1. The document discusses methods for determining pKa (acid dissociation constant) and log P (partition coefficient) of compounds. Common methods for pKa include potentiometric titration, spectrophotometry, and NMR titration. Methods for measuring log P include shake flask experiments and HPLC.
2. The document then gives an example procedure for determining the pKa of aspirin via titration with sodium hydroxide solution.
3. Factors that influence choice of solvents for measuring log P are discussed. Octanol is commonly used to model membrane permeability. The document lists typical log P values for some compounds and their applications in pharmacology.
Introduction
working principle
fragmentation process
general rules for fragmentation
general modes of fragmentation
metastable ions
isotopic peaks
applications
Introduction
working principle
fragmentation process
general rules for fragmentation
general modes of fragmentation
metastable ions
isotopic peaks
applications
Liquid liquid extraction useful for B. Pharmacy students. solvent extraction is one of the separation technique and it is the most common method adopted in the field of analysis
ION EXCHANGE CHROMATOGRAPHY
ByM.Vharshini
B.Sc. Bio Medical Science
Sri Ramachandra University
ION EXCHANGE CHROMATOGRAPHY
Ion-exchange chromatography is a process that allows the separation of ions and polar molecules based on their affinity to the ion exchanger.
It can be used for almost any kind of charged molecule including large proteins, small nucleotides and amino acids.
Cations or Anions can be separated using this method.
PRINCIPLE
It is based on the reversible electrostatic interaction of ions with the separation matrix (i.e.)
The separation occurs by reversible exchange of ions between the ions present in the solution and those present in the ion exchange resin.
CLASSIFICATION OF RESINS
According to the chemical nature they classified as-
1. Strong cation exchange resin
2. Weak cation exchange resin
3. Strong anion exchange resin
4. Weak anion exchange resin
According to the Source they can -
Natural resins : Cation - Zeolytes, Clay
Anion - Dolomite
Synthetic resins: Inorganic & Organic resins
◘Organic resins are polymeric resin matrix.
The resin composed of –
Polystyrene (sites for exchangeable functional groups)
Divinyl benzene(Cross linking agent)-offers stability.
Ion exchange resin should have following requirements
»It must be chemically stable.
»It should be insoluble in common solvents.
» It should have a sufficient degree of cross linking.
»The swollen resin must be denser than water.
»It must contain sufficient no. of ion exchange groups.
Physical properties of ion exchange resins
Cross linking:
It affects swelling & strength & solubility
Swelling:
When resin swells, polymer chain spreads apart
Polar solvents → swelling
Non-polar solvents → contraction
Swelling also affected electrolyte concentration.
Particle size and porosity
Increase in surface area & decrease in particle size will increase the rate of ion exchange.
Regeneration
Cation exchange resin are regenerated by treatment with acid, then washing with water.
Anion exchange resin are regenerated by treatment with NaOH, then washing with water until neutral.
EXPERIMENTAL SETUP OF ION EXCHANGE CHROMATOGRAPHY
Metrohm 850 Ion chromatography system
Instrumentation of ion exchange chromatography
PRACTICAL REQUIREMENTS
1.Column
» glass, stainless steel or polymers
2.Packing the column
» Wet packing method:
A slurry is prepared of the eluent with the stationary phase powder and then carefully poured into the column. Care must be taken to avoid air bubbles.
3.Application of the sample
After packing, sample is added to the top of the stationary phase, use syringe or pipette.
This layer is usually topped with a small layer of sand or with cotton or glass wool to protect the shape of the organic layer from the velocity of newly added eluent.
4.Mobile phase
Acids, alkalis, buffers…
6.Stationary phase
The ionic
The movement of molecules from one phase to another is called partitioning.
If two immiscible phases are placed adjacent to each other, the solute will distribute itself between two immiscible phases until equilibrium is attained; therefore no further transfer of solute occurs.
A presentation on column efficiency parameters in chromatography.. A part of gas chromatography in pharmacutical analysis..will be helpful for all mphrm students
Optical Rotation and Polarimeter by Dr. A. AmsavelDr. Amsavel A
Isomers and enantiomers
Specific Optical Rotation
Polarimeter
Instrumentation and Operation
Factors affect the Optical Rotation
Calibration
Application Specifically Pharmaceutical Industries
Quadrupole and Time of Flight Mass analysers.Gagangowda58
Description about important mass analysers Quadrupole and TOF: Principle, Construction and Working, Advantages and Disadvantages and their Applications.
Liquid liquid extraction useful for B. Pharmacy students. solvent extraction is one of the separation technique and it is the most common method adopted in the field of analysis
ION EXCHANGE CHROMATOGRAPHY
ByM.Vharshini
B.Sc. Bio Medical Science
Sri Ramachandra University
ION EXCHANGE CHROMATOGRAPHY
Ion-exchange chromatography is a process that allows the separation of ions and polar molecules based on their affinity to the ion exchanger.
It can be used for almost any kind of charged molecule including large proteins, small nucleotides and amino acids.
Cations or Anions can be separated using this method.
PRINCIPLE
It is based on the reversible electrostatic interaction of ions with the separation matrix (i.e.)
The separation occurs by reversible exchange of ions between the ions present in the solution and those present in the ion exchange resin.
CLASSIFICATION OF RESINS
According to the chemical nature they classified as-
1. Strong cation exchange resin
2. Weak cation exchange resin
3. Strong anion exchange resin
4. Weak anion exchange resin
According to the Source they can -
Natural resins : Cation - Zeolytes, Clay
Anion - Dolomite
Synthetic resins: Inorganic & Organic resins
◘Organic resins are polymeric resin matrix.
The resin composed of –
Polystyrene (sites for exchangeable functional groups)
Divinyl benzene(Cross linking agent)-offers stability.
Ion exchange resin should have following requirements
»It must be chemically stable.
»It should be insoluble in common solvents.
» It should have a sufficient degree of cross linking.
»The swollen resin must be denser than water.
»It must contain sufficient no. of ion exchange groups.
Physical properties of ion exchange resins
Cross linking:
It affects swelling & strength & solubility
Swelling:
When resin swells, polymer chain spreads apart
Polar solvents → swelling
Non-polar solvents → contraction
Swelling also affected electrolyte concentration.
Particle size and porosity
Increase in surface area & decrease in particle size will increase the rate of ion exchange.
Regeneration
Cation exchange resin are regenerated by treatment with acid, then washing with water.
Anion exchange resin are regenerated by treatment with NaOH, then washing with water until neutral.
EXPERIMENTAL SETUP OF ION EXCHANGE CHROMATOGRAPHY
Metrohm 850 Ion chromatography system
Instrumentation of ion exchange chromatography
PRACTICAL REQUIREMENTS
1.Column
» glass, stainless steel or polymers
2.Packing the column
» Wet packing method:
A slurry is prepared of the eluent with the stationary phase powder and then carefully poured into the column. Care must be taken to avoid air bubbles.
3.Application of the sample
After packing, sample is added to the top of the stationary phase, use syringe or pipette.
This layer is usually topped with a small layer of sand or with cotton or glass wool to protect the shape of the organic layer from the velocity of newly added eluent.
4.Mobile phase
Acids, alkalis, buffers…
6.Stationary phase
The ionic
The movement of molecules from one phase to another is called partitioning.
If two immiscible phases are placed adjacent to each other, the solute will distribute itself between two immiscible phases until equilibrium is attained; therefore no further transfer of solute occurs.
A presentation on column efficiency parameters in chromatography.. A part of gas chromatography in pharmacutical analysis..will be helpful for all mphrm students
Optical Rotation and Polarimeter by Dr. A. AmsavelDr. Amsavel A
Isomers and enantiomers
Specific Optical Rotation
Polarimeter
Instrumentation and Operation
Factors affect the Optical Rotation
Calibration
Application Specifically Pharmaceutical Industries
Quadrupole and Time of Flight Mass analysers.Gagangowda58
Description about important mass analysers Quadrupole and TOF: Principle, Construction and Working, Advantages and Disadvantages and their Applications.
Instrumentation of HPLC, principle by kk sahuKAUSHAL SAHU
INTRODUCTION
Instrumentation of HPLC
TYPES OF HPLC
PARAMETERS
APPLICATION
CONCLUSION
REFERENCE
High-performance liquid chromatography ( HPLC) is a specific form of column chromatography generally used in biochemistry and analysis to separate, identify, and quantify the active compounds.
HPLC mainly utilizes a column that holds packing material (stationary phase), a pump that moves the mobile phase(s) through the column, and a detector that shows the retention times of the molecules.
Notes* for the subject 'Advanced Pharmaceutical Analysis'Sanathoiba Singha
As per the syllabus prescribed by Rajiv Gandhi University of Health Sciences, Karnataka, for M. Pharm (Pharmaceutical Analysis) 1st semester.
*not all topics have been included in this collection of notes.
As per the syllabus prescribed by Rajiv Gandhi University of Health Sciences, Karnataka, for M. Pharm (Pharmaceutical Analysis), 1st semester.
*not all topics have been covered in this file.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
pKa and log p determination
1. ‘pKa and log P determination’
Presented by: Facilitated to:
Mr. L. Sanathoiba Singha
M. Pharm 1st Semester
Department of Pharmaceutical Analysis.
Dr. C. Sreedhar
Head of Department
Department of Pharmaceutical Analysis.
Karnataka College of Pharmacy
Bengaluru-64, Karnataka.
1
2. pKa (Logarithmic acid dissociation constant)
Introduction:
• Understanding the concept of ‘Ka’ before ‘pKa’
• Ka or acid dissociation constant is a quantitative measurement of the strength of an acid in solution.
• Let us consider the dissociation of the compound ‘HA’
HA ⇌ A- + H+
The Ka for this reaction will be given by:
Ka =
[A−][H+]
[HA]
• Expressing acidity in terms of Ka can be inconvenient for practical purposes, therefore, pKa is used.
• pKa can be defined as ‘the negative base-10 logarithm of acid dissociation constant (Ka) of a solution’.
pKa = -log10Ka
• Example:
The Ka constant for acetic acid is 0.0000158, but the pKa constant is 4.8, which is a simpler expression.
The smaller the pKa value, the stronger the acid.
The pKa value of lactic acid is about 3.8, so that means lactic acid is stronger than acetic acid. 2
3. 3
• A weak acid has a pKa value in the approximate range of -2 to 12 in water.
• Acids with a pKa value of less than about -2 are said to be strong acids.
Methods of pKa determination:
1. Potentiometric titration-
• In potentiometric titration, a sample is titrated with acid
or base using a pH electrode to monitor the course of
titration.
• The pKa value is calculated from the change in shape of
the titration curve compared with that of blank titration
without a sample present.
• Relationship between pH and pKa:
pH = pKa+log10
[A−]
[HA]
Fig.1. Titration curve of pH vs volume of titrant.
4. 4
2. Spectrophotometric methods-
• Main advantage is higher sensitivity.
• The compound must contain a UV-active chromophore close enough to the site of the acid–base function in the molecule.
• Spectral data are recorded continuously during the course of titration by a diode-array spectrometer.
• The absorption spectra of the sample changes during the course of the titration to reflect the concentration of neutral and
ionized species present.
• The largest change in absorbance occurs at the pH corresponding to a pKa value.
• The determination of pKa values by UV–VIS assumes that the solute of interest is pure or that its impurities do not absorb
in the UV–VIS range, since the spectra of impurities can overlap with those corresponding to the solutes of interest.
3. NMR titration-
• The protonation of a basic site leads to electronic deshielding effects on the adjacent NMR-active nuclei.
• The average chemical shifts of all the measurable NMR-active nuclei, as a function of pH, are expected to reflect the
fractional protonation of each basic group of a molecule.
• NMR titrations have not yet been applied to the pKa determination of APIs.
5. 5
3. Liquid chromatography (LC)-
• LC is used as a powerful technique for the determination of dissociation constants, as it requires only a small quantity of
compounds.
• Studied samples do not need to be pure and poor water solubility is not a serious drawback.
• This method does not include measuring solute or titrant concentrations, just retention times.
• Also, calculation is straightforward and independent of solute purity.
4. Computational methods-
• Theoretical pKa values can be calculated by computational methods (e.g., SPARC and and ACD/Lab).
• ARChem’s SPARC software is an on-line calculator that estimates the macroscopic and microscopic pKa of any organic
compound solely from its chemical structure.
• ACD/Lab pKa is a software program that calculates accurate acid-base ionization constants (pKa values) under 25°C and
zero ionic strength in aqueous solutions for almost any organic structure.
6. 6
Applications of pKa:
• The pKa values of proteins and amino acid side chains are of major importance for the activity of enzymes and the stability of
proteins.
• Buffer solutions are used extensively to provide solutions at or near the physiological pH for the study of biochemical
reactions; the design of these solutions depends on a knowledge of the pKa values of their components.
• In pharmacology, ionization of a compound alters its physical behaviour and macro properties. This is exploited in drug
development to increase the concentration of a compound in the blood by adjusting the pKa of an ionizable group.
• Knowledge of pKa values is important for the understanding of coordination complexes, which are formed by the interaction of a
metal ion with a ligand.
• In chemical oceanography in order to quantify the solubility of iron(III) in seawater at various salinities, the pKa values for the
formation of the iron(III) hydrolysis products Fe(OH)2+, Fe(OH)+
2 and Fe(OH)3 are determined.
7. 7
pKa determination for aspirin:
Requirements- Aspirin, ethanol, sodium hydroxide, pH meter.
Principle- Aspirin is a weak acid and partially ionizes in water.
HA + H2O ↔ H3O+ + A-
It’s acid dissociation constant, Ka is given by:
Ka =
[A−][H3O+]
[HA]
Aspirin and sodium hydroxide react in a 1:1 mole ratio:
CH3OCOC6H4COOH + NaOH → CH3OCOC6H4COONa + H2O
Method-
• A burette is filled with 0.1M sodium hydroxide solution.
• 0.36g of aspirin is weighed in 250ml beaker and 10ml of 95% ethanol is added and volume is made up with deionized water.
• 2ml portions of sodium hydroxide solution is added from burette to the beaker, stirring well between each additions and recording
the pH using a pH meter.
• The pH begins to rise rapidly near the end-point.
• After adding 18ml of sodium hydroxide solution, addition is continued in 0.5ml portions.
• After adding about 22ml, additions in 2ml portions is started again.
• The addition is continued until total of 36ml has been added.
8. 8
Processing data-
• A graph of pH against volume of 0.1M sodium
hydroxide is plotted.
• The end-point is calculated from the graph of titration.
• This is checked against the expected value by
calculating the number of moles of aspirin used
(relative molecular mass of aspirin = 180) and
therefore the volume of 0.1M sodium hydroxide
solution needed to react with it in a 1:1 mole ratio.
• From the graph, the pH is estimated at half-way point
of the titration. This gives a value for the pKa of aspirin.
Volume of 0.1M sodium hydroxide
Fig.2. Titration graph for aspirin against 0.1M sodium hydroxide solution.
9. 9
Log P (Logarithm of partition-coefficient)
Introduction:
• Partition coefficient, abbreviated as P, is defined as a particular ratio of the concentrations of a solute between two immiscible
solvents at equilibrium.
• The logarithm of this ratio is thus ‘log P’.
log Pow = log
[unionized solute]o
[unionized solute]w
• This ratio is therefore a measure of the difference in solubility of the compound in these two phases.
• The partition-coefficient generally refers to the concentration ratio of unionized species of the compound.
• When one of the solvents is water and the other is a non-polar solvent, then the log P value is a measure of lipophilicity or
hydrophobicity.
Choice of solvents:
• The choice of partition solvent has been subject to debate in recent years.
• The most commonly used solvent has been octan-1-ol or octanol.
• Octanol was chosen as a simple model of a phospholipid membrane.
10. 10
• Hydrophobic drugs with high octanol/water partition coefficients are mainly distributed to hydrophobic areas such as
lipid bilayers of cells.
• Hydrophilic drugs with low octanol/water partition coefficients are found primarily in aqueous regions such as blood
serum.
• If one of the solvents is a gas and the other a liquid, a gas/liquid partition coefficient can be determined e.g. the
blood/gas partition coefficient of a general anesthetic measures how easily the anesthetic passes from gas to blood.
Component log Pow(octanol/water) T (°C)
Acetamide -1.16 25
Methanol -0.81 19
Formic acid -0.41 25
Diethyl ether 0.83 20
p-Dichlorobenzene 3.37 25
Hexamethylbenzene 4.61 25
Table 2. Partition coefficient data of some compounds.
11. 11
Measurement of log P:
1. log P by Shake Flask-
• The shake flask method is the oldest and most tedious way of measuring log P values.
• Equimolar quantities of drug are added into equal volumes each of n-octanol and water.
• It is very important to pre-saturate the solvents in prolonged shake-flask experiments.
• The experiment must be performed over 3 days or more to ensure equilibrium is reached.
• The phases are separated and absorbance is measured and log P is calculated from formula for P.
2. log P by HPLC-
• Compounds with known Log P's are injected onto a C18 reverse phase HPLC column and their capacity factors used to
create a calibration curve.
• Unknown compounds are then injected and their capacity factors used to predict log P.
3. pH metric-
• This technique determine lipophilicity pH profiles directly from a single acid-base titration in a two phase water-organic
solvent system.
• Hence, a single experiment can be used to measure the log P.
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4. Prediction-
• QSAR (Quantitative Structure Activity Relationship) can be used to derive partition coefficients.
• Estimates of partition coefficients can be made using a variety of methods including fragment based, atom based
and knowledge based that rely soley on knowledge of the structure of the compound.
Optimum log P values for certain classes of drugs:
• Optimum CNS penetration - log P = 2±0.7
• Optimum oral absorption - log P = 1.8
• Optimum intestinal absorption - log P =1.35
• Optimum colonic absorption - log P = 1.32
• Optimum sub lingual absorption - log P = 5.5
• Optimum percutaneous absorption - log P = 2.6
For reasonable absorption log P should be below 5
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Applications of log P:
• In pharmacology, log P strongly affects how easily the drug can reach its intended target in the body, how strong an effect it
will have once it reaches its target and how long it will remain in the body in an active form. Hence, It is an essential criteria in
pre-clinical drug discovery for assessment of new drug candidates.
• In pharmacokinetics, log P has a strong influence on ADME properties of a drug.
• In environmental science partition coefficient can be used to predict the mobility of radioactive compounds in groundwater
and hence study water pollution and its toxicity to animals and aquatic life.
• In metallurgy, partition coefficient is an important factor in determining how different impurities are distributed between
molten and solidified metal.
• In FMCG, partition coefficient is taken into account e.g.in the formulation of topical ointments, dyes, hair colors, etc.
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Log P determination of Levofloxacin:
Determined by shake flask method in n-octanol:water system
10mg of drug is added into 50ml each of n-octanol and water
The mixture is shaken for 24 hours until equilibrium is reached
Phases are separated using a separating funnel, filtered and suitably diluted
Absorbance is measured at 258nm using UV spectrophotometer
Partition coefficient (P) is calculated using:
P =
Co
Cw
and hence log P can be calculated.
NOTE:
Using similar techniques for log P determination of levofloxacin, log P can be found out for salicylic acid, various steroids, antibiotics,
etc.
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Log P determination of Permethrin:
Method- Reverse phase HPLC
Preparation of diluent- Methanol and water is taken in the ratio 95:10 v/v.
Preparation of reference standard solution- Equimolar solutions of thiourea, triphenylamine, phenanthrene, naphthalene, phenol and
methyl benzoate are prepared into different 10ml volumetric flasks, using the above diluent solution.
Preparation of permethrin sample solution- The solution is made using 2.95mg of permethrin in 10ml volumetric flask, using the
diluent solution.
Determination of log P- The capacity factor, k´ for each reference standard and test item can be calculated for the HPLC system from
their respective retention times.
k´ =
(𝑡𝑅−t0)
t0
Where, k´= capacity factor
𝑡 𝑅 = retention time (min)
t0 = dead time (min)
• A correlation graph is generated of ‘log k´’ vs ‘log Pow’ for the reference standards.
• The log Pow for permethrin is the interpolated from the correlation graph.
NOTE:
• Capacity factor, k´ - It is an indication of how long
a compound can be retained by the stationary
phase.
• Retention time, 𝑡 𝑅 - It is the measure of time taken
for a solute to pass through a chromatography
column.
• Dead time, t0 - It is the elution time of an
unretained component
17. 17
REFERENCES:
Svehla G. Vogel’s Textbook of Macro and Semimicro Qualitative Inorganic Analysis. Longman Group Limited, London. 1975 (5).
28-31:130-131.
Babić S, Horvat A. J. M, Pavlović D. M and Kaštelan-Macan M. Determination of pKa Values of Active Pharmaceutical
Ingredients. Trends in Analytical Chemistry, 2007, 26 (11). 1043-1060.
Wikipedia contributors. (2018, August 31). Acid dissociation constant. In Wikipedia, The Free Encyclopedia. Retrieved 13:24,
September 1, 2018, from https://en.wikipedia.org/w/index.php?title=Acid_dissociation_constant&oldid=857405027 .
Wikipedia contributors. (2018, June 14). Partition coefficient. In Wikipedia, The Free Encyclopedia. Retrieved 19:51, September 1,
2018, from https://en.wikipedia.org/w/index.php?title=Partition_coefficient&oldid=845795904.
Mark E. A Guide to log P and pKa Measurements and Their Use. Mark’s Analytical Chemistry, 2006.
Shahwal V. K, Dubey B. K and Bhoumick M. Preformulation Study of Levofloxacin. International Journal of Advances in
Pharmaceutics, 2012, 1(1). 1-8.
Rao T. N, Srinivasarao T and Botsa P. A Simple Reverse Phase HPLC Method for Determination of Partition Coefficient of
Permethrin Pesticide. Chromatography, 2016, 1 (1). 1-5.
Jeffery G. H, Bassett J, Mendham J and Denny R. C. Vogel’s Textbook of Quantitative Chemical Analysis. Longman Scientific &
Technical, England. 1989 (5). 31-33:162-163.