The document provides an overview of hot-stage microscopy (HSM), which couples thermal analysis with optical microscopy to observe solid-state materials as a function of temperature and time. HSM is used to support DSC and TGA and detect small changes missed by other techniques, such as desolvation and recrystallization. The instrumentation consists of a computer-controlled hot stage, optical microscope, and camera. HSM has various applications in pharmaceuticals for morphology studies, polymorphism, cocrystal screening, and detecting incompatibilities. It allows visual observation of processes like solid-solid transitions, phase changes, and desolvation.
In this slides contains principle and instrumentation of Differential Scanning Calorimeter (DSC).
Presented by: N Poojitha. (Department of pharmaceutics),
RIPER, anantapur.
In this slides contains principle and instrumentation of Differential Scanning Calorimeter (DSC).
Presented by: N Poojitha. (Department of pharmaceutics),
RIPER, anantapur.
An Infrared spectrum represents a fingerprint of a sample with absorption peaks which correspond to the frequencies of vibrations between the bonds of the atoms making up the material-Because each different material is a unique combination of atoms, no two compounds produce the exact same spectrum, therefore IR can result in a unique identification of every different kind of material!
In this slide contains Interference In Atomic Absorption Spectroscopy and applications.
Presented by: Shaik Gouse ul azam. ( department of pharmaceutical analysis.)
RIPER, anantpur.
a substance can absorb any visible light or external radiation and then again emit it. this called fluorescence and the process of reduction in fluorescence intensity is called quenching. this presentation is all about quenching of fluorescence.
In this slide contains Principle, Methods, Interpretation and applications of XRD.
Presented by: Udit Narayan Singh (Department of pharmaceutics)
RIPER, anantpur.
An Infrared spectrum represents a fingerprint of a sample with absorption peaks which correspond to the frequencies of vibrations between the bonds of the atoms making up the material-Because each different material is a unique combination of atoms, no two compounds produce the exact same spectrum, therefore IR can result in a unique identification of every different kind of material!
In this slide contains Interference In Atomic Absorption Spectroscopy and applications.
Presented by: Shaik Gouse ul azam. ( department of pharmaceutical analysis.)
RIPER, anantpur.
a substance can absorb any visible light or external radiation and then again emit it. this called fluorescence and the process of reduction in fluorescence intensity is called quenching. this presentation is all about quenching of fluorescence.
In this slide contains Principle, Methods, Interpretation and applications of XRD.
Presented by: Udit Narayan Singh (Department of pharmaceutics)
RIPER, anantpur.
Preformulation and physicochemical property of the drugSHIVANEE VYAS
“It is the study of the physical and chemical properties of the
drug prior to compounding process”.
Preformulation commences when a newly synthesized drug shows sufficient pharmacologic promise in animal models towarrant evaluation in man.
These studies should focus on physicochemical properties of new compound that affect drug performance & development of efficaciouss dosage form.
This properties may provide;
A rationale for formulation design
Support the need for molecular modification.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
2. Contents
• Introduction
• Hot-Stage Microscope Instrumentation
• Applications of hot stage microscopy in pharmaceuticals:
1. Morphology studies
2. Amorphous/crystalline form characterization
3. Polymorphism
4. Cocrystal Screening
5. Particle size distribution and characterization of an API in a
tablet
6. Solvates/hydrate screening
7. Miscibility
8. Thermal analysis by surface characterization (TASC)
2
3. Hot stage microscopy (HSM)
• Coupling of thermal analysis with microscopy for the
solid-state characterization of materials as a function of
temperature and time.
• In pharmaceuticals HSM is used to support DSC and
TGA observations and to detect small changes in the
sample that may be missed by DSC and TGA during a
thermal experiment.
• Like Desolvation, recrystallization, phase transitions
and minor changes in the surface.
3
4. Hot-Stage Microscope
• The hot-stage microscope is an optical microscope
equipped with heating and cooling units which allow
observation of a sample under the change of temperature.
• A typical modern hot stage microscope consists of:
1. Computer controlled programmable hot stage
2. Optical microscope for real time observation
3. Polarizing filters
4. Digital camera for recording thermal events
5. Computer and software to control the hot stage and to
carry out the analysis of the thermographs generated
during a thermal event.
4
5. Instrumentation
5
Kumar, A., Singh, P. & Nanda, A. Hot stage microscopy and its applications in pharmaceutical characterization. Appl. Microsc. 50, 12
(2020). https://doi.org/10.1186/s42649-020-00032-9
6. Hot Stage (with glass slide).
Control unit & 2 types of hot stage.
Cont.
6
https://en.donho.com.tw/mettler-toledo-hot-stage-microscopy-
systems.html
7. Cont.
• The sample is heated in a sapphire crucible or glass
slide, either in an open or a closed environment and can
be equipped with a liquid nitrogen unit for rapid
cooling, high pressure pumps or purge gas.
• The temperature of a modern computer controlled hot
stage can be varied from − 200 °C to 600 °C.
7
9. • A part from this basic setup, a hot stage microscope can
be coupled with various other characterization
techniques such as Fourier Transform Infrared
Spectroscopy (FTIR) or Differential scanning Calorimetry
(DSC), high pressure unit or with other non-optical
imaging tools such as scanning electron microscopy
(SEM), and Raman and mass spectroscopy to avail the
simultaneous benefits of both the techniques.
9
10. Applications of Hot Stage Microscopy in
Pharmaceuticals
1-Morphology studies
• Physical features or morphology of a sample under
investigation.
• A wealth of information on how the sample changes when
heated can be obtained by HSM studies.
• Avoiding the misinterpretation of the results obtained from
DSC/TGA and prevents flawed conclusions
10
11. 2- Amorphous/crystalline form
characterization
• The amorphous form of API is preferred in the
pharmaceutical industry due to their higher solubility and
dissolution rates over crystalline forms.
• Amorphous and crystalline forms can be easily
distinguished using a hot stage microscope equipped with
a polarizing filter;
Crystalline materials are known to show birefringence,
while amorphous compounds lack birefringence, hence
can be easily distinguished from crystalline compounds.
11
12. Birefringence
Kumar, A., Singh, P. & Nanda, A. Hot stage microscopy and its applications in pharmaceutical characterization. Appl.
Microsc. 50, 12 (2020). https://doi.org/10.1186/s42649-020-00032-9
12
13. Cont.
• HSM can be useful to study the conversion of an
amorphous API to crystalline form under the effect of
heating.
• To study the effect of storage, especially exposure to heat
and humidity.
• Other than this HSM allows one to observe the
recrystallization process and measure the crystal
growth rate.
13
14. 3- Polymorphism
• Polymorphism is the ability of a substance to exhibit more
than one crystalline structure.
• Different polymorphs of an API may differ in
physicochemical properties and stability.
• It is also possible to study polymorphs which cannot be
grown in a laboratory due to thermodynamic energy
factors, these polymorphs can be grown and studied
thermally on a hot stage.
14
15. “At 175.1 °C the melting of form III was observed in
HSM which was missed by DSC.”
M.R. Bakar, Z.K. Nagy, C.D. Rielly, A combined approach of differential scanning calorimetry and hot-stage microscopy with image analysis in the
investigation of sulfathiazole polymorphism. J. Therm. Anal. Calorim. 99(2), 609–619 (2010). https://doi.org/10.1007/s10973-009-0001-z
15
16. M.R. Bakar, Z.K. Nagy, C.D. Rielly, A combined approach of differential scanning calorimetry and hot-stage microscopy with image
analysis in the investigation of sulfathiazole polymorphism. J. Therm. Anal. Calorim. 99(2), 609–619 (2010).
https://doi.org/10.1007/s10973-009-0001-z
16
17. 4- Cocrystal Screening
• Cocrystals are multicomponent solid forms consisting two
or more different molecules non covalently bonded to
each other in same the crystal lattice.
• Cocrystals have recently gained a lot of attention in
academia due to their ability to modulate
physicochemical properties of an API.
• Screening through HSM is rapid, solvent free and
requires small quantities of API and coformer.
• Kofler contact method (also known as Kofler mixed
fusion)
17
18. Kavanagh ON, Croker DM, Walker GM, Zaworotko MJ. Pharmaceutical cocrystals: from serendipity to design to application. Drug Discov Today. 2019 Mar;24(3):796-804. doi:
10.1016/j.drudis.2018.11.023. Epub 2018 Dec 3. PMID: 30521935.
18
20. Cocrystal Screening ofAPI with GlutaricAcid cont.
D.P. McNamara, S.L. Childs, J. Giordano, A. Iarriccio, J. Cassidy, M.S. Shet, R. Mannion, E. O'Donnell, A. Park, Use of a glutaric acid
cocrystal to improve oral bioavailability of a low solubility API. Pharm. Res. 23(8), 1888–1897 (2006). https://doi.org/10.1007/s11095-006-
9032-3
-Glutaric acid was chosen as the potential coformer based on melt experiments
because of its good aqueous solubility, stability and melting point.
20
21. 5- Particle size distribution and characterization
of an API in a tablet
• Particle size distribution has a profound effect on the
processability of raw and finished products, which in turn
effects the dissolution, bioavailability, stability profile
and thus ensures the quality, safety and efficacy of the
finished formulation.
• Although there are methods to determine the particle size
of API in a tablet but they have their own limitations such
as the inability to differentiate between agglomerates
of the tablet constituents.
21
25. 6- Solvates/hydrate screening
• Solvates are formed when solvent molecules get
incorporated in the host compound structure. When water
gets incorporated in the host compound, these type of
solvates are called hydrates.
• Hot stage microscopy can also be used for
solvate/hydrate screening since it allows the visual
observation of the gas evolved during the desolvation
of the sample under heat.
25
26. A. Jacobs, F.M. Noa, Hybrid salt–cocrystal solvate: P-coumaric acid and quinine system. J. Chem. Crystallogr. 44(2), 57–62 (2014). https://doi.org/10.1007/
26
27. 7- Pharmaceutical Incompatibility and Miscibility
• DSC has been successfully used for detection of compatibility
in the binary mixture of the drug and excipient.
• HSM has proven to be advantageous as the interactions can
be visually observed which was limited in DSC studies.
Hence HSM can be used to supplement the data obtained
from DSC to detect possible compatibility or incompatibility.
• Thus, HSM can serve as a rapid, green and cheaper
approach for detecting pharmaceutical incompatibilities and
to observe the miscibility of API and excipients into one another
which can find application in the screening of excipients
compatible with the API and polymers for preparation of solid
dispersions.
27
28. Miscibility Study
• They screened lacidipine with 11 excipients of polymeric
and non-polymeric nature.
• The miscible components formed an amorphous solid
solution whereas the immiscible components resulted in
amorphous drug dispersed in crystalline.
A. Forster, J. Hempenstall, I. Tucker, T. Rades, Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and
thermal analysis. Int. J. Pharm. 226(1–2), 147–161 (2001). https://doi.org/10.1016/S0378-5173(01)00801-8
28
29. M. Alhijjaj, M. Reading, P. Belton, S. Qi, Thermal analysis by structural characterization as a method for assessing heterogeneity in complex solid pharmaceutical dosage forms. Anal. Chem.
87(21), 10848–10855 (2015).
8-Thermal analysis by surface characterization (TASC)
29
30. M. Reading, Thermal analysis by structural characterization (TASC): Structural and thermo-rheological information from hot stage microscopy. Microscopy
Today 25(5), 18–23 (2017). https://doi.org/10.1017/S1551929517000815
30
31. References:
• Kumar, A., Singh, P. & Nanda, A. Hot stage microscopy and its applications in pharmaceutical characterization. Appl.
Microsc. 50, 12 (2020). https://doi.org/10.1186/s42649-020-00032-9
• M.R. Bakar, Z.K. Nagy, C.D. Rielly, A combined approach of differential scanning calorimetry and hot-stage microscopy with
image analysis in the investigation of sulfathiazole polymorphism. J. Therm. Anal. Calorim. 99(2), 609–619 (2010).
https://doi.org/10.1007/s10973-009-0001-z
• M.R. Bakar, Z.K. Nagy, C.D. Rielly, A combined approach of differential scanning calorimetry and hot-stage microscopy with
image analysis in the investigation of sulfathiazole polymorphism. J. Therm. Anal. Calorim. 99(2), 609–619 (2010).
https://doi.org/10.1007/s10973-009-0001-z
• Kavanagh ON, Croker DM, Walker GM, Zaworotko MJ. Pharmaceutical cocrystals: from serendipity to design to application.
Drug Discov Today. 2019 Mar;24(3):796-804. doi: 10.1016/j.drudis.2018.11.023. Epub 2018 Dec 3. PMID: 30521935.
• D.P. McNamara, S.L. Childs, J. Giordano, A. Iarriccio, J. Cassidy, M.S. Shet, R. Mannion, E. O'Donnell, A. Park, Use of a
glutaric acid cocrystal to improve oral bioavailability of a low solubility API. Pharm. Res. 23(8), 1888–1897 (2006).
https://doi.org/10.1007/s11095-006-9032-3
• A. Jacobs, F.M. Noa, Hybrid salt–cocrystal solvate: P-coumaric acid and quinine system. J. Chem. Crystallogr. 44(2), 57–62
(2014). https://doi.org/10.1007/
• A. Forster, J. Hempenstall, I. Tucker, T. Rades, Selection of excipients for melt extrusion with two poorly water-soluble drugs by
solubility parameter calculation and thermal analysis. Int. J. Pharm. 226(1–2), 147–161 (2001). https://doi.org/10.1016/S0378-
5173(01)00801-8
• M. Alhijjaj, M. Reading, P. Belton, S. Qi, Thermal analysis by structural characterization as a method for assessing
heterogeneity in complex solid pharmaceutical dosage forms. Anal. Chem. 87(21), 10848–10855 (2015).
• M. Reading, Thermal analysis by structural characterization (TASC): Structural and thermo-rheological information from hot
stage microscopy. Microscopy Today 25(5), 18–23 (2017). https://doi.org/10.1017/S1551929517000815
31