This document discusses pH, buffers, and isotonic solutions. It provides information on pH scales, how pH is determined through electrometric and colorimetric methods, and applications of buffers. Buffer solutions are defined as those that resist changes in pH when small amounts of acid or base are added. The mechanisms and properties of buffer action are explained. The Henderson-Hasselbalch equation relating the pH of a buffer solution to the ratio of concentrations of its weak acid and salt is derived. Factors affecting buffer capacity are also outlined.
Benzene and its derivatives- According to PCI Syllabus Ganesh Mote
Benzene history, nomenclature, orbital structure, resonance structure, kekule structure,synthetic evidences, structural and analytical evidences, Directive effect of benzene, structure and uses of DDT, BHC, saccharine
Benzene and its derivatives- According to PCI Syllabus Ganesh Mote
Benzene history, nomenclature, orbital structure, resonance structure, kekule structure,synthetic evidences, structural and analytical evidences, Directive effect of benzene, structure and uses of DDT, BHC, saccharine
Complexation and Protein Binding [Part-2](Method of analysis, Complexation a...Ms. Pooja Bhandare
Method of Analysis: Methods of continuous variation / JOB’S method of continuous variation.
pH titration method.
Distribution method.
Solubility method.
Spectroscopy and charge transfer complexation.
Miscellaneous method
State of matter and properties of matter (Part-6)(Relative humidity, Liquid ...Ms. Pooja Bhandare
RELATIVE HUMIDITY, Humidity, Wet and Dry Hygrometer, LIQUID COMPLEX, LIQUID CRYSTALS, Types of liquid crystals, GLASSY STATES, Characteristics glassy state, Types of glassy state, What is the Glass Transition Temperature?
State of matter and properties of matter (Part-2) (Latent Heat, Vapour pressu...Ms. Pooja Bhandare
Latent Heat, Vapour pressure, Factor affecting vapour pressure, Surface area, Types of molecule, Temperature and Intermolecular forces, Sublimation Critical point
Solubility of drugs: Solubility expressions, mechanisms of solute solvent interactions, ideal solubility parameters, solvation & association, quantitative approach to the factors
influencing solubility of drugs, diffusion principles in biological systems. Solubility
of gas in liquids, solubility of liquids in liquids, (Binary solutions, ideal solutions)
Raoult’s law, real solutions. Partially miscible liquids, Critical solution temperature . Distribution law, its limitations and applications
Surface and Interfacial tension [Part-3(a)](Measurement of Surface and Inter...Ms. Pooja Bhandare
MEASUREMENT OF SURFACE AND INTERFACIAL TENSION
Capillary Rise Method, Drop Count and Weight Method.
Wilhelmy Plate Methods ,The DuNouy Ring Method.
Capillary Rise Method: Upward force due to surface tension: Drop count and Weight method Downward Force: Drop weight method: Drop count method
Quantitative approach to the to the factor influcing solubility of drug; (Sol...Ms. Pooja Bhandare
Quantitative approach to the to the factor influcing solubility of drugs, Temperature,Nature of solvent, The boiling point of the liquids and the melting point of solids,Crystal properties:
Particle size (surface area ) of drug particles: The influence of substituent’s in molecular structures, Molecular size:
. pH :
Solubility of liquids in liquids, The term miscibility refers to the mutual solubility of the component of liquid - liquid system, Raoult’s Law, Raoult’s law may be mathematically expressed as: Ideal solution, Real solution
4th (30.10.2014) on eutectic mixture by Diptarco SinghaDiptarco Singha
this ppt is very simple and has immence importance in physical pharmacy. it has been prepared based on the syllabus of WBUT & consists of informations of elimentary label...
Complexation and Protein Binding [Part-2](Method of analysis, Complexation a...Ms. Pooja Bhandare
Method of Analysis: Methods of continuous variation / JOB’S method of continuous variation.
pH titration method.
Distribution method.
Solubility method.
Spectroscopy and charge transfer complexation.
Miscellaneous method
State of matter and properties of matter (Part-6)(Relative humidity, Liquid ...Ms. Pooja Bhandare
RELATIVE HUMIDITY, Humidity, Wet and Dry Hygrometer, LIQUID COMPLEX, LIQUID CRYSTALS, Types of liquid crystals, GLASSY STATES, Characteristics glassy state, Types of glassy state, What is the Glass Transition Temperature?
State of matter and properties of matter (Part-2) (Latent Heat, Vapour pressu...Ms. Pooja Bhandare
Latent Heat, Vapour pressure, Factor affecting vapour pressure, Surface area, Types of molecule, Temperature and Intermolecular forces, Sublimation Critical point
Solubility of drugs: Solubility expressions, mechanisms of solute solvent interactions, ideal solubility parameters, solvation & association, quantitative approach to the factors
influencing solubility of drugs, diffusion principles in biological systems. Solubility
of gas in liquids, solubility of liquids in liquids, (Binary solutions, ideal solutions)
Raoult’s law, real solutions. Partially miscible liquids, Critical solution temperature . Distribution law, its limitations and applications
Surface and Interfacial tension [Part-3(a)](Measurement of Surface and Inter...Ms. Pooja Bhandare
MEASUREMENT OF SURFACE AND INTERFACIAL TENSION
Capillary Rise Method, Drop Count and Weight Method.
Wilhelmy Plate Methods ,The DuNouy Ring Method.
Capillary Rise Method: Upward force due to surface tension: Drop count and Weight method Downward Force: Drop weight method: Drop count method
Quantitative approach to the to the factor influcing solubility of drug; (Sol...Ms. Pooja Bhandare
Quantitative approach to the to the factor influcing solubility of drugs, Temperature,Nature of solvent, The boiling point of the liquids and the melting point of solids,Crystal properties:
Particle size (surface area ) of drug particles: The influence of substituent’s in molecular structures, Molecular size:
. pH :
Solubility of liquids in liquids, The term miscibility refers to the mutual solubility of the component of liquid - liquid system, Raoult’s Law, Raoult’s law may be mathematically expressed as: Ideal solution, Real solution
4th (30.10.2014) on eutectic mixture by Diptarco SinghaDiptarco Singha
this ppt is very simple and has immence importance in physical pharmacy. it has been prepared based on the syllabus of WBUT & consists of informations of elimentary label...
The objective is to understand the buffer equation, factors influencing the pH of buffer solutions, Buffer capacity, Buffer in pharmaceutical systems and biologic system, Influence of buffer capacity and pH on tissue, pH and solubility
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pH is a measure of how acidic or alkaline a solution is. In pure water at room temperature, a small fraction (about two out of every billion) of the water molecules (H 2 O, or really, H-O-H) splits, or dissociates , spontaneously, into one positively charged hydrogen ion (H + ) and one negatively charged hydroxide ion (OH - ) each.For more information please log on http://cutt.us/4ObJ
Chem 132 principles of chemistry lab ii montgomeryAtherstonez
FOR MORE CLASSES VISIT
tutorialoutletdotcom
Principles of Chemistry Lab II Montgomery College, Rockville
Acids and Bases, pH, Buffers and Hydrolysis Introduction
Acids and Bases
Aqueous solutions of acids and bases are recognized as “acidic” or “basic” because they contain
appreciable concentrations of either hydronium (H3O+) or hydroxide (OH–) ions. Hydronium ions are
produced from the reaction of covalent molecules like HCl with water.
This PDF file content is about States of matter and its Properties as per the PCI syllabus for B.Pharm Second year for the subject Physical Pharmaceutics
This PDF file content is about complexation and Protein bindings as per the PCI syllabus for B.Pharm Second year for the subject Physical Pharmaceutics
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
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.
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.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...
Ph, buffers & isotonic solution
1. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
UNIT-V
pH, buffers
&
Isotonic solutions
2. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
pH, buffers and Isotonic solutions:
Sorensen’s pH scale, pH determination (electrometric and calorimetric),
applications of buffers, buffer equation, buffer capacity, buffers in
pharmaceutical and biological systems, buffered isotonic solutions.
3. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
For water molecules undergoing ionisation we can write;
According to law of mass action;
But, Only one out of 550 water molecules is undergoing ionisation. It
means that [H20] is constant.
Where Kw is called ionic product of water and its value is 1 × 10-14 at
25 °C, I.e.,
𝑯 𝟐 𝑶 ⇋ 𝑯+ + 𝑶𝑯−
𝑲 =
𝑯+
𝑶𝑯−
𝑯 𝟐 𝑶
𝑲 𝑯 𝟐 𝑶 = 𝑯+
𝑶𝑯−
𝑲𝒘 = 𝑯+ 𝑶𝑯−
𝟏 × 𝟏𝟎−𝟏𝟒 = 𝑯+ 𝑶𝑯−
4. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Pure water has equal concentration of [H+] and [OH-] ions. Thus,
or
Thus, for neutral water, [H+] ion concentration is 10-7 g ion/litre
The solution becomes acidic if [H+] > l × 10-7 g ion/litre and
alkaline if [H+] < l × 10-7 g ion/litre
Reverse is true when solutions [OH-] > l × 10-7 g ion/litre. for
alkaline solutions.
𝟏𝟎−𝟏𝟒
= 𝑯+
𝑯+
𝑯+
= 𝟏𝟎−𝟕
5. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Hydrogen ion concentration values are complex figures to write and
use in calculations since they contain negative powers of 10.
In 1909, Sorensen introduced the term pH.
The pH expresses [H+] of an aqueous solution as a logarithmic
function.
The pH of a solution equals the negative of the logarithm to the
base10 of its hydrogen ion concentration, I.e., pH = -log10 [H+]
pH offers a convenient mechanism of expressing a wide range of [H+]
in small positive numbers.
The letter, p in term ‘pH’ stands for German word “ potenz ” (power),
so pH is abbreviation for “power of hydrogen”.
6. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Relation between pH, [H+] and [OH-] concentration in Moles/L at 25 °C Temperature
7. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The PH scale from 0 to 14 covers all the hydrogen ion concentrations.
8. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The Electrometric Method is the most accurate of the
methods employed for the determination of Hydrogen Ion
Concentration.
It is the accepted method for research and laboratory work
requiring pH measurements accurate to 0.1 to 0.001 pH.
1. Electrometric Method
pH determination
Generally pH is determined by following methods;
1. Electrometric Method
2. Colorimetric
9. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Principle
The basic principle of the electrometric pH measurement is
determination of the activity of the hydrogen ion by potentiometric
measurement using a standard hydrogen electrode and a reference
electrode.
pH meter detects the change in potential and determine the hydrogen
ion by equation;
𝑬 = 𝑬 𝟎 +
𝟐. 𝟑𝟎𝟑 𝑹𝑻
𝒏
× 𝑭 × log
𝒖𝒏𝒌𝒏𝒐𝒘𝒏 𝑯+
𝒊𝒏𝒕𝒆𝒓𝒏𝒂𝒍 𝑯+
Where,
E = Total potential difference
E0 = Reference potential
R = Gas constant
n = no. of electrons
F = Faraday’s constant
10. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Apparatus:
pH meter consisting of
potentiometer, a glass electrode,
a reference electrode and a
temperature compensating
device.
Glass electrode: The sensor
electrode is bulb of special glass
containing a fixed concentration
of HCl and a buffered chloride
solution in contact with an
internal reference electrode.
11. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
12. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The electrodes commonly used are the Hydrogen Electrode, the
Quinhydrone Electrode and the Calomel Electrode.
The usual combinations are the Hydrogen-Calomel Electrode and
the Quinhydrone-Calomel Electrode Assemblies.
13. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
14. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Procedure
Before use, remove electrode from storage solution, rinse, and
blot, dry with a soft tissue paper.
Calibrate the instrument with standard buffer solution. (Ex:
KCl solution of pH 7.0)
Once the instrument is calibrated remove the electrode from
standard solution; rinse, blot and dry.
Dip the electrode in the sample whose pH has to be measured.
Stir the sample to ensure homogeneity and to minimize CO2
entrainment.
Note down the reading (pH) from the pH meter.
15. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Colorimetric Determination of the pH
16. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The basis of colorimetric analysis is the variation in the intensity
of the colour of a solution with changes in concentration (or pH).
The colour may be due to an inherent property of the constituent
itself (e.g. MnO4− is purple) or it may be due to the formation of
a Coloured compound as the result of the addition of a suitable
reagent (e.g. indicator).
By comparing the intensity of the colour of a solution of
unknown concentration (or pH) with the intensities of solutions
of known concentrations (or pH), the concentration of an
unknown solution may be determined.
Colorimetric Determination of the pH
17. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
A buffer solution is one which resist a change of pH on
addition of an acid or alkali or, on dilution with a solvent.
The pH of pure water is 7 and the water has no buffer action.
A buffer solution consists of a mixture of weak acid and its salt or
of a weak base and its salt. To such solution when small amount of
acid or alkali is added no significant change in the pH takes place.
Buffer solutions can be prepared either by mixing a weak acid
with its salt or a weak base with its salt.
Buffer solution
18. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Types of Buffer Solutions
These are mainly of following two types:
1. Acidic Buffer Solution: The solution having a mixture of weak
acid (e.g., acetic acid) and its salt (e.g., sodium acetate) is known
as acidic buffer.
2. Basic Buffer Solution: The solution having a mixture of weak
base (e, g., ammonium hydroxide) and its salt (e, g. Ammonium
chloride) is a basic buffer.
19. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Properties of buffer solutions
1. The pH of buffer solution remains constant.
The pH of solution does not change on dilution.
The pH does not change even after addition of small
quantities of acids or bases.
The pH of buffer solution does not change on keeping for
long time.
2. The pH of solution remaining constant is useful in number of
chemical reactions.
20. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Buffer action
Buffer solutions undergo only small changes of pH on the addition
of small amounts of acid or base.
For example,
If 1 ml of 0.01 M hydrochloric acid is added to 1 litre of pure
water, the pH is reduced to 5.0 from 7.0
On the other hand, if the acid is added to 0.001 M buffer
solution containing equal quantities of acetic acid and sodium
acetate in water the pH change is only by 0.09 units.
From this, it is clear that a buffer solution resists change of pH
upon the addition of small quantities of acid or alkali.
21. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Mechanism of buffer action
If a small quantity of 0.1N HCI is added to the buffer solution, the
base ties up the hydrogen ions released by HCl.
If an alkali (NaOH) is added to the buffer solution, the free acid of
the buffer solution neutralises the base added
Thus, the change in PH is resisted by the addition of small
quantities of strong acid.
(𝑯𝑪𝒍 + 𝑯 𝟐 𝑶 ⇋ 𝑯 𝟑 𝑶+ + 𝑪𝒍−)
𝑪𝑯 𝟑 𝑪𝑶𝑶
−
+ 𝑯 𝟑 𝑶+
⇋ 𝑪𝑯 𝟑 𝑪𝑶𝑶𝑯 + 𝑯 𝟐 𝑶
𝑪𝑯 𝟑 𝑪𝑶𝑶𝑯 + 𝑵𝒂𝑶𝑯 ⇋ 𝑪𝑯 𝟑 𝑪𝑶𝑶𝑵𝒂 + 𝑯 𝟐 𝑶
22. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Buffer equation
Buffer equation may be obtained by considering the effect of
sodium acetate on the ionisation of acetic acid (the salt and the
acid have an ion common with them i.e. Acetate ion, CH3COO-)
The dissociation constant for the acid is given as
𝑪𝑯 𝟑 𝑪𝑶𝑶𝑯 ⇋ 𝑪𝑯 𝟑 𝑪𝑶𝑶
−
+ 𝑯 𝟑 𝑶+
𝑲 𝒂 =
𝑪𝑯 𝟑 𝑪𝑶𝑶
−
𝑯 𝟑 𝑶+
𝑪𝑯 𝟑 𝑪𝑶𝑶𝑯
= 𝟏. 𝟕𝟓 × 𝟏𝟎
− 𝟓
23. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
If sodium acetate is added to the acetic acid solution, it ionises to
produce acetate ions as;
and it results in the increase in the concentration of CH3COO-
momentarily.
To re-establish the constant Ka = 1.75 × 10-5, the hydrogen ion
term in the numerator is instantaneously decreased.
This results in the increase of concentration of CH3COOH in the
denominator i.e. The reaction
is favored. Thus the constant Ka remains unaltered.
𝐂𝐇 𝟑 𝐂𝐎𝐎𝐍𝐚 ⇋ 𝐂𝐇 𝟑 𝐂𝐎𝐎
−
+ 𝐍𝐚
+
𝑪𝑯 𝟑 𝑪𝑶𝑶
−
+ 𝑯 𝟑 𝑶+
⇋ 𝑪𝑯 𝟑 𝑪𝑶𝑶𝑯 + 𝑯 𝟐 𝑶
24. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The pH of the final solution (i.e. the buffer solution) is obtained from
the above equation.
By rearrangement
Since CH3COOH ionises only slightly (i.e. to an extent of 0.0000175
mole/liter), the concentration of CH3COOH may be considered to
represent the total concentration of acid in the solution and can be
replaced by [Acid].
The acetate ion (CH3COO-) is contributed entirely by sodium acetate
as the contribution by the acid is negligible, Therefore [CH3COO-]
may replaced by [salt]. Therefore;
𝑯 𝟑 𝑶+
= 𝑲 𝒂
𝑪𝑯 𝟑 𝑪𝑶𝑶𝑯
𝑪𝑯 𝟑 𝑪𝑶𝑶
−
𝑯 𝟑 𝑶+
= 𝑲 𝒂
𝒂𝒄𝒊𝒅
𝒔𝒂𝒍𝒕
25. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Expressing in logarithmic form,
log [H3O+] = log Ka + log [acid] - log [salt]
Reversing the sign
- log [H3O+] = - log Ka - log [acid] + log [Salt]
or
This is known as Henderson Hasselbalch equation for a weak acid and
its salt.
pH = pKa+ log
salt
acid
26. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
To know the effectiveness of a buffer on a quantitative basis, the term
buffer capacity (ß) is used. First introduced by van Slyke in 1922.
Buffer capacity is defined as the amount of acid or base that
must be added to the 1 liter buffer to produce a 1 unit change of pH.
Hence,
Where the d[B] is gram equivalent of strong acid or base added and
d[H] is pH change due to addition of acid or base.
The larger the buffer capacity, the more resistant the buffer is to
changes in pH.
The capacity of a given buffer is determined by the concentrations of
acid and salt and also by the ratio of acid/salt or base/salt.
β =
d B
d pH
Buffer capacity
27. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
1. Ratio of Salt/Acid or Base
2. Total buffer concentration
3. Temperature
4. Ionic strength
Factors affecting Buffer capacity
28. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Role of buffers in pharmacy
The buffers play an important role in pharmaceutical preparations to
ensure stable pH conditions for the medicinally active compound.
1. Solubility: Solubility of compounds can be frequently controlled by
providing a medium of suitable pH. The required pH is adjusted by
buffers.
E.g. Many inorganic salts such as salts of Fe+3, phosphates,
borates become soluble in acid media; but precipitate in alkaline
media.
2. Colour: Colour of many natural dyes, present in fluid extract or of
certain synthetic drugs has been found to be pH dependent. e.g., red
colour of cherry and raspberry syrups has been maintained at acidic
pH which becomes pale yellow to nearly colorless at alkaline pH.
29. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
3. Stability of certain compounds :
e.g.
i. Adrenaline with dissolved oxygen in presence may undergo
reductions with alkaline medium. So its solution for
injection is to be buffered to most stable pH range 2.5 - 5.
i. Ascorbic acid and penicillin are unstable in an alkaline pH.
Some compounds have been found to be structurally unstable within
certain PH ranges usually autoxidation, giving rise to insoluble solids
or gases,
e.g.,
i. Sodium thiosulphate and sodium polysulphide preparations
have to be stored at alkaline conditions to prevent
separation of sulphur.
ii. Nitrites become brown in acid media because of formation
of Coloured nitrogen oxides.
30. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
4. Patient comfort: Injectable and preparations for internal or external
use become irritating if their pH is different greatly from that normal
for the particular tissues involved. An extremely acid or alkaline pH
must be avoided because of tissue damage.
5. Activity of medicinal compounds: Optimum pH conditions for
activity of medicinal compounds have to be maintained.
e.g.
i. Buffering methylamine with sodium dihydrogen phosphate.
ii. Adjustment of the pH of sodium hypochlorite to lower
values tends to increase the germicidal effectiveness of the
preparation.
31. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Usually for the preparation of buffer solutions, weak bases and their
salts are not used since many bases are volatile and their solutions
have high temperature coefficients.
KCI is a neutral salt and is added to adjust the ionic strength of the
buffer system. Some pharmaceutical buffers are;
Pharmaceutical buffers
Buffers pH
HCI and KCl 1.2 to 2.2
HCI and potassium hydrogen phthalate 2.2 to 5.0
NaOH and potassium hydrogen phthalate 4.2 to 5.8
NaOH and potassium dihydrogen phosphate 5.8 to 8.0
Boric acid, NaOH and KCl 8.0 to 10.0
32. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Various buffer solutions used in the pharmaceutical formulations are
as follows;
Buffers pH
Acetic acid / sodium acetate 3.8 to 5.6
Phosphate acid/ sodium phosphate 5.0 to 8.0
Citric acid/ sodium citrate 1.2 to 6.6
Boric acid/ sodium borate 7.8 to 10.6
33. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Biologic Buffers
Blood pH is maintained at about 7.4 by the buffers present in plasma
as well as by the buffers in the erythrocytes.
The plasma contain carbonic acid/bicarbonate and acid/alkali sodium
salts of phosphoric acid as buffers.
In the erythrocytes, the buffers are haemoglobin/oxyhaemoglobin and
acid/alkali potassium salts of phosphoric acid.
Biological fluids pH
Blood 7.4 – 7.5
Tear 7.0 – 8.0
Urine 4.5 – 8.0
Gastric juice 1.5 – 3.5
Bile 6.0 – 8.5
Saliva 5.4 – 7.5
pH of some physiological
fluids are given in table;
34. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
The important biological buffer systems are the dihydrogen phosphate system and
the carbonic acid system.
1. The Phosphate Buffer System:
The phosphate buffer system operates in the internal fluid of all cells.
This buffer system consists of dihydrogen phosphate ions (H2PO4
-) as
hydrogen ion donor (acid) and hydrogen phosphate ions (HPO4
-2) as
hydrogen-ion acceptor (base).
These two ions are in equilibrium with each other as indicated by the
chemical equation given below.
If additional hydrogen ions enter the cellular fluid, they are consumed in
the reaction with HPO4
-2, and the equilibrium shifts to the left. If additional
hydroxide ions enter the cellular fluid, they react with H2PO4
-, producing
HPO4
-2 , and shifting the equilibrium to the right.
𝑯 𝟐 𝑷𝑶 𝟒(𝒂𝒒)
−
⇋ 𝑯(𝒂𝒒)
+
+ 𝑯𝑷𝑶 𝟒(𝒂𝒒)
−
35. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
2. The Carbonic Acid System:
Another biological fluid in which a buffer plays an important role in
maintaining PH is blood plasma.
In blood plasma, the carbonic acid and hydrogen carbonate ion equilibrium
buffers the PH.
In this buffer, carbonic acid (H2CO3) is the hydrogen ion donor (acid) and
hydrogen carbonate ion (HCO3
-) is hydrogen-ion acceptor (base). The
simultaneous equilibrium reaction is shown below.
This buffer functions in the same way as the phosphate buffer.
Additional H+ is consumed by HCO3
- and additional OH- is consumed by
H2CO3.
𝑯 𝟐 𝑪𝑶 𝟑(𝒂𝒒) ⇋ 𝑯(𝒂𝒒)
+
+ 𝑯𝑪𝑶 𝟑(𝒂𝒒)
−
36. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Buffered isotonic solution
Tonicity is a property of a solution about a membrane, and is equal to
the sum of the concentrations of the solutes which have the capacity
to exert an osmotic force across that membrane.
Tonicity depends on solute permeability.
If a semi-permeable membrane is used to separate solutions of
different solute concentrations, a phenomenon known as osmosis
occurs to establish concentration equilibrium.
The pressure driving this movement is called osmotic pressure and is
governed by the number of particles of solute in solution.
Tonicity is generally classified in three types;
1. Hypertonicity
2. Hypotonicity
3. Isotonicity
37. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Hypertonicity:
A solution having higher osmotic pressure than the body
fluids (or 0.9% NaCl solution) is known as hypertonic solution.
These solutions draw water from the body tissues to dilute and
establish equilibrium.
An animal cell in a hypertonic environment is surrounded by a
higher concentration of impermeable solute than exists in the
inside of the cell causing it to shrink.
38. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
For example,
If 2.0% NaCl solution is added to blood, osmotic pressure directs a net
movement of water out of the cell causing it to shrink (the shape of the cell
becomes distorted) and wrinkled, as water leaves the cell. This movement is
continued until the concentrations of salt on both sides of the membrane are
identical.
Hence, 2.0% NaCl solution is hypertonic with the blood,
39. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Hypotonicity:
A solution with low osmotic pressure than body fluids is
known as hypotonic solution.
Administration of a hypotonic solution produces swelling of tissues
as water is pulled to the biological cells (tissues or blood cells) from
dilute the hypertonic solution.
The effects of administering a hypotonic solution are generally
more severe than with hypertonic solutions, since ruptured cells can
never be repaired.
Hypotonic solutions show opposite effect compare to hypertonic
solutions that the net movement of water is into the cell causing
them to swell.
40. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
For example,
If 0.2% NaCl solution is added to blood, the cells get swelled and
burst.
Therefore, O. 2% NaCl solution is hypotonic with respect to the
blood.
41. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Isotonicity:
The solution that have the same osmotic pressure as that of
body fluids are said to be isotonic with the body fluid.
Body fluids such as blood and tears have osmotic pressure
corresponding to that of 0.9. % NaCl or 5% dextrose aqueous
solution thus, a 0.9% NaCl or 5% dextrose solution is called as
isosmotic or isotonic.
The term isotonic means equal tone, and is used interchangeably
with isosmotic regarding specific body fluids.
A cell in an isotonic environment is in a state of equilibrium with its
surroundings with respect to osmotic pressure. When the amount of
impermeable solute is same on the inside and outside of the cell,
osmotic pressure becomes equal.
42. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
For example,
On addition of 0.9 g NaCl/100 mL (0.9%) into blood, the cells
retain their normal size.
43. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
Methods Used to Determine Tonicity Value:
Many chemicals and drugs are used in the pharmaceutical
formulations. These substances contribute to the tonicity of the
solution. Hence methods are needed to verify the tonicity and adjust
isotonicity.
Two of the methods used to determine tonicity value are as follows.
1. Hemolytic method
2. Cryoscopic method
44. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
1) Hemolytic method:
Isotonicity value is calculated by using hemolytic method in
which the effect of various solutions of drug is observed on the
appearance of red blood cells suspended in solutions.
In this method, RBC's are suspended in various solutions and
the appearance of RBC's is observed for swelling, bursting,
shrinking and wrinkling of the blood cells.
In hypotonic solutions, oxyhaemoglobin released is
proportional to number of cells hemolyzed; in case of
hypertonic solutions, the cells shrink and become wrinkled
where as in case of isotonic solutions the cells do not change
their morphology.
45. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
2) Cryoscopic method:
Isotonicity values can be determined from the colligative
properties of the solutions.
For this purpose, freezing point depression property is most
extensively used.
The freezing point of water is 0º C, and when any substance
such as NaCl is added to it the freezing point of water decreases.
The freezing point depression ∆Tf of blood is -0.52º C.
Hence the ∆Tf value of the drug solution must be - 0.52º C. This
solution shows osmotic pressure equal to the blood and hence
RBC’s morphology found to be unchanged.