surface area of the drug available for
dissolution (e.g., formulation of
indomethacin using kaolin as adsorbent).
● Improves dissolution rate and
bioavailability of hydrophobic
drugs: Physical interactions of drugs with
excipient improve the dissolution rate
and bioavailability of hydrophobic
drugs.(e.g., solid dispersions of
piroxicam, norfloxacin, nifedipine and
ibuprofen using polyethylene glycol of
different molecular weights).
Benefits of Physical drug-excipient interactions
7. ● Decreases dissolution and absorption
rates of drug substances due to the
formation of insoluble complexes (e.g.,
tetracycline forms an insoluble
complex with calcium carbonate;
Formulation of chlorpromazine with
polysorbate 80 and SLS decreased
membrane permeability of the drug).
● Slow dissolution of drugs: due to Ion
interactions. (e.g., solid dispersion of
povidone and stearic acid in a capsule
showed slow dissolution of the drugs.
● Reduces bioavailability of drugs
available for dissolution: Adsorption of
drugs on excipient surface can also
lead to reduced bioavailability. (e.g., the
marked reduction in the antibacterial
activity of containing cetyl pyridinium
chloride is due to the adsorption on the
surface of magnesium stearate in
tablets).
Detrimental effects of physical drug-excipient
interactions
9. ● Interaction through chemical degradation
pathway to produce an unstable
chemical entity.
● Generally, chemical interactions have a
deleterious effect on the formulation
hence; such kind of interactions must be
avoided.
● Chemical interactions can be in the form
of hydrolysis, oxidation, racemization,
polymerization, Maillard reactions,
photolysis etc.,
Some examples of chemical drug-excipient
interactions include
● Inhibition of diclofenac sodium release
from matrix tablet by polymer chitosan at
low pH. This occurs possibly via
formation of ionic complex between
diclofenac sodium and ionized cationic
polymer.
● Oxidation of diethylstilbestrol to the
peroxide and conjugated quinone
degradation products by Silicon dioxide
which acts as a catalyst.
Chemical drug-excipient interactions
10. Hydrolysis
● The most susceptible drugs are those
containing carbonyl groups like esters,
amides lactones, etc. with a good leaving
group.
● The reaction involves the addition of
water molecules and splitting the parent
drug into two parts.
● The presence of excipients may promote
the reaction either directly or by altering
the aqueous environment or affecting
other parameters such as pH, ionic
strength, or dielectric constant.
● Influence of water availability on
hydrolysis rates in aspirin compacts
containing dibasic calcium phosphate
dihydrate degrade approximately 10
times faster than formulations containing
lactose and two-fold faster than
formulations containing microcrystalline
cellulose.
Chemical drug-excipient interactions
11. Oxidation
● Reaction that increases the content of
more electronegative atoms in a
molecule. Electronegative heteroatoms
are generally oxygen or halogens.
● It can be catalyzed by oxygen, heavy
metal ions, and light, leading to free
radical formation (induction).
● Free radicals react with oxygen to form
peroxy radicals which in turn interact with
the oxidizable compound (propagation).
● Aldehydes, alcohols, alkaloids, and
unsaturated fats are of most susceptible
to oxidation.
● Excipients can be a source of oxidants
and metals.
● Excipients can also be involved in
generating mobile oxidative species such
as peroxyl radicals, superoxide, and
hydroxyl radicals.
● Many excipients contain impurities like
peroxides, aldehydes, organic acids,
reducing sugars.
● Raloxifene hydrochloride under went
oxidation to the N-oxide derivative in the
presence of povidone and crospovidone
due to peroxide impurities.
Chemical drug-excipient interactions
12. Maillard reaction
● Form colored pigments from sugars and
amines.
● Primary amines in the formulation with
carbonyl compounds, basically reducing
sugars, undergo Maillard reaction.
● Metoprolol + Lactose
Isomerisation
● Isomerization involves the conversion of
a chemical into its optical or geometric
isomer.
● Isomers may have different
pharmacological or toxicological
properties.
● For example, the activity of Levo (L) form
of adrenaline is 15-20 times greaterthan
for the Dextro (D) form.
Chemical drug-excipient interactions
13. Polymerization reaction
● Occur as a result of intermolecular
reactions lead to dimeric and higher
molecular weight species.
● Concentrated solutions of ampicillin,
aminopenicillin, progressively form dimer,
trimer, and ultimately polymeric
degradation products.
● Some organoleptic agents also may
undergo polymerization degradation.
● An example is the natural color Betalains
which is susceptible to color fading or
browning due to subsequent
polymerization
Chemical drug-excipient interactions
14. ● Interactions that occur after the drug
product has been administered to the
patient.
● Differ from physical interactions in the
following aspects-
● The interaction is between the medicine
(drug substance and excipients) and the
body fluids.
● The interactions have the tendency to
influence the rate of absorption of the
drug.
● Physiological interactions can be
detrimental to the patient.
● Increasing gastric pH by antacids
affecting enteric coat integrity.
● Interaction of tetracycline with calcium
ions forming unabsorbable complex.
● Increasing GI motility by sorbitol and
glycols which affect drug transit time and
absorption.
Physiological drug-excipient interactions
15. ● The key to the early assessment of
instability in formulations is the
availability of analytical methods to
detect low levels of degradation
products, generally < 2%.
1. Thermal Techniques
a. Differential Scanning Calorimetry (DSC)
b. Isothermal microcalorimetry
c. Differential Thermal Analysis (DTA)
2. Spectroscopic Techniques
a. Vibrational spectroscopy
b. Flourescence Spectroscopy/ Fluorometry/
Spectrofluorometry
3. Chromatographic Techniques
a. Thin Layer Chromatography (TLC)
b. High Performance Liquid Chromatography
(HPLC)
Analytical Methods of Detection
16. ● Comprise a group of techniques in which
the physicochemical properties of drug
substances are measured as a function
of temperature.
● The test samples are subjected to a
controlled temperature over a given
period of time.
● Plays a vital role in drug-excipient
compatibility studies and has been
frequently used for quick identification of
physicochemical interaction between
drugs and excipients.
Differential Scanning Calorimetry
● In this technique, the DSC curves of pure
samples are compared to that obtained
from 50% mixture of the drug and
excipient (usually 5mg of the drug in a
ratio of 1:1 with the excipient).
● It is assumed that the thermal properties
(melting point, change in enthalpy, etc.)
of blends are the sum of the individual
components if the components are
compatible with each other.
Thermal Techniques
17. ● An absence, a significant shift in the
melting of the components or
appearance of a new exo/endothermic
peak and/or variation in the
corresponding enthalpies of reaction in
the physical mixture indicates
incompatibility.
● However, slight changes in peak shape
height and width are expected due to
possible differences in the mixture
geometry.
●
Thermal Techniques
18. Advantages of Differential Scanning
Calorimetry
● Requires short time of analysis
● Low sample consumption
● Provides useful indications of any
potential incompatibility
Limitations of Differential Scanning
Calorimetry
● Conclusions based on DSC results alone
may be misleading and have to be
interpreted carefully.
● DSC cannot be used if thermal changes
are very small. Therefore, it should
always be supported by some non-
thermal methods like TLC or FT-IR or
XRPD.
● DSC cannot detect the incompatibilities
which might occur after long-term
storage.
Thermal Techniques
19. Isothermal microcalorimetry
● Extremely sensitive and invaluable tool to
determine incompatibilities.
● It measures minute amounts of heat
emitted or absorbed by a sample in a
variety of processes.
● Is used to characterize pharmaceutical
solid to obtain heats of solution, heats of
crystallization, heats of reaction, heats of
dilution and heats of adsorption – since
nearly all physicochemical processes are
accompanied by a heat exchange within
their surroundings.
● In a typical drug-excipient compatibility
study, a solution, suspension, or solid
mixture of drug substance and excipient
is placed in the calorimeter and the
thermal activity (heat gained or evolved)
at a constant temperature is monitored.
● The thermal activity observed is
assumed to be proportional to the rate of
chemical and/or physical processes
taking place in the sample.
● The thermal activity of the test sample is
compared to the “non-interaction” curve
constructed from the control.
Thermal Techniques
20. ● If an experimentally significant difference
is observed, the excipient is considered
to be potentially incompatible with the
drug substance.
Advantages of Isothermal microcalorimetry
● Samples are not heated, and so the
changes are observed as it might
typically occur at ambient conditions.
● It is sensitive to small changes in heat
gained or evolved, thus small samples, or
slow processes, may be investigated.
● It gives meaningful results without
requirement of multiple sample
preparations
● Does not require long storage times, thus
saving valuable time and effort during the
formulation process.
Limitations of Isothermal microcalorimetry
● Isothermal microcalorimetry is not
discriminatory. The exact nature of the
transition must be known in order to
interpret the data.
Thermal Techniques
21. Differential Thermal Analysis
● An analytical technique in which the
changes in temperature between a test
sample and an inert reference under
controlled and identical conditions is
used to identify and quantitatively
analyze the chemical composition of a
substance.
● When the test sample and inert reference
are heated to a sufficient temperature,
the thermal changes in the test sample
which lead to the absorption or emission
of heat can be detected relative to the
inert reference (control).
● The differences in temperature are then
plotted against time, or against
temperature.
● Drug-excipient interactions can be
identified by comparing DTA curves
obtained from the test sample with those
of inert reference.
● Incompatibilities are indicated by the
appearance of one or more new DTA
peaks or the disappearance of one or
more DTA peaks corresponding to those
of the components of the test sample.
Thermal Techniques
22. Advantages of Differential Thermal
Analysis
● DTA technique yield data that are
considerably more fundamental in
nature.
● Enthalpy change (under a DTA peak) is
not affected by the heat capacity of the
sample.
Limitations Differential Thermal Analysis
● DTA is usually performed on powders
and for this reason, the resulting data
may not be representative of bulk
samples, where transformations may be
controlled by the buildup of strain energy.
● The rate of heat evolution may be high
enough to saturate the response
capability of the measuring system. This
limitation may be overcome by diluting
the test sample with inert material.
● Problems are encountered in transferring
heat uniformly away from the specimen
at temperature range of 200 to 500◦C.
This problem may be solved by using flat
disc-like thermocouples to ensure
optimum thermal contact with the now
flat bottomed sample container.
Thermal Techniques
23. ● Include all techniques which probe
certain features of a given sample by
measuring the amount of radiation
emitted or absorbed by molecular or
atomic species of interest.
● Uses electromagnetic radiation to
interact with matter and thus investigate
certain features of a sample as a
function of wavelength (λ).
● Because these methods of analysis use a
common set of optical devices for
collimating and focusing the radiation,
they often are identified as optical
spectroscopies.
● Most frequently used methods are
vibrational spectroscopy, diffuse
reflectance spectroscopy, fluorescence
spectroscopy, FT-IR spectroscopy etc.
● Each operates over different, limited
frequency ranges within the broad EM
spectrum, depending on the processes
and degree of the energy changes.
Spectroscopic Techniques
24. Vibrational Spectroscopy
● Using this method, information on the
molecular structure and environment of
organic compounds are generated by
measuring the vibrations of chemical
bonds that result from exposure to
electromagnetic energy at various
frequencies. These vibrations are
commonly studied by infrared and
Raman spectroscopies.
● IR & Raman Spectroscopy are
complementary to each other.
● The spectra obtained are indicative of the
nature of chemical bonds present in the
test sample, and when pieced together
can be used to identify the chemical
structure or composition of a given
sample.
Spectroscopic Techniques
Spectroscopy Range Measures
IR 4000 – 400
cm-1
Dipole moment
(direct absorption)
RAMAN 4000 – 10
cm-1
(practical)
Polarizability
(inelastic
scattering)
25. Spectroscopic Techniques
IR Spectroscopy Raman Spectroscopy
IR spectra result from light absorption by vibrating
molecules
Raman spectra result from scattering of light by vibrating
molecules
IR activity results from changing dipole moment Raman activity results from change of polarizability of a x
IR spectroscopy the range is limited to IR
frequencies
A monochromatic light beam of high intensity laser can be
used in UV, visible or IR regions in Raman measurements
Absorption signal is measured in the same direction
as the incident beam.
Scattered light is observed at right angles to the direction
of the incident beam
IR technique requires solid sample preparation using
KBr or permit direct observation of liquids, films and
gels.
Non-destructive. The sample can be measured directly in
glass container or in case of pharmaceuticals samples
can be measured in original sachets.
Less intense light source Highly intense focused laser source. Small samples
possible.
Less costly method More costly method
26. Advantages of vibrational spectroscopy
● Sensitive and can be used for process
monitoring.
● Requires short time of analysis
● Nondestructive method of analysis with
the exception of some UV-Vis
applications
● Requires minimal or no sampling
preparation (Raman spectroscopy)
● Provides complex fingerprint which is
unique to the compound under
investigation (IR & Raman spectroscopy).
Limitations of vibrational spectroscopy
● Presence of overlapping peaks in the
spectra may hinder the analysis.
● Solvent may interfere if samples are run
in solution (Raman spectroscopy)
● Rarely used as a quantitative technique
because of relative difficulty in sample
preparation and complexity of spectra (IR
spectroscopy).
Spectroscopic Techniques
27. Flourescence Spectroscopy/ Fluorometry/
Spectrofluorometry
● Analyzes fluorescence properties of
samples to provide information regarding
their concentration and molecular
environments.
● Uses a beam of light, usually UV/visible
radiation, to excite the electrons in molecules
of certain compounds particularly those with
chromophore and rigid structure, causing them
to emit the radiation at a longer wavelength.
The radiation emitted (emission spectrum)
and/or the radiation absorbed by the sample
(excitation spectrum) can then be measured
and compared with the control.
Uses of Fluorescence Spectroscopy
● Determining the stability of peptide drugs
in solution
● Carrying out limit test where the
impurities are fluorescent or can simply
be rendered fluorescent.
● Determination of fluorescent drugs in low
dose formulations containing non-
fluorescent excipients.
● Studying the binding of drugs to
components in complex formulations
and measuring small amount of drugs
and for studying drug-protein binding in
bioanalysis.
Spectroscopic Techniques
28. Advantages of Fluorescence Spectroscopy
● It is highly sensitive, specific and easy to
carry out.
● Samples are analyzed at low cost as
compared to other analytical techniques.
● It is a selective detection method, thus, it
can be used to quantify a strongly
fluorescent compound in the presence of
a larger amount of non-fluorescent
materials.
● Can be used to monitor changes in
complex molecules e.g., proteins which
are increasingly used as drugs.
Limitations of Fluorescence Spectroscopy
● The technique only applies to a limited
number of molecules as there are
relatively small numbers of compounds
that have characteristic fluorescence.
● The technique is subject to interferences
by UV absorbing species and heavy ions
in solution.
● Fluorescence is affected by temperature.
Spectroscopic Techniques
29. ● It is an analytical technique frequently
used for separating sample mixture into
its individual components. This
technique is based on selective
adsorption of the components on a
stationary phase (usually a solid or liquid
with high surface area).
● As the solute mixture passes over the
stationary phase, the components are
adsorbed and released at the surface at
varying rates depending on differential
affinities of individual components
towards stationary and mobile phase.
● Compared to other available analytical
techniques used in drug-excipient
compatibility studies, chromatography is
known for its characteristics of high
resolution and detection power, making it
suitable for detecting multiple
components in a complex mixture with
high accuracy, precision, specificity, and
sensitivity.
● Various chromatographic methods of
analysis have been used in drug-excipient
compatibility studies.
Chromatographic Techniques
30. Thin Layer Chromatography
● Carried out on glass, plastic or metal
plates coated on one side with a thin
layer of adsorbent (stationary phase) and
is usually made of silica, alumina,
polyamide, cellulose or ion exchange
resin.
● Test samples (i.e., drug – excipient
mixture) and the controls (individual drug
and excipients) are prepared and spotted
on the same baseline at the end of the
plate (the origin). The plate is then placed
upright in a closed chamber containing
mixtures of organic solvents which serve
as the mobile phase. The analyte moves
up the plate, under the influence of the
mobile phase which moves through the
stationary phase by capillary action
(development).
Chromatographic Techniques
31. ● The distance moved by the analyte is
dependent on its relative affinity for the
stationary and the mobile phase.
Incompatibilities are indicated by the
formation of a spot with Rf value
(retardation factor) different from that of
the controls after the plate has been
developed with solvent.
● An excipient on the other hand is
considered to be potentially compatible
with the drug substance if the spots
produced have identical Rf value with
those of the controls.
● Because some samples undergo
negligible thermal changes which might
be difficult to detect by thermal methods
of analysis, TLC is widely used in drug-
excipient compatibility study as a
confirmative test of compatibility after
performing DSC.
Chromatographic Techniques
32. Advantages of Thin Layer Chromatography
● The technique is robust and cheap
● The compound formed as a result of
incompatibilities between the drug and
the excipient can be detected if a suitable
detection reagent is used.
● Unlike GC and HPLC in which some
components of a mixture may elute from
the chromatographic system, there is no
risk of losing any component of the
mixture in TLC since all component of a
mixture can be seen in the
chromatographic system.
● Batch chromatography can be used to
analyze many samples at a time, thus
increasing the speed of analysis.
Limitations of Thin Layer Chromatography
● This technique is not suitable for volatile
substances.
● Sensitivity in often limited.
● Requires more operators skill for optimal
use than HPLC
Chromatographic Techniques
33. High Performance Liquid Chromatography
● Quantitative estimation of test samples
that have been subjected to isothermal
stress testing (IST) is possible.
● Based on mechanisms of adsorption,
partition and ion exchange, depending on
the nature of the stationary phase.
● In HPLC, a liquid mobile phase is pumped
under high pressure through the
stationary phase. A small volume of the
test sample is loaded onto the head
stainless-steel column via a loop valve.
● Separation of a sample mixture occurs
according to the relative lengths of time
spent by its components in the stationary
phase (Rt). Column effluent can be
monitored with a variety of flow-through
device/detector that measures the
amount of the separated components.
● HPLC results that show a percentage
loss similar to the control (drug
considered individually) indicate no
interaction between drug and the
excipients and vice versa.
Chromatographic Techniques
34. Advantages of HPLC
● Suitable for separating nonvolatile or
thermally sensitive molecules such as
amino acids, steroids etc.
● Has broad applicability, that is, it can be
used for both organic and inorganic
samples.
● Can be very sensitive and accurate.
● Provides better precision relative to the
changes being investigated.
● Can be readily automated.
● Less risk of sample degradation since
heating is not required in the process.
Limitations of HPLC
● Takes considerable time and resources
● Solvents used cannot be recycled.
● There is still need for reliable and
inexpensive detectors which can monitor
compounds that lack chromophores.
Chromatographic Techniques
35. ● Drug-excipient compatibility study is a
necessary pre-requisite to the development of
drug products that are safe and stable for use.
● Proper selection and assessment of possible
incompatibilities between the drug and
excipients during preformulatiion studies is of
paramount importance to accomplish the
target product profile and critical quality
attributes.
● To avoid stability problems during drug
development and post-commercialization,
there is need for proper assessment of
possible incompatibilities between the drug
and excipients using appropriate analytical
techniques.
● These analytical techniques are needed not
only to generate useful information with
regards to which excipient is compatible
with a drug substance, but also for
troubleshooting unexpected problems
which might arise during formulation
processes.
● Drug-excipient interactions may take a long
time to be manifested in conventional
stability testing programs, and are not
always predicted by stress and pre-
formulation studies.
Drug-excipient Interactions
36. Thank you
Professor in Pharmaceutics,
Adarsh College of Pharmacy, Vita, Sangli
415311
drkailasmali4u@gmail.com
+91 955 252 7353