TEETHANKER MAHAVEER COLLEGE OF PHARMACY

TEERTHANKER MAHAVEER UNIVERSITY

PHYSICAL PHARMACEUTICS I (BPHT302) CT II

Model answers of CT II questions

Normality-

As per the standard definition, normality is described as the number of gram or mole equivalents of
solute present in one litre of a solution.

Mole fraction-

the mole fraction or molar fraction (xi or χi) is defined as unit of the amount of a constituent

(expressed in moles), ni, divided by the total amount of all constituents in a mixture (also
expressed in moles), ntot.[1] This expression is given below:
xi = ni/ntot

Molarity-

Molar concentration (also called molarity, amount concentration or substance

concentration) is a measure of the concentration of a chemical species, in particular of
a solute in a solution, in terms of amount of substance per unit volume of solution. In chemistry,
the most commonly used unit for molarity is the number of moles per liter, having the unit
symbol mol/L or mol⋅dm−3 in SI unit. A solution with a concentration of 1 mol/L is said to be
1 molar, commonly designated as 1 M.

Buffer equation

Buffers have properties that the pH of buffer solution remains constant, does not change with the
dilution, and on the addition of small quantities of acids or bases as well as on storage for long
period.

In the case of moderate pH solutions addition of small amounts of acids or bases leads to
absorption by buffer with only a slight pH change. For solutions having extreme pH values,
small amounts of solutions of strong acids or bases for example, in the case of pH 1, acid
concentration is relatively high (0.1 M) and a small addition of acid or base doesn’t change the
pH of such solution significantly. In most cases, we need to know the pKa of the weak acid to do
these calculations. The pH of the buffer solution can be obtained by rearranging the equation (1)
for dissociation constant:

equation (1)
Since acetic acid ionizes very slightly, the concentration of acetic acid can be considered as the
total concentration of acid in the solution. The term [CH3COOH] can be replaced by the term
[Acid] and the term [CH3COO– ] can also be replaced by [Salt]. Thus,

equation (2)
To calculate the pH of buffer solution containing both acid and its conjugate base the
dissociation constant equation can be rearranged and rewritten as follows:

equation (3)
where [HA] is the concentration of acid and [A–] is the concentration of its conjugate base.
Expressing equation (3) in the logarithmic form it becomes,

equation (4)
i.e.

PH-

What Is pH?
Before we talk about how pH is measured, let's briefly discuss what pH values mean. pH is
actually an abbreviation for 'potential of hydrogen.' It is a numerical value assigned to a solution
that tells us how acidic or basic that solution is. The pH scale ranges from 0 to 14; pH values that
are less than 7 are defined as being acidic, while pH values greater than 7 are defined as basic. A
pH that is a perfect 7 is said to be neutral and is neither acidic or basic.
Methods of pH Determination
Now that we know what pH is and have some insight into its numerical values, let's discuss the
various methods and instrumentation available for measuring the pH of a solution.
1. Conductivity Meters
A conductivity meter is an instrument that detects the presence of electrical current within a
solution. By definition, acids release hydrogen ions in solution, and bases release hydroxide (-
OH) ions. Both of these species possess an electrical charge, and it's the job of the conductivity
meter to not only detect the charge but also calculate the relative concentration of the ions. By
knowing the concentration, the instrument is able to calculate the pH of the solution.
2. pH Meter
Another way chemists determine the pH of a solution is by using a pH meter. A pH meter is
very similar to a conductivity meter. However, the pH meter specifically looks for and detects
the hydrogen ion concentration within a solution. Usually a pH meter must be calibrated to
ensure its accuracy, and this is typically done by using a standard solution whose exact pH is
known. The meter is set to that specific value and then unknown pH values are determined in
reference to the standard.
3. pH Indicators
What if we didn't necessarily need to know the exact numerical value of the pH of a solution, but
just if it were acidic or basic? A pH indicator is a compound that, depending on the nature of the
solution environment it's in, causes the solution to be different colors. For example, methyl
orange is an organic compound that turns the solution different colors based on the pH.

Clathrates-

A clathrate is a chemical substance consisting of a lattice that traps or contains molecules. The

word clathrate is derived from the Latin clathratus (clatratus), meaning ‘with bars, latticed’.
[1]
 Most clathrate compounds are polymeric and completely envelop the guest molecule, but in
modern usage clathrates also include host–guest complexes and inclusion compounds.
[2]
 According to IUPAC, clathrates are inclusion compounds "in which the guest molecule is in a
cage formed by the host molecule or by a lattice of host molecules."[3] The term refers to many
molecular hosts, including calixarenes and cyclodextrins and even some inorganic polymers such
as zeolites.
Many clathrates are derived from organic hydrogen-bonded frameworks. These frameworks are
prepared from molecules that "self-associate" by multiple hydrogen-bonding interactions.
 TEETHANKER MAHAVEER COLLEGE OF PHARMACY

TEERTHANKER MAHAVEER UNIVERSITY

PHYSICAL PHARMACEUTICS I (BPHT302) CT I

Model answers of CT I questions

CHELATES

A chelate is an organic compound formed when a polydentate ligand bonds to a

central metal atom. Chelation, according to the IUPAC, involves the formation of two or more
separate coordinate bonds between the ligand and central atom. The ligands are terms of
chelating agents, chelants, chelators, or sequestering agents.

Uses of Chelates

Chelation therapy is used to remove toxic metals, as in heavy metal poisoning. Chelation is used
to formulate nutritional supplements. Chelating agents are using in fertilizers, to prepare
homogeneous catalysts, and as contrast agents in MRI scans.

Chelate Examples

 Most biochemical molecules can dissolve metal cations to form chelate complexes.
Polynucleic acids, proteins, amino acids, polypeptides, and polysaccharides all act as
polydentate ligands.
 The bidentate ligand ethylenediamine forms a chelate complex with the copper ion to
form a five-membered CuC2N2 ring.
 Almost all metalloenzymes involve chelated metals, typically to cofactors, peptides, or
prosthetic groups.
 Hot chemical weathering is typically due to organic chelants extracting metal ions from
rocks and minerals.
 Many nutritional supplements are prepared by chelating metal ions to help protect the
metal from forming complexes with insoluble salts in the stomach. These supplements
thus provide a higher capacity for absorption.

Zwitter ion-
 “A zwitterion is a molecule that has both positive and negative regions of charge.” In the solid
state, amino acids exist as dipolar ions called zwitterions. While discussing whether a substance
is zwitterionic or not, the pH range in which the information is required must be specified
(because a sufficiently alkaline solution will change the zwitterion to an anion, and a sufficiently
acid solution will change it to a cation).
Some key Characteristics of Zwitterion are;

 They can be formed from compounds like ampholytes which contain both acid and base
groups in their molecules.
 In this type of ions, the charged atoms are usually held together by one or more covalent
bonds.
 Zwitterionic compounds have stable, separated unit electrical charges on atoms.
 These compounds contain quaternary ammonium cations.
Let us further understand the topic by looking at an example of Zwitterion.

Zwitterion Structure

Amino Acids
Amino acids are the most common example of zwitterions. They are made up of an ammonium
or amino group which contains a positive charge as well as a carboxyl group which contains a
negative charge. The zwitterion form of an amino acid is given below.

Apart from amino acids, any compound that contains acid and base centres can obtain a
Zwitterion form. Some more examples include tricine, bicine, solid sulfamic acid, alkaloids like
psilocybin amongst others.

Isoelectric Point

 Another main property of a Zwitterion is that it has an isoelectric point (represented as

pI, pH(I), IEP).
  This point is the pH value at which the charge in molecules is neutral.
 Usually, the net charge on a molecule is greatly affected by the pH of its surrounding
environment.
 In this case, molecules can become more charged (positively or negatively) as a result of
gain or loss in the number of protons.
 If we look at amino acid, the amino group is a very effective proton acceptor and the
carboxyl group is an effective proton donor.
 In addition, the solubility of a molecule at a given pH is also affected by the pI value.

Calculation of pH Value
The pH value at the isoelectric point can be calculated from the equilibrium constants (acid
and base) of the Zwitterion. It is represented by the formula;
pI=pKa1+pKa22
Where,

 pI = isoelectric point,
 Ka1 = the equilibrium constant of the acid.
 Ka2 = the equilibrium constant of the base.

Applications of Zwitterions

1. Zwitterions are widely applied in the process of separating protein molecules via SDS

PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) method which is one
of the most popular techniques used in molecular biology.
2. They also have great potential to be applied in a wide range of medical and biological
related fields.
3. Some popular uses include medical implants, drug delivery, blood contacted sensor,
separation membrane, as well as antifouling coatings of biomedical implants that help
prevent the build-up of microbial adhesion and biofilm formation.
4. In the marine industry, Zwitterionic polymers are used to prevent subaquatic organisms
from building up on boats and piers.

Drop weight method

A stalagmometer is a device for investigating surface tension using the stalagmometric method.
It is also called a stactometer or stalogometer. The device is a capillary glass tube whose middle
section is widened. The volume of a drop can be predetermined by the design of the
stalagmometer. The lower end of the tube is narrowed to force the fluid to fall out of the tube as
a drop.[2][3] In an experiment, the drops of fluid flow slowly from the tube in a vertical direction.
The drops hanging on the bottom of the tube start to fall when the volume of the drop reaches a
maximum value that is dependent on the characteristics of the solution. At this moment, the
weight of the drops is in equilibrium state with the surface tension. Based on Tate’s law:[4]
The drop falls when the weight (mg) is equal to the circumference (2πr) multiplied by the surface
tension (σ). The surface tension can be calculated provided the radius of the tube (r) and mass of
the fluid droplet (m) are known. Alternatively, since the surface tension is proportional to the
weight of the drop, the fluid of interest may be compared to a reference fluid of known surface
tension (typically water):

In the equation, m1 and σ1 represent the mass and surface tension of the reference fluid and
m2 and σ2 the mass and surface tension of the fluid of interest. If we take water as a reference
fluid,

If the surface tension of water is known which is 72 dyne/cm, we can calculate the surface
tension of the specific fluid from the equation. The more drops we weigh, the more precisely we
can calculate the surface tension from the equation. The stalagmometer must be kept clean for
meaningful readings. There are commercial tubes for stalagmometric method in three sizes: 2.5,
3.5, and 5.0 (ml). The 2.5-ml size is suitable for small volumes and low viscosity, that of 3.5 (ml)
for relatively viscous fluids, and that of 5.0 (ml) for large volumes and high viscosity. The 2.5-ml
size is suitable for most fluids.

HLB-

The hydrophilic-lipophilic balance of a surfactant is a measure of the degree to which it

is hydrophilic or lipophilic, determined by calculating values for the different regions of the
molecule, as described by Griffin in 1949[1] and 1954. Other methods have been suggested,
notably in 1957 by Davies.

Griffin's method
Griffin's method for non-ionic surfactants as described in 1954 works as follows:

HLB = Mh/M
where Mh is the molecular mass of the hydrophilic portion of the molecule, and M is the
molecular mass of the whole molecule, giving a result on a scale of 0 to 20. An HLB value of 0
corresponds to a completely lipophilic/hydrophobic molecule, and a value of 20 corresponds to a
completely hydrophilic/lipophobic molecule.
The HLB value can be used to predict the surfactant properties of a molecule:

 < 10 : Lipid-soluble (water-insoluble)

 > 10 : Water-soluble (lipid-insoluble)
 1 to 3: anti-foaming agent
 3 to 6: W/O (water in oil) emulsifier
 7 to 9: wetting and spreading agent
 13 to 16: detergent[1]
 8 to 16: O/W (oil in water) emulsifier
 16 to 18: solubiliser or hydrotrope

Protein binding:

Introduction:

The interacting molecules are generally the macromolecules such as protein, DNA or adipose. The
proteins are particularly responsible for such an interaction. The phenomenon of complex formation of
drug with protein is called as protein binding of drug. As a protein bound drug is neither metabolized
nor excreted hence it is pharmacologically inactive due to its pharmacokinetic and Pharmacodynamics
inertness. Protein + drug ⇌ Protein-drug complex.

Protein binding may be divided into

- Intracellular binding. 2. Extracellular binding.

Mechanisms of protein drug binding: Binding of drugs to proteins is generally of reversible and
irreversible. Reversible generally involves weak chemical bond such as:

1. Hydrogen bonds 2. Hydrophobic bonds 3. Ionic bonds 4. Van der Waal’s forces.

Irreversible drug binding, though rare, arises as a result of covalent binding and is often a reason for
the carcinogenicity or tissue toxicity of the drug. Absorption - As we know the conventional dosage
form follow first order kinetics. So when there is more protein binding then it disturbs the absorption
equilibrium. Distribution - A protein bound drug in particular does not cross the BBB, the placental 
barrier, the glomerulus. Thus protein binding decreases the distribution of drugs. Metabolism - Protein
binding decreases the metabolism of drugs and enhances the biological half life. Only unbound
fractions get metabolized. • e.g. Phenylbutazone and Sulfonamide. Elimination – Only the unbound
drug is capable of being eliminated. Protein binding prevent the entry of drug to the metabolizing
organ (liver) and to glomerulus filtration. • e.g. Tetracycline is eliminated mainly by glomerular filtration.
Systemic solubility of drug – Lipoprotein act as vehicle for hydrophobic drugs like steroids, heparin, oil
soluble vitamin. Drug action - Protein binding inactivates the drugs because sufficient concentration of
drug cannot be build up in the receptor site for action. • e.g. Naphthoquinone. Sustain release – The
complex of drug protein in the blood act as a reservoir and continuously supply the free drug. e.g.
Suramin sodium-protein binding for antitrypanosomal action. Diagnosis – The chlorine atom of
chloroquine replaced with radiolabeled I- 131 can be used to visualize-melanomas of eye and
disorders of thyroid gland. Factors affecting protein binding: Drug related Factor.  o Physicochemical
properties of drug Increase in lipophilicity increases the drug binding with the protein. 11 o Total
concentration of drug – Alternation in drug and protein concentration alter the drug protein binding.
Protein related Factors. o Physicochemical properties of protein – Lipoprotein bind with lipophilic
drugs. o Quantity of protein – Disease state affect the concentration of protein in blood. o Number of
binding sites – Albumin has more no of binding sites. Affinity and Magnitude of association constant. 
Drug Interaction. Displacement reaction Composition of drugs and normal body constituents.
Allosteric changes in protein molecules. Patient related factors. Age – Noenata have low albumin
content, thus less drug binding. Disease state – Disease sate alter the drug binding. Binding of drug to
blood plasma proteins – The binding of drugs to plasma proteins is reversible.  The extent or order of
binding of drug to plasma proteins is: Albumin › ὰ1-Acid glycoprotein › Lipoproteins › Globulins.
Binding of drug to human serum Albumin – It is the most abundant plasma protein (59 %). Having
M.W. of 65,000 with large drug binding capacity. Both endogenous compounds such as fatty acid,
bilirubin as well as drug bind to HSA. Four different sites on HSA for drug binding. Site I: warfarin and
azapropazone binding site. Site II: diazepam binding site. Site III: digitoxin binding site. Site IV:
tamoxifen binding site. Binding of drug to α1-Acid glycoprotein – It is called as orosomucoid.

Surfactants

surfactant, also called surface-active agent, substance such as a detergent that, when added to

a liquid, reduces its surface tension, thereby increasing its spreading and wetting properties. In
the dyeing of textiles, surfactants help the dye penetrate the fabric evenly. They are used
to disperse aqueous suspensions of insoluble dyes and perfumes.

The surface-active molecule must be partly hydrophilic (water-soluble) and

partly lipophilic (soluble in lipids, or oils). It concentrates at the interfaces between bodies or
droplets of water and those of oil, or lipids, to act as an emulsifying agent, or foaming agent.

Other surfactants that are more lipophilic and less hydrophilic may be used as defoaming agents,
or as demulsifiers. Certain surfactants are germicides, fungicides, and insecticides.

Surfactants are used in corrosion inhibition, in ore flotation, to promote oil flow in porous rocks,
and to produce aerosols.