Solid Sample Differential Scanning Calorimetry in Biopharmacutical Discovery and Development

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
Bhusnure World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 5.210
Volume 5, Issue 1, 440-454 Review Article ISSN 2278 – 4357
SOLID SAMPLE DIFFERENTIAL SCANNING CALORIMETRY IN

BIOPHARMACUTICAL DISCOVERY AND DEVELOPMENT
Dr. Bhusnure O.G*

M. Pharm, Ph.D.Professor and Head, Department Of Quality Assurance, Channabasweshwar
Pharmacy College, Kava Road, Latur-413512, Dist. Latur. (MS)
ABSTRACT
Article Received on
10 Nov. 2015, Differential Scanning Calorimetry (DSC) is a highly sensitive
Revised on 01 Dec. 2015, technique to study the thermotropic properties of many different
Accepted on 22 Dec. 2015,
biological macromolecules and extracts. Since its early development,
DSC has been applied to the pharmaceutical field with excipient
*Correspondence for studies and DNA drugs. In recent times, more attention has been
Author applied to lipid-based drug delivery systems and drug interactions with
Dr. Bhusnure O.G
biomimetic membranes. Highly reproducible phase transitions have
Professor and Head,
been used to determine values, such as, the type of binding interaction,
Department Of Quality
Assurance, purity, stability, and release from a drug delivery mechanism. This
Channabasweshwar review focuses on the use of DSC for biochemical and pharmaceutical
Pharmacy College, Kava applications.
Road, Latur-413512, Dist.
Latur. (MS) KEYWORDS: Differential scanning calorimetry, drug,
macromolecule, lipid, antimicrobial peptide, drug development,
pharmaceutical, drug characterization, nanoparticles
INTRODUCTION
Differential Scanning Calorimetry (DSC), is a straight forward, non-perturbing technique,
first developed in the early1960s. This method measures the thermodynamic properties of
thermally induced transitions and has been applied to a variety of biological macromolecules
such as lipids or proteins.[1,2] Examples of these applications have involved conformational
states of proteins, DNA binding to protein, [3] biopolymer melting, lipid phase transitions, and
lipid-protein interactions.[1,4]
Differential Scanning Calorimetry is primarily used to determine the energetics of phase

transitions and conformational changes and allows quantification of their temperature
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dependence.[5] Technical improvements over time have resulted in high sensitivity

instruments, which also make DSC a very relevant tool for investigating the thermodynamic
properties of various pharmaceutical products, such as, biopolymers, proteins, peptides, and
lipid carriers.[1,4]
Many reviews are available on protein conformation, [4] biopolymers stabilization,[6]

thermodynamic properties of lipids,[1] and lipid-protein interactions,[7] however, this article
will focus on the application of DSC in the pharmaceutical field, with an emphasis on drug-
lipid interactions. Many groups have made relevant contributions and no overview can be
fully comprehensive to acknowledge that. Most references in this article are reviews that will
provide the reader with sources for a wealth of detailed references.
Physical characterization of pharmaceuticals remains an important tool for the

pharmaceutical chemist in R&D, formulation, and QA/QC. Information about the purity of a
material, its polymorphic composition, the presence of excipients, the amount of amorphous
material present, and the glass transition of lyophilized materials are all obtained via thermal
methods like Differential Scanning Calorimetry (DSC). Because of this, a DSC is a familiar
tool in most pharmaceutical laboratories. However, many users are still aware of the
increases in sensitivity and other advantages of Fast Scanning Rate DSC techniques. Fast
Scanning Rate DSC, better known under its trade name from PerkinElmer® as Hyper
DSCTM, is a technique in which the sample is heated or cooled at rates of 200Â°C or greater
per minute over the same temperature range as is used in Conventional DSC. Fast Scanning
Rate DSC exploits the standard heat flow equations to increase the sensitivity of the
instrument by using increased heating rates (Figure 1). Because of the design of power
compensation, DSC, with its very small furnace mass, rates of up to 750Â°C/min can be
obtained for quantitative data. This makes Fast Scanning rate DSC very sensitive to the
presence of amorphous material in a sample. In addition, high throughput can be achieved as
runs typically take less than 1 to 3 minutes. This greatly increases the number of samples one
can run in a day. For example, an autosampler system running samples at 200Â°C/min allows
up to 268 runs to be done in 24 hours.
Thermal Analysis
 Definition
The term thermal analysis (TA) is frequently used to describe analytical experimental
techniques which investigate the behavior of a sample as a function of temperature.

TA refers to conventional TA techniques such as differential scanning calorimetry (DSC),

differential thermal analysis (DTA), thermogravimetry (TG), thermo mechanical analysis
TMA) and dynamic mechanical analysis (DMA). A selection of representative TA curves is
presented in Figure 1.1.
Type of thermal analysis

1. Thermogrvimetry
2. Differential Scanning Calorimetry
3. Dilatometry thermomechanical analysis
4. Dynamic mechanical analysis
Characteristics of Thermal Analysis

The advantages of TA over other analytical methods can be summarized as follows
(i) The sample can be studied over a wide temperature range using various temperature
programmes.
(ii) Almost any physical form of sample (solid, liquid or gel) can be accommodated using a
variety of sample vessels or attachments.
(iii) A small amount of sample (0.1 μg-10 mg) is required.
(iv) The atmosphere in the vicinity of the sample can be standardized.
(v) The time required to complete an experiment ranges from several minutes to several
hours.
(vi) TA instruments are reasonably priced. In polymer science, preliminary investigation of
the sample transition temperatures and decomposition characteristics is routinely
performed using TA before spectroscopic analysis is begun.

Differential Scanning Calorimetry

Principle
A calorimeter, measures the heat into or out of a sample. A differential calorimeter,
measures the heat of sample relative to a reference. A differential scanning calorimeter,
does all of the above and heats the sample with a linear temperature ramp. Endothermic heat
flows into the sample. Exothermic heat flows out of the sample. Differential Scanning
Calorimetry (DSC), measures the temperatures and heat flows associated with transitions in
materials as a function of time and temperature in a controlled atmosphere. These
measurements provide quantitative and qualitative information about physical and chemical
changes that involve endothermic or exothermic processes or changes in heat capacity.
Differential scanning calorimetry (DSC) monitors heat effects associated with phase
transitions and chemical reactions as a function of temperature. In a DSC the difference in
heat flow to the sample and a reference at the same temperature, is recorded as a function of
temperature. The reference is an inert material such as alumina, or just an empty aluminum
pan. The temperature of both the sample and reference are increased at a constant rate.
Differential Scanning Calorimeter (DSC) is a powerful and versatile thermal analyzer that
allows for property measurements on a broad variety of materials from -150 to 600°C. The
DSC determines the temperature and heat flow associated with material transitions as a
function of time and temperature. It also provides quantitative and qualitative data on
endothermic (heat absorption) and exothermic (heat evolution) processes of materials during
physical transitions that are caused by phase changes, melting, glass transitions,
crystallization, oxidation, and other heat related changes. This information helps the scientist
or engineer identify processing and end-use performance. The DSC instrument works in
conjunction with a controller and associated software to allow for data acquisition and
analysis.
Theory
 Heat
Energy transfer between two bodies due to thermal communication
 Calorimetry
Measuring the heat of physical/chemical interactions

 Heat capacity
The amount of heat needed to increase temperature of a substance
The integral under the DSC peak, above the baseline, gives the total enthalpy change for the
process
Assuming that the heat capacity of the reference is constant over the temperature range
covered by the peak, ΔHreference will cancel out because the integral above the baseline is
taken. Therefore, equation 2 is also valid when the integral is taken from the DCS plot of
ΔdH/dt. Heat capacities and changes in heat capacity can be determined from the shift in the
baseline of the thermogram. The heat capacity is defined as
The temperature scan rate is
Using the chain rule

Where dH/dt is the shift in the baseline of the thermogram (Figure 3-4) and the last derivative
is just the inverse of the scan rate. For differential measurements, we determine the difference
in the heat capacity of the sample and the reference
INSTRUMENTATION
Differential scanning calorimetry (DSC) is a technique for measuring the energy necessary to
establish a nearly zero temperature difference between a substance and an inert reference
material, as the two specimens are subjected to identical temperature regimes in an
environment heated or cooled at a controlled rate.
1. Power-compensated DSC
1. Separate heating of sample and reference
2. Identical temperature difference
3. Measurement of electrical power
2. Heat flux DSC

1. In-concert heating of sample and reference
2. Measurement of temperature change
Power-compensation DSC: the specimen (TS) and reference (TR) temperatures are
controlled independently using separate (identical) ovens. The temperature difference
between the sample and reference is maintained to zero by varying the power input to the two
furnaces. This energy is then a measure of the enthalpy or heat capacity changes in the test
specimen S (relative to the reference R).
-The tempreture of the sample and reference are equal to each other. Both tempreture are
increased or decreased linearly.
-Two independent heating units are employed.
Thease heating units are quite small, allowing for rapid rate of heating, cooling and
equilibration.
-The heating units embedded in a large tempreture controlled heat sink.

-The holder have platinum resistance thermometers to monitor the tempreture of the material.
-The instrument records the power difference needed to maintain the sample and reference at
the same tempreture.
As function of the programmed tempreture.
-Power it has lower sensitivity than heat-flux Dsc. But it response time is more rapid.
-This make well suitable for kinetics studies (In fast equilibration to new tempreture setting.)
-It is also capable of higher resolution than heat-flux Dsc.
Heat-flux DSC: the test specimen S and reference material R (usually an empty sample
pan+lid) are enclosed in the same furnace together with a metallic block with high thermal
conductivity that ensures a good heat-flow path between S and R. The enthalpy or heat
capacity changes in the specimen S lead to temperature differences relative to R. This results
in a certain heat-flow between S and R, however small compared to those in DTA, because of
the good thermal contact between S and R. The temperature difference DT between S and R
is recorded and further related to the enthalpy change in the specimen using calibration
experiments. The heat-flux DSC system is thus a slightly-modified DTA system: the only
important difference is the good heat-flow path between the specimen and reference
crucibles.
The DSC instrument used in the present experiment is a heat-flux type NETZSCH 404C
Pegasus calorimeter. Therefore special attention will be given to this type of instruments.

 Purge Gas
When operating above ambient temperature, N2 gas is the most commonly employed purge
gas. A number of grades of N2 are available. Standard N2 gas has a purity of 99.99%, where
water vapour and oxygen are the principal impurities. This grade of N2 should be dried, by
passing it through a drying column containing silica gel, before the gas purges the instrument
sample holder assembly. Three other grades, denoted, A, B and S, are available with purities
of 99.9998, 99.9995 and 99.9999%, respectively. Air is not used as a purge gas because of its
complex composition and high water vapour content. The nature of the purge gas has an
important influence on the shape of the DSC peak, particularly for the decomposition
reactions observed in simultaneous TG-DTA.
A number of inert purge gases are used when operating at sub-ambient temperatures. The
choice of purge gas is largely determined by the proposed experimental parameters. Table 4.1
lists the thermal conductivities of the most commonly used sub-ambient purge gases (Ar, He
and N2 ) as a function of temperature and pressure. If the purge gas is changed the
temperature and energy scales of the instrument must be recalibrated. In some apparatuses the
sample holder assembly is housed in a dry box through which N2 is purged.
The gas flow rate influences the characteristics of the instrument baseline. When the flow rate
is too high the instrument baseline becomes unstable. Fluctuations in the flow rate alter the
baseline gradient.

A purge gas flow rate in the range 20-50 ml/min is recommended. Measurements under
reduced pressure are generally only performed with simultaneous TG-DTA instruments and
are discussed in Section 4.5.
 Sample Packing
Sample packing has an important influence of the characteristics of DSC curves. The sample
must be in good thermal contact with the sample vessel to optimize the heat flow between the
heat source and the sample, reducing thermal lag. The sample should be packed to minimize
the number of voids between sample particles, because the thermal conductivity of air is
generally very low compared with the sample. This is particularly important when measuring
fibres or fabrics. If the sample shape is not regular, the sample may become deformed during
heating, increasing the noise level on the sample baseline.
The sample packing should be reproducible and as uniform as possible. Various packing
schemes are illustrated in Figure 3.10, for open-type and hermetically sealed-type DSC
sample vessels. Samples I and IV are correctly packed. All of the other packing schemes will
give rise to artifacts in the DSC curve. Figure 3.11 shows the melting peak temperature of
polyoxymethylene, in the form of whisker-type extended-chain crystals, as a function of
heating rate, for a densely packed and a loosely packed sample. The temperature of melting is
dependent on the packing scheme over the entire range of heating rates.
APPLICATION
1. Phase Transitions
Every solid state material when continuously heated will come to a point where it changes
phase. For example ice, when heated, at standard atmospheric pressure, will undergo a phase
change from solid to liquid (melt) at a transition temperature (melting point) of 0 oC, and

when the resulting water is heated, it will eventually undergo another phase transition from
liquid to gas (vaporize) at a transition temperature (boiling point) of 100 oC.
The energy supplied simply goes into converting the solid to liquid, that is, the energy is
spent in breaking down the rigid solid structure into the much less rigid liquidstate, leading to
gain in energy of the material (an endothermic transition).
2. Glass Transitions
Glass transitions can only take place in an amorphous material. A glass transition has no
latent heat associated with it, and such transitions are referred to as second order transitions.
The heat flow vs. temperature for a glass transition is as shown in Figure 3.
In this case, the heat capacity has increased and the molecules have become more mobile, and
so the material is now in a state where its atoms/molecules have more energy. In order to
keep the heat rate constant, the sample pan heater needed to increase heat flow. The material
is still amorphous but has undergone a transition from a lower energy state to a higher energy
state.
The temperature at which the material undergoes a glass transition is known as the glass
transition temperature (TG), and as seen in Figure 3,
Figure 3. Glass transition temperature (TG) of Silicon Rubber.
Glass transitions may occur as the temperature of an amorphous solid is increased. These
transitions appear as a step in the baseline of the recorded DSC signal. This is due to the
sample undergoing a change in heat capacity; no formal phase change occurs.

As the temperature increases, an amorphous solid will become less viscous. At some point
the molecules may obtain enough freedom of motion to spontaneously arrange themselves
into a crystalline form. This is known as the crystallization temperature (Tc). This transition
from amorphous solid to crystalline solid is an exothermic process, and results in a peak in
the DSC signal. As the temperature increases the sample eventually reaches its melting
temperature (Tm). The melting process results in an endothermic peak in the DSC curve. The
ability to determine transition temperatures and enthalpies makes DSC a valuable tool in
producing phase diagrams for various chemical systems.
3. Crystallization: When a material is crystallized, it becomes ordered. Crystallization is a

first order transition, and thus a latent heat is associated with the transition. As shown in
Figure 2, the process is exothermic, that is, thermal energy is released and the sample gets
hotter, and so during crystallization, the sample heater supplies less energy than the reference
heater to maintain the constant set heat rate. As can be seen from the shape of the
crystallization profile in Figure 2, it takes a while for all the material to go from the
amorphous state to the crystalline state, and so the presence of mixed phases during the
crystallization process. The shape is also affected by constraints of current technology.
The crystallization temperature (Tc) is at the peak of the depression in the graph. The area of
the depression can be obtained and using the heating rate and the mass of the sample, the
latent heat of crystallization may be calculated. At or near the crystallization temperature,
thematerial has gained enough energy so that its atoms/molecules could re-arrange into a
more stable and ordered state. By nature, materials tend toward the lowest energy state, and
the lowest energy state possible is one of order. A crystalline material can undergo solid-solid
phase transitions.
For example Cesium Nitrate, undergoes a solid-solid phase transition at 154 oC
4. Melting
When amaterialmelts, it becomes disordered in the form of a liquid. In materials that are
made up of either several different phases or different components, A dsc may showmultiple
melting transitions. There are various theories as to what causes a material to melt and what
is actually happening on the molecular level as it melts. General observations about melting
include three major components. The first is that melting always occurs with an increase in
disorder. Second, there is always a change in volume (positive or negative). Third, there is

always a change in heat capacity. A simple theory of melting backed by experiments, is that
of Lindemann (1910)
As the temperature increases, the vibrational amplitudes increase, finally reaching a critical
fraction of the lattice distance that renders the crystal unstable. A material cannot melt unless
it is a crystal. Therefore, any material that melts must first crystallize.
An example of the heat flow vs. temperature graph during melting can be seen in Figures 1
and 2, showing melting as an endothermic process.
Examples
The technique is widely used across a range of applications, both as a routine quality test and
as a research tool. The equipment is easy to calibrate, using low melting indium at 156.5985
°C for example, and is a rapid and reliable method of thermal analysis.
Polymers
DSC is used widely for examining polymeric materials to determine their thermal transitions.
The observed thermal transitions can be utilized to compare materials, although the
transitions do not uniquely identify composition. The composition of unknown materials may
be completed using complementary techniques such as IR spectroscopy. Melting points and
glass transition temperatures for most polymers are available from standard compilations, and
the method can show polymer degradation by the lowering of the expected melting point, Tm,
for example. Tm depends on the molecular weight of the polymer and thermal history, so
lower grades may have lower melting points than expected. The percent crystalline content of
a polymer can be estimated from the crystallization/melting peaks of the DSC graph as
reference heats of fusion can be found in the literature. DSC can also be used to study thermal
degradation of polymers using an approach such as Oxidative Onset Temperature/Time
(OOT), however, the user risks contamination of the DSC cell, which can be problematic.
Thermogravimetric Analysis (TGA) may be more useful for decomposition behavior
determination. Impurities in polymers can be determined by examining thermograms for
anomalous peaks, and plasticisers can be detected at their characteristic boiling points. In
addition, examination of minor events in first heat thermal analysis data can be useful as
these apparently "anomalous peaks" can in fact also be representative of process or storage
thermal history of the material or polymer physical aging. Comparison of first and second

heat data collected at consistent heating rates can allow the analyst to learn about both
polymer processing history and material properties.
Liquid crystals
DSC is used in the study of liquid crystals. As some forms of matter go from solid to liquid
they go through a third state, which displays properties of both phases. This anisotropic liquid
is known as a liquid crystalline or mesomorphous state. Using DSC, it is possible to observe
the small energy changes that occur as matter transitions from a solid to a liquid crystal and
from a liquid crystal to an isotropic liquid.
Oxidative stability
Using differential scanning calorimetry to study the stability to oxidation of samples
generally requires an airtight sample chamber. Usually, such tests are done isothermally (at
constant temperature) by changing the atmosphere of the sample. First, the sample is brought
to the desired test temperature under an inert atmosphere, usually nitrogen. Then, oxygen is
added to the system. Any oxidation that occurs is observed as a deviation in the baseline.
Such analysis can be used to determine the stability and optimum storage conditions for a
material or compound.
Safety Screening
DSC makes a reasonable initial safety screening tool. In this mode the sample will be housed
in a non-reactive crucible (often gold, or gold plated steel), and which will be able to
withstand pressure (typically up to 100 bar). The presence of an exothermic event can then be
used to assess the stability of a substance to heat. However, due to a combination of relatively
poor sensitivity, slower than normal scan rates (typically 2-3 °/min - due to much heavier
crucible) and unknown activation energy, it is necessary to deduct about 75-100 °C from the
initial start of the observed exothermic to suggest a maximum temperature for the material. A
much more accurate data set can be obtained from an adiabatic calorimeter, but such a test
may take 2–3 days from ambient at a rate of a 3 °C increment per half hour.
Drug analysis
DSC is widely used in the pharmaceutical and polymer industries. For the polymer chemist,
DSC is a handy tool for studying curing processes, which allows the fine tuning of polymer
properties. The cross-linking of polymer molecules that occurs in the curing process is
exothermic, resulting in a positive peak in the DSC curve that usually appears soon after the

glass transition. In the pharmaceutical industry it is necessary to have well-characterized drug

compounds in order to define processing parameters. For instance, if it is necessary to deliver
a drug in the amorphous form, it is desirable to process the drug at temperatures below those
at which crystallization can occur.
General chemical analysis

Freezing-point depression can be used as a purity analysis tool when analysed by differential
scanning calorimetry. This is possible because the temperature range over which a mixture of
compounds melts is dependent on their relative amounts. Consequently, less pure compounds
will exhibit a broadened melting peak that begins at lower temperature than a pure
compound.
CONCLUSION
Differential scanning calorimetry (DSC) is frequently the pharmaceutical thermal analysis
technique of choice because of its ability to provide detailed information about both the
physical and energetic properties of a substance. This review provides an up-to-date overview
of the applications of DSC in the drug development process. It should serve as a broad
introduction to those starting work in this area, and also as a valuable reference for those
already practising in this field. Fast Scanning DSC can be applied to a wide range of
thermophysical measurements used in the modern pharmaceutical laboratory. Because it
allows faster throughput and smaller sample sizes, it can reduce testing costs and increase
efficiency. The ability to "freeze" kinetic changes in a sample mean that we can, for the first
time, be sure what we see in the DSC is what was originally present in the sample and not the
product of thermally induced changes. With the great increase in sensitivity of Fast Scanning
Rate DSC, materials can now be detected that were previously below the detection limits of
DSC.
REFERENCE
1. McElhaney RN. The use of differential scanning calorimetry and differential thermal
analysis in studies of model and biological membranes. Chem Phys Lipids. 1982; 30:
229–59. [PubMed]
2. Freire E. Differential scanning calorimetry. Methods Mol Biol. 1995;40:191–
218. [PubMed]
3. Privalov PL, Dragan AI. Microcalorimetry of biological macromolecules. Biophys
Chem. 2007; 126: 16–24. [PubMed]

4. Sturtevant J. Biochemical applications of differential scanning calorimetry. Ann Rev Phys

Chem. 1987; 38: 463–88.
5. Jelesarov I, Bosshard HR. Isothermal titration calorimetry and differential scanning
calorimetry as complementary tools to investigate the energies of biomolecular
recognition. J Mol Recognit. 1999; 12: 3–18.[PubMed]
6. Shnyrov VL, Sanchez-Ruiz JM, Boiko BN, Zhadan GG, Permyakov EA. Applications of
scanning microcalorimetry in biophysics and biochemistry. Thermochim Acta. 1997; 302:
165–80.
7. McElhaney RN. Differential scanning calorimetric studies of lipid-protein interactions in
model membrane systems. Biochim Biophys Acta. 1986; 864: 361–421. [PubMed]
8. M. I. Pope and M.J. Judd: "Differential Thermal Analysis", London, Heyden, Academic
Press 1977.
9. J. Sestak, V. Satava and W.W. Wendlandt: Thermochimica Acta, 1973; 7: 333.
10. V. Konryushin and L.N. Larikov: J. Mat. Sci., 1978; 13(1).
11. A. L. Greer: Thermochimica Acta, 1980; 42: 193.
12. R. A. Baxter:`Thermal Analysis', 1, 65 (1969) - eds. R.F. Sswenker and P.D. Garn,
Academic Press.
13. H. K. Yuen, C.J. Yosel: Thermochimica Acta, 1979; 33: 281.
14. L. M. Clareborough, M. E. Hargreaves, D. Mitchell and G. West: Proc. Roy. Soc., A215,
1952; 507.
15. M. G. Scott and P. Ramachandrarao: Mat. Sci. & Eng., 1977; 29: 137.
16. M. G. Scott: J. Mat. Sci., 13, 291 (1978). Kinetics of glass crystallisation. Anal. Chem.,
1957; 29: 1702.
17. Sandler, S.R., Karo, W., (1998). Polymer Synthesis and Characterization, Academic
Press.

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WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Bhusnure World Journal of Pharmacy and Pharmaceutical Sciences

Volume 5, Issue 1, 440-454 Review Article ISSN 2278 – 4357

SOLID SAMPLE DIFFERENTIAL SCANNING CALORIMETRY IN

Dr. Bhusnure O.G*

Differential Scanning Calorimetry is primarily used to determine the energetics of phase

www.wjpps.com Vol 5, Issue 1, 2016. 440

dependence.[5] Technical improvements over time have resulted in high sensitivity

Many reviews are available on protein conformation, [4] biopolymers stabilization,[6]

Physical characterization of pharmaceuticals remains an important tool for the

www.wjpps.com Vol 5, Issue 1, 2016. 441

TA refers to conventional TA techniques such as differential scanning calorimetry (DSC),

Type of thermal analysis

Characteristics of Thermal Analysis

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Differential Scanning Calorimetry

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The temperature scan rate is

Using the chain rule

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2. Heat flux DSC

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As function of the programmed tempreture.

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Figure 3. Glass transition temperature (TG) of Silicon Rubber.

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3. Crystallization: When a material is crystallized, it becomes ordered. Crystallization is a

For example Cesium Nitrate, undergoes a solid-solid phase transition at 154 oC

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glass transition. In the pharmaceutical industry it is necessary to have well-characterized drug

General chemical analysis

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4. Sturtevant J. Biochemical applications of differential scanning calorimetry. Ann Rev Phys

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