PPAR MIDTERM WEEK 7 Raoult’s Law

COLLIGATIVE PROPERTIES ▪ The vapor pressure of a solution containing

a nonvolatile solute is lowered proportional
Physical Properties of Substances to the relative number of the solute
1. Colligative Properties – depend mainly on molecules.
the number of particles in a solution. Lowering of the Vapor Pressure
• Osmotic Pressure, Vapor Pressure
Lowering, Freezing Point ▪ According to Raoult’s Law, the vapor
Depression, Boiling Point pressure of a solvent over a dilute solution is
Elevation. equal to the vapor pressure of the pure
2. Additive Properties – depend on the total solvent, times the mole fraction of solute in
contribution of the atoms in the molecule or the solution.
on the sum of the properties of the
Determination of the Vapor Pressure of Solution
constituents in a solution.
• Molecular Weight ▪ Manometer is used and the difference of
3. Constitutive Properties – depend on the the vapor pressure between the solution and
arrangement and to a lesser extent on the the pure solvent.
number and kind of atoms within a molecule ▪ For dilute aqueous solutions, however, the
• Refractive Index, Optical Rotation, vapor pressure lowering is so slight as to
Solubility produce a serious error in the measurement.
▪ Accurate differential manometers: small
Colligative Properties
differences in vapor pressure.
o On adding a solute to a solvent, the ▪ The isopiestic method is used frequently for
properties of the solvent are modified. the precise determination of vapor pressures.

Boiling Point
▪ Vapor Pressure = decreases
▪ Freezing Point = decreases ▪ Is the temperature at which the vapor
▪ Boiling Point = increases pressure of the liquid becomes equal to the
▪ Osmosis is possible (osmotic pressure) external atmospheric pressure
These changes are called COLLIGATIVE Elevation of the Boiling Point
PROPERTIES.
▪ The boiling point of a solution of a
They depend only on the NUMBER of solute nonvolatile solute is higher than that of the
particles relative to solvent particles, not on the pure solvent, (solute lowers the vapor
KIND of solute particles. pressure of the solvent).
Vapor Pressure Determination of Boiling Point Elevation
▪ the pressure of the saturated vapor above a ▪ In the Cottrell boiling point apparatus, the
liquid resulting from the escape of the vapor and the boiling solvent are pumped by
surface liquid. the force of ebullition through a glass tube
▪ the vapor pressure of an ideal solution is and sprayed over the thermometer bulb to
dependent on the vapor pressure of each obtain an invariant equilibrium temperature.
chemical component and the mole fraction
of the component present in the solution. ▪ the phenomenon that the boiling point of a
▪ When a nonvolatile solute is combined with liquid (a solvent) will be higher when
a volatile solvent, the vapor above the another compound is added, meaning that a
solution is provided solely by the solvent solution has a higher boiling point than a
▪ The solute reduces the escaping tendency of pure solvent.
the solvent, and, on the basis of Raoult’s ▪ This happens whenever a nonvolatile solute,
Law. such as a salt, is added to a pure solvent,
such as water.
▪ The boiling point can be measured
accurately using an ebullioscope.
Freezing Point Change in Freezing Point

▪ the phenomenon in which the freezing point

of a liquid (a solvent) is depressed when
another compound is added, meaning that a
solution has a lower freezing point than a
pure solvent.
▪ This happens whenever a nonvolatile solute
is added to a pure solvent, such as water.
▪ The phenomenon may be observed in sea
water, which due to its salt content remains The freezing point of a solution is LOWER than that
liquid at temperatures below 0°C (32°F), the of the pure solvent
freezing point of pure water.
▪ The triple point of air-free water, at which
solid, liquid, and vapor are in equilibrium,
lies at a pressure of 4.58 mm Hg and a
temperature of 0.0098 °C.
▪ If a solute is dissolved in the liquid at the
triple point, the escaping tendency or vapor
pressure of the liquid solvent is lowered
below that of pure solid solvent.
▪ The temperature must drop in order to
reestablish equilibrium between the liquid
and the solid.

Methods for the Determination of Freezing Point Osmotic Pressure

Lowering ▪ the pressure which needs to be applied to a
1. Beckmann method solution to prevent the inward flow of water
▪ It consists of a jacketed tube with a across a semipermeable membrane.
sidearm through which the test ▪ The phenomenon of osmotic pressure arises
material may be introduced. A from the tendency of a pure solvent to move
Beckmann thermometer is through a semi-permeable membrane and
supported in the tube and extends into a solution containing a solute to which
into the test solution. the membrane is impermeable.
▪ A glass stirrer passes through a ▪ All aqueous solutions of non-volatile solutes
tube in the stopper and is operated exert an osmotic pressure.
manually or by means of a motor. ▪ Osmosis is the diffusion of solvent through
▪ The tube and jacket are supported a semi-permeable membrane that allows
in a vessel containing mixture of only solvent to move through it.
salt and ice. ▪ Osmotic Potential is the opposite of water
▪ In carrying out a determination, the potential, which is the degree to which a
temperature is read on the solvent tends to stay in a liquid.
Beckmann differential thermometer ▪ Osmotic Pressure Osmometer is based on
at the freezing point of the pure the principle of thistle tube.
solvent, water. Van’t Hoff Equation
▪ A known weight of the solute is
introduced into the apparatus, ▪ ¶V= Nrt or ¶=mRT
containing a given weight of ▪ Where:
solvent, and the freezing point of ¶ is the osmotic pressure in atm
the solution is read and recorded. V is the volume of solutions in Liters
2. The Equilibrium method. n is the number of moles of solute
R is the gas constant equal to 0.082L
atm/mole
T is the absolute temperature
▪ Van’t Hoff concluded that there was an
apparent analogy between solutions and
gases and that the osmotic pressure in a
dilute solution was equal to the pressure that
the solute would exert if it were a gas
occupying volume.
▪ Corresponded to the equation for ideal gas.
▪ Morse Equation ¶= RTM

▪ Osmotic pressure is an important factor

affecting cells. Osmoregulation is the
homeostasis mechanism of an organism to
reach balance in osmotic pressure.
▪ Hypertonicity is the presence of a solution
that causes cells to shrink.
▪ Hypotonicity is the presence of a solution
that causes cells to swell.
▪ Isotonic is the presence of a solution that
produces no change in cell volume.
 PPAR 211: ACID AND BASE EQUILIBRIA • Weak bases only partially dissolve into ions
in solution
Three Main Classifications of Acid and Bases
Example:

Mg (OH)2 (aq) Mg2+ (aq) + 2 OH- (aq)

NH3 (aq) + H2O(l) NH4+ (aq) + OH- (aq)

Conjugate Acid-Base Pairs

Conjugate Acid

• Base that accepts proton

The pH Scale • Salt of weak base and strong acid

• The acidity of a substance can be NH3 + H2O NH4 + OH-

determined by measuring the concentration based conjugate

by hydronium H3O+ (or H+) in solution. base

• pH is related to the concentration of

hydronium H3O+ Conjugate Base
• pH = - log [H3O+]
• Acid that donated a proton
• Salt of weak acid and strong base

acid base HCl + H2O H3O+ + Cl-

0 7 14 acid conjugate base

HF + H2O H3O+ + F-
acid conjugate base

• the lower the pH, the more acidic the

solution Neutralization Reaction
• the higher the pH, the more basic
• Acid and base react to form water and salt
• HCL + NaOH H2O + NaCl
acid base water salt
Strong vs. Weak Acids • HF + NH3 H2O + NH4F
acid base water salt
• HCl is a strong acid

HCl (aq) + H2O (l) H3O+ (aq) + Cl- (aq) BUFFERS

• HF is a weak acid
• Compounds or mixtures of compound that
HF (aq) + H2O (l) + -
H3O (aq) + F (aq) by their presence in the solution resist
changes in the pH upon the addition of small
Strong and Weak Bases quantities of acid or alkali

• Bases can be categorized in exactly the same Types of Buffers

way.
• Strong bases dissolve completely into ions • Acidic Buffers
in solution ▪ Combination of weak acid and
conjugate base
Example:
▪ Examples:
NaOH (aq) Na+ (aq) + OH- (aq) • CH3COOH CH3COONa
• H2CO3 NaHCO3
• H3PO4 NaH2PO4
• HCOOH HCOONa
 CH3COOH + NaOH CH3COOna + H2O • HPO4-2 – conjugate base + hydronium
acid base salt (CB) water
KH2PO4 K+ + H2PO4 Na+ + OH- NaOH

• Basic Buffer HPO42- + H2O

▪ Combination of weak acid and
K2HPO4 K+ + HPO42- H+ + Cl- HCl
conjugate base
▪ Examples: H2PO4
• NH4OH NH4Cl
• NH3 NH4Cl
• NH3 (NH4)2CO2 BUFFER EQUATION

NH3 + HCl + H2O NH4Cl + H2O (Henderson – Hasselbalch Equations)

• Used to know pH of buffer solutions

• Phosphate Buffer
• Helps in calculating the pH value of buffer
▪ aka double salt buffer
▪ third buffer system solution, is the concentrations of acids as
▪ composed of two (2) salt well as that of the salts are known
• monobasic potassium phosphate Acid – Dissociation Constant (Derivation)
(KH2PO4)
• dibasic potassium phosphate (K2H HA = H + A [𝐻𝐴]
acid H ion (salt)
PO4) 𝑝ℎ = − log 𝑘𝑎 + 𝑙𝑜𝑔
[𝐴]
[HA] = [H ] + [A ]
Buffer Action 𝑘𝑎 =
[𝐻 ][𝐴 ]
[𝐴] − 𝑠𝑎𝑙𝑡
[𝐻𝐴] 𝑝ℎ = pka + log
[𝐻𝐴] − 𝑎𝑐𝑖𝑑
[𝐻𝐴]
• resistance of a buffer solution to a change in [H ] = ka
[𝐴]
pH
[𝐻𝐴]
− 𝑙𝑜𝑔 [𝐻 ] = − log
Mechanism of Action of Acidic Buffers [𝐴]

CH3COONa CH3COO- + Na+ H+ + Cl- HCl

CB acid FORMULAS & CONCEPTS
CH3COOH
Acid Base

CH3COOH CH3COO- + H+ OH- + Na+ NaOH 𝑝𝐻 = − log [𝐻 ] 𝑝𝑂𝐻 = − log [𝑂𝐻 ]

WA base
− log[H O ]

H2O [𝐻 ][𝐴 ] [𝑂𝐻 ][𝐵 ]

𝑘𝑎 = 𝑘𝑏 =
[𝐻𝐴] [𝐵𝑂𝐻]
• it turns into another compound which is why
pH is not affected 𝑝𝐾𝑎 = − log 𝑘𝑎 𝑝𝐾𝑏 = − log 𝑘𝑏

Mechanism of Action of Basic Buffers

[𝐴 ] − 𝑠𝑎𝑙𝑡 [𝐵 ] − 𝑠𝑎𝑙𝑡
𝑝𝐻 = pKa + log 𝑝𝑂𝐻 = pKb + log
NH4OH NH4+ + OH- H+ + Cl HCl [𝐻𝐴] − 𝑎𝑐𝑖𝑑 [𝑂𝐻] − 𝑏𝑎𝑠𝑒
WB acid

H2O [H ] = pH = pOH = acidic [OH ] = pOH = pH = basic

NH4Cl Cl + NH4 OH- + Na NaOH

CA base

BUFFER CAPACITY
NH4OH
• measure of its magnitude of its resistance to
• instead of raising pH, it resist the change change in the pH on an addition of acid or
with buffers and throw it to another base
compound • aka buffer index, buffer value, buffer
Mechanism of Action of Phosphate Buffers efficiency, or buffer coefficient
• represented by β
• H2PO4 – weak acid + hydroxyl
 ▪ ratio of increment of strong acid/base to
small change in pH brought by this
addition
AA AB
• β= or β =
pH pH

APPLICATIONS

• Biological – pH is blood is maintained at 7.4 by

two buffer system.
• Primary Buffer
▪ Present in plasma
▪ Contains carbonic acid / carbonate /
acid / alkali sodium salt of phosphoric
acid
• Second Primary
▪ Present in erythrocytes
▪ Oxy-haemoglobin / haemoglobin ; acid
/ alkali potassium salts of phosphoric
acid
• Pharmaceutical – buffers as an ingredients to
adjust the pH of the product to that required for
maximum stability.
• Parenteral Solution (injections)
▪ Ideal pH is 7.4
▪ Most commonly used buffers are
acetate, phosphate, citrate, and
glutamate
• Ophthalmic Preparation
▪ Maintain pH within physiological pH
range of lacrimal fluid
• 7-8 pH
▪ Has good buffering capacity and can
tolerate 3.5 – 10.5 pH with little
discomfort
▪ Most commonly used buffers are
borate, carbonate, and phosphate.
• Ointments and Creams
▪ Most commonly used buffer are citric
acid / its salts and phosphoric acid / its
salt
 PPAR 211: COMPLEXATION LIGANDS

Complexes: interaction between metal + electron • A group, ion, or molecule coordinated to a

donating compound central atom or molecule in a complex.
• This donate a pair of electrons in forming a
• Metal
complex with metal ion.
▪ Electron receiver
▪ Lewis acid CHELATING AGENTS
▪ Cation (+)
• Electron • A substance whose molecules can form
▪ Ligand several bonds to a single metal iob.
• Electron donor • EXAMPLE : ethylenediamine
• Lewis base chelate with two ethylenediamine ligands
• Anion (-)
❖ Polydentate ligand – 2 or more binding site
❖ Monodentate ligand – 1 binding site

• If metal ion react with monodentate ligand =

complex
• If metal ion react with polydentate ligand =
chelates

Metal + ligand = complex

Metal + chelating agent = chelate Ethylenediaminetetraacetic acid (EDTA) –

both surrounded by an anion Polydentate (6 – hexadentate)

Ligand – coordinated to central atoms • This is a versatile chelating agent. It can form
four or six bonds with a metal ion, and it forms
Chelating agent – can form several bonds to central chelates with both transition-metal ions and main
atom group ions.
• EDTA is frequently used in soaps and
CHELATES
detergents, because it forms a complexes with
• A substance containing two or more donor calcium and magnesium ions.
groups which combine with a metal
• A compound having a ring structure that • All ligands are lone pair donors. In other words,
usually contains a metal ion held by all ligands function as Lewis bases
coordinate bonds. • “Chelation” derived from the Greek chele,
• Chemically, a chelate is a compound from lobster’s claw
complexing of cations with organic • Relates to the interaction between a metal atom
compounds resulting in a ring structure. or ion and another species, known as Ligand, by
• Typical structure of chelates with known which heteroatomic ring is formed
organic acids: citric acid, tartaric acid, • Chelation changes the physical and chemical
gluconic acid and glycine. characteristics of the metal ion and the ligand.
• It is simplest to consider the ligand as the
electron pair donor and the metal as the electron
pair acceptor, with the donation establishing a
coordinated bond
• Many chelating agents act in the form of anions
which coordinate to a metal ion
• For chelation to occur, there must be at least two
donor atoms capable of binding to the same
metal ion, and ring formation must be sterically
possible
• When a drug forms a metal chelate (heavy metal
+ chelating agent), the solubility and absorption
of both drug and metal ion may be affected, and
 drug chelation may either increased or decreased between two or more different chemical
absorption constituents
• Intermolecular forces involved in the formation
Inorganic Complex
of complexes are the van der Waals forces of
• 6 Ammonia group in Hexamminecobalt (III) dispersion, dipolar, and induced dipolar types.
chloride. Hydrogen bonding provides a significant force in
some molecular complexes, and coordinates
Organic Complex covalence is important in metal complexes.

• Dimethylaniline and 2,4,6 trinitroanisole Classification of Complexes

Naturally Occuring Chelates (multiple bond) • Metal Ion Complexes

• Organic Complexes
• Chlorophyll (magnesium) and Hgb (iron)
• Inclusion Compound
Therapeutic chelators

• are used in syndromes where there is metal ion Is based upon familiarity with atomic structure and
overload. molecular forces.
• Example: WALA DITO PAGE 29-31 (ppt)
• EDTA as monocalcium disodium salt is
used in the tx of lead poisoning (Ca averts • An aromatic hydrocarbon or arene (or
the problems of calcium depletion) sometimes aryl hydrocarbon) is a
• Deferiprone chelates iron hydrocarbon characterized by general
• Tetracycline chelation alternating double and single.
▪ Tetracycline + Chloroquine
Aromatic type: Complexes of π–bonded and
• Doxycycline: DOC for
aromatic ligands
leptospirosis
Do not drink milk – calcium (metal
ion) (will not absorb)

• Polyvalent cations such as Fe+2 and Mg+2 and

anions such as trichloroacetate or phosphate
interfere with absorption of both model and real
systems
• Ferrous sulfate (iron) has the greatest inhibitory
effect on tetracycline absorption
• The antibacterial action of the tetracyclines
depends on their metal-binding activity, as their Classes of Complexes (interaction between metal
main site of action is on the ribosomes, which ion and ligand)
are rich in magnesium (can be found in
1. Metal Complexes
ribosomes of bacteria)
2. Organic Complexes
• Tetracyclines readily form complexes with
3. Inclusion Compounds
divalent metals, but they have a greater affinity
for the trivalent metals with which they form 3:1 Covalent Bonds
drug–metal chelates.
• Therapeutically active tetracyclines form 2:1 A ----------- B (primary covalent bond)
complexes with cupric, nickel and zinc ions C : -------- : D (coordinate bond – electron came
while inactive analogues form only 1:1 from single atom)
complexes
Metal complex ion
COMPLEXATION AND PROTEIN BINDING
• A complex ion has a metal ion at its centre
• Complexes (coordinate bond between metal and with a number of other molecules or ions
ligand) or coordination compounds, according to surrounding it. These can be considered to
the classic definition, result from a donor- be attached to the central ion by coordinate
acceptor mechanism or Lewis acid-base reaction bonds.
 • (In some cases, the bonding is actually more • A sort hollow ring of carbon and hydrogen
complicated than that.) atoms, at the centre of which are 4 nitrogen
• Metal ion complexation is based upon a atoms with lone pairs on them.
familiarity with atomic structure and ❖ The functional part of this is an iron(II) ion
molecular forces, surrounded by a complicated molecule called
• Inorganic Complexes. haem (heme). This is a sort of hollow ring of
▪ This group constitutes the simple carbon and hydrogen atoms, at the centre of
inorganic complexes first described by which are 4 nitrogen atoms with lone pairs on
Werner in 1891 (chemical bond of them.
compound is generated due to complex ❖ A quadridentate ligand
ions interaction). ❖ Haem is one of a group of similar compounds
• The ammonia molecules in called porphyrins
hexamminecobalt III chloride, as the ❖ Each of the lone pairs on the nitrogen can form a
compound [Co(NH3)6]3+Cl3- is called, are co-ordinate bond with the iron(II) ion - holding it
known as the ligands and are said to be at the centre of the complicated ring of atoms.
coordinated to the cobalt ion.
EDTA
• The coordination number of the cobalt ion,
or number of ammonia groups coordinated ❖ A hexadentate ligand (magnesium)
to the metal ion is six. ❖ A hexadentate ligand has 6 lone pairs of
electrons - all of which can form coordinate
Chelates
bonds with the same metal ion. The best example
• Some of the bonds of the chelate may be is EDTA.
ionic or of the primary covalent type, while ❖ EDTA is used as a negative ion - EDTA4-.
others are coordinate covalent links. ❖ Albumin
• Monodentate • Can bind 2 metals; Cu & Ni
▪ When the ligand provides one group for • is the main carrier of various metal ions and
attachment to the central ion small molecules in the blood serum. The N-
▪ Pilocarpine behaves as a monodentate terminal portion of human serum albumin
ligand toward Co (II), Ni(II), and Zn(II) binds Cu(II) and Ni(II) with higher affinity
to form chelates of pseudotetrahedral than that of dog serum albumin.
geometry.
ORGANIC MOLECULAR COMPLEXES
• The donor atom of the ligands is the
pyridine-type nitrogen of the imidazole of • An organic coordination compound or
pilocarpine. (complex) molecular complex consists of constituents
• Molecules with two and three donor groups held together by weak forces of the donor-
are called bidentate and tridentate, aceptor type or by hydrogen bonds.
respectively • Not common (metal)
• Chlorophyll and hemoglobin, two extremely ❖ The compounds, dimethylaniline and 2,4,6-
important compounds, are naturally trinitroanisole, react in the cold to give a
occurring chelates involved in the life molecular complex.
processes of plants and animals.
• Chlorophyll and hemoglobin, two extremely
important compounds, are naturally When they react with cold; low
occurring chelates involved in the life temp they form molecular
processes of plants and animals. complex
HEMOGLOBIN

❖ RON(II)- is the functional part surrounded by a

complicated molecule called haem (heme) *4
binding site*
❖ haem (heme) Non covalent bond
• Is one of a group of similar compounds—
Porphyrins
❖
❖ On the other hand, these two compounds react at Polymer Complexes
an elevated temperature to yield a salt (primary
covalent bond), the constituent molecules of ❖ Polyethylene glycols, polystyrene,
which are held together by primary valence carboxymethylcellulose, and similar polymers
bonds. containing nucleophilic oxygens can form
complexes with various drugs.
Quinhydrone Complexes
Other types of complex
❖ Mixing alcoholic solutions of equimolar
quantities of benzoquinone and hydroquinone ❖ Molecular complexes of many types may be
forms the molecular complex quinhydrone observed in systems containing two or more drug
molecules:
Picric Acid Complexes (pKa) ❖ Generally, association follows from attractive
interactions (hydrophobic, electrostatic or charge
❖ Picric acid, 2,4,6-trinitrophenol, pka = 0.38, transfer interactions) between two molecules
reacts with strong bases to form salts and with
weak bases to form molecular complexes. ❖ The imidazole moiety is involved in many
❖ Butesin picrate (Abbott Laboratories), interactions.
presumably a 2:1 complex. ❖ For example, caffeine and theophylline are
Drug Complexes frequently implicated in interactions with
aromatic species.
❖ The interaction between caffeine and a drug such ❖ Caffeine increases the solubility of ergotamine
as sulfonamide or a barbiturate has been and benzoic acid.
attributed to a dipoledipole force or hydrogen
bonding between the polarized carbonyl groups
of caffeine and the hydrogen atom of the acid.

Hydrophobic interaction

❖ Large hydrophobic species such as proteins

avoid the water molecules in an aqueous solution
in so far as possible by associating into micelle-
like structures with the nonpolar portions in
contact in the inner regions of the “micelle” the
polar ends facing the water molecules.
❖ This attraction of hydrophobic species, resulting
from their unwelcome reception in water, is
known as hydrophobic bonding, or better
hydrophobic interaction.
❖ It involves van de Waals forces, hydrogen
bonding of water molecules in a three
dimensional structure, and other interactions.
INCLUSION COMPOUNDS

❖ The class of addition compounds known as

inclusion or occlusion compounds results more
from the architecture of molecules than from
Hydrophobic their chemical affinity.
Interaction
❖ The class of addition compounds

• Chemical Lattice type

• Layer type
• Clathrates
Chemical lattice type

• The choleric acids (bile acids) can form a Clathrates

group of complexes principally involving
deoxycholic acid in combination with • The clathrates crystallize in the form of a
parrafins, organic acids, esters, ketones, and cage-like lattice in which the coordinating
aromatic compounds and with solvents compound is entrapped. Chemical bonds are
not involved in these complexes, and only
• The crystals of deoxycholic acid are
the molecular size of the encaged
arranged to form a channel into which the
component is of importance.
complexing molecule can fit.
• The incompatibilities of certain polyethers,
• Colestyramine and colestipol
such as the Carbowaxes, Pluronics and
▪ insoluble quaternary ammonium anion
Tweens with tannic acid, salicylic acid, and
exchange resins which, when
phenol, can be attributed to these
administered orally, bind bile acids and
interactions
increase their elimination because the
high-molecular-weight complex is not • One official drug, warfarin sodium USP, is a
absorbed. clathrate of water, isopropyl alcohol, and
sodium warfarin in the form of a white
• As bile acids are converted in vivo into
crystalline powder
cholesterol, colestyramine is used as a
hypocholesteraemic agent. Bile acid COUMADIN (crystalline warfarin sodium)
• Bile acid cholesterol
• When given to patients receiving other drugs
Form inclusion compounds
as well, the resin would conceivably bind
anionic compounds and reduce their
absorption.
• Decreased drug absorption
▪ can be caused by use of colestyramine
or colestipol and has been reported, for
example, with thyroxine, aspirin,
phenprocoumon, warfarin,
chlorothiazide, cardiac glycosides and Monomolecular Inclusion Compounds
ferrous sulfate
• Other examples: • Cyclodextrins. In addition to channeland
▪ Urea and thiourea, starch Iodine cage-type (clathrate) compounds, these
added the mono- and macromolecular
Layer Type inclusion compounds.
• Monomolecular inclusion compounds
• Some compounds such as clay
involve the entrapment of a single guest
montmorillonite, the principal constituent of
molecule in the cavity of one host molecule.
bentonite, can trap hydrocarbons, alcohols,
Monomolecular host structure is represented
and glycols between the layers of their
by the cyclodextrins. > carbohydrates
lattices.
• These compounds are cyclic
• Graphite can also intercalate compounds
oligosaccharides
between its layers.
• Their ability to form inclusion compounds in
aqueous solution is due to the typical
arrangement of the glucose units

Cyclodextrin

• are studied as solubilizing and’ stabilizing

agents in pharmaceutical dosage forms.
➢ Inclusion compounds • The cyclodextrin is used to solubilize
sulfonamides, tetracyclines, morphine,
aspirin, benzocaine, ephedrine, reserpine,
and testosterone.
EXAMPLE OF INCLUSION FORMATION • this protein appears to have a greater affinity
for basic than for acidic drug molecules
• In cases where drug is highly protein bound
(around 90%), small changes in binding lead
Cage – trap molecule to drastic changes in the levels of free drug
host molecule in the body. Protein bound
• Both ampicillin (50/mg/kg every 2 h) and
oxacillin (50 mg/kg/h) produce similar peak
levels in the serum given as repeated
intravenous boluses.
• Levels of free drug are markedly different,
Inclusion however, as oxacillin is 75% protein bound
compound • and ampicillin is 17.5% bound

Binding to plasma proteins

• Most drugs bind to a limited number of sites

on the albumin molecule.
Molecular Sieves (separate) • Plasma proteins other than albumin may
also be involved in binding.
• Macromolecular inclusion compounds • Blood plasma normally contains on average
include zeolites, dextrins, silica gels, and about 6.72 g of protein per 100 cm3; the
related substances. protein comprises 4.0 g of albumin, 2.3 g of
• The atoms are arranged in three dimensions globulins and 0.24 g of fibrinogen.
to produce and channels. • Dicoumarol binds to β- and γglobulins, and
• Synthetic zeolites may be made to’ a certain steroid
definite pore size so as to separate molecules • hormones are specifically and preferentially
of different dimensions, and they are also bound to particular globulin fractions
capable of ion exchange.
Lipophilicity and protein binding
PROTEIN BINDING
• Muscle protein may bind drugs such as
Unbond – active digoxin and so act as a depot. > storage
• Dicloxacillin, which is 95% bound to
Bound – inactive > stay in bloodstream
protein, is absorbed more slowly from
• The binding of drugs to proteins contained muscle than ampicillin, which is only bound
in the body can influence their action in a to the extent of 20%.
number of ways. Proteins may • Protein binding can affect antibiotic
1. facilitate the distribution of drugs action.
throughout the body, ▪ For example:
2. inactivate the drug by not enabling • Penicillins and cephalosporins bind
a sufficient concentration of free drug reversibly to albumin.
to • Only the free antibiotic has
3. retard the excretion of a drug. antibacterial activity
• The interaction of a drug with proteins may Protein bound – weak bound/bind > reversible
cause • Warfarin, anticoagulant, serves as a model
▪ displacement of body hormones or a drug in protein binding studies because it is
coadministered agent, extensively but weakly bound.
▪ a configurational change in the protein, ▪ Thus, many drugs are able to compete
the structurally altered from which is with and displaced warfarin into its
capable of binding a coadministered binding sites
agent, or the formation of a drug-protein • Warfarin also can be displaced by
complex that itself is biologically active nonsteroidal antiinflammatory drugs
• alpha1-acid glycoprotein, has been shown to (NSAIDS).
bind numerous drugs;
Indicate which of the following statements relating to
the formation of chelates are true:

1. Chelation (organic/molecular) is the

interaction between a large organic anion
and organic cation. False
2. Chelation is the interaction between a metal
ion and a ligand. True
3. The ligand is the electron pair acceptor
(donor). False
4. Chelation results in the formation of a
heteroatomic ring. True
5. Tetracyclines forms 3:1 drug-metal chelates
with magnesium ions. True

Indicate which of the following statements relating to

the protein binding of drugs are true:

1. Protein binding to plasma albumin is a

reversible process. True
2. Protein binding decreases the free drug
concentration. True
3. Drugs with a low lipophilicity have a high
degree of protein (lipophilic) binding. False
4. Protein (Effect) binding of antibiotics
usually increases antibiotic action. False
 PPAR

Solubility and Distribution Phenomena SOLUBILITY PROCESS

Solubility mechanistic perspective of solubilization process for

organic solute in water involve the following steps:
• quantitative terms as the concentration of
solute in a saturated solution at a certain 1. break up of solute- solute intermolecular
temperature. bond
• measure of ability of a solute to get dissolve
in a solvent 2. Break up if solvent intermolecular bond

Qualitative solubility – defined as the spontaneous

interaction of two or more substances to form 3. Formation of cavity in solvent phase large
homogenous molecular dispersion. enough to accommodate solute molecule
Thermodynamic solubility of drugs – maximum
4. transfer of solute into the cavity of solvent
amount of the most stable crystalline form that
phase
remains in solution in a given volume of the solvent
at a given temperature and pressure under
equilibrium conditions.
5. formation of solute-solvent intermolecular
Solution – defined as a chemically and physically bond
homogenous mixture of two or more substances
EQUILIBRIUM – BALANCE OF ENERGY OF 3
Components of Solution: INTERACTIONS AGAINST EACH OTHER.

• Solute – dissolving substance 1. Solvent with solvent

• Solvent- dissolving medium 2. Solute with solvent
3. Solvent with solute
Degree of Saturation
• ETHALPHY is released it absorbed during the
• Saturated Solution dissolving process (constant pressure)
▪ one in which solute in solution us in
equilibrium with the solid phase Positive enthalpy – endothermic reaction
▪ contains the max amount of solute Negative enthalpy – exothermic reaction
dissolved in a solvent
USP Terms of Solubility
▪ Q = KSP
• Unsaturated or Subsaturated Solution
▪ one containing the dissolved solute in a
conc below the necessary for complete
saturation at a definite temperature
▪ solution contains less than the amt. of
solute.
▪ Q < KSP
• Supersaturated Solution
▪ one that contains more of the dissolved
solute that it would normally contain at
a definite temperature, were the BIOPHARMACEUTICS CLASSIFICATION
undissolved solute present. SYSTEM (BCS)
▪ Solution contain more than the amount
• is the scientific framework for classifying drug
of solute dissolved in a solution.
subsatnces accoirding to their aquoes solubility
▪ Q > KSP
ad their intestinal permeability
 NONPOLAR SOLVENT

• Ionic and polar solutes ate not soluble or are only

slightly soluble in NP solvents
• NP solute are soluble in NP solvents
• eg. Oil and fats dissolves carbon tetrachloride,
benzene and mineral oil
• alkaloid bases and fatty acids dissolves in NP
solvents

SEMIPOLAR SOLVENTS

• induced polarity in nonpolar solvents

• Eg: ketones alcohol _induce polarity in NP
Class I – these drugs are rapidly absorbed and have (benzene)
high bioavailability • Acts as intermediate solvents – bring about
ex. metoprolol, paracetamol miscibility of polar and nonpolar liquids
• Acetone increase solubility of ether in water.
Class II – Absorption rate drugs is limited by • Alcohol – mineral oil/castor oil and water
dissolution rate • Propylene glycol – increase solubility of water
ex. glibenclamide, bicalutamide, griseofulvin, and peppermint oil and water and benzyl
ezetimibe benzoate
Class III – absorption of these drugs is limited by SOLUBILITY OF LIQUIDS IN LIQUIDS
their permeability across the intestinal epithelium
ex. cimetidine, acyclovir • Hydroalcoholic – water +alcohol
• Aromatic water – volatile oil + water
Class IV – these drugs have both low permeability • Spirits and elixir – volatile oil +alcohol
and low solubility making their absorption
• Collodion- ether and alcohol
challenging
• Lotion, sprays and ,medicated oil – combination
ex. bifonazole, furosemide
of fixed oils
SOLVENT-SOLUTE INTERACTION • Miscibility- refers to the mutual solubilities of
the components in liquid-liquid system
• “LIKE DISSOLVES LIKE” – main principle • Two categories:
Polar solvents • Complete miscibility
• Polar and semipolar such as water and alcohol
• Dissolves ionic solute and other polar substances glycerin and alcohol and alcohol acetone
• Water dissolves phenol, alcohol, aldehydes, • NP benzene and carbon tetrachloride
ketone and other oxygen and nitrogen containing • Oleic acid is insoluble in water but soluble in
compounds that can form hydrogen bonds with alcohol and ether
water • Tartaric and citric acid are soluble in water
• Potassium and ammonium bitartrates are not
• As the length of a non- polar chain of an very soluble in water
aliphatic alcohol increases the solubility of the • ASA is water insoluble bur sodium citrate is
compound in water decreases used to dissolve it in water
• Addition of polar group are present in the • Benzoic acid soluble in sodium hydroxide
molecules as found in propylene glycol, glycerin solution, alcohol and fixed oils.
and tartaric acid water solubility increase greatly. • Salicylic acid is soluble in alkalies and in alcohol
Branching of carbon chain reduces the NP effect • Phenol is weakly acidic and only slightly soluble
and leads to increase water solubility in water but is quite soluble in diluted sodium
• Example tertiary butyl alcohol compare to n- hydroxide solution
butyl alcohol. • Most weak electrolytes are not very soluble in
water but are soluble in dilute solution of acids
SOLUTE SOLVENT INTERACTIONS

• A-SOLVENT • NATURE OF SOLUTE AND SOLVET

• B-SOLUTE • PARTICLE SIZE
• MOLECULAR SIZE
• AA>>A-B solvent molecules will be attracted to ▪ Larger the molecule or the higher the MW
each others and the solute will be excluded the less soluble the substance
• Benzene and water, benzene molecules unable to ▪ Organic compounds – the amount of carbon
penetrate closelu bound water aggregates branching will increase the solubility since
more branching will reduce the size or
• BB>>AA solvent will not be able to break the volume of the molecules and make it easier
binding forces between solute molecules to solvate the molecules with solvent
• NaCl in benzene, where NaCl crystas is held by
strog elctrovalent forces which cannot be broken
by benzene

• AB>>AA or BB three forces are equal – Solute

will form a solution eg NaCl in water

CLASSIFICATION OF SOLVENT AND THEIR • BOILING POINT AND MELTING POINT

MECHANISM OF ACTION ▪ Aqueous solubility decreases with
increasing BP and MP
1. Polar solvents
2. Non-polar solvents
3. Semi-polar solvents

TYPES OF SOLUTION
• INFLUENCE OF SUBSTITUENTS
• GAS IN LIQUIDS
▪ When pressure above the solution is released ▪ HYDROPHYLIC OR HYDROPHOBIC
(decreases) the solubility of gas decreases
▪ As the temperature increases the solubility
of gases decreases
• LIQUIDS IN LIQUIDS
▪ Complete miscibility – alcohol and water,
glycerin and alcohol, benzene and carbon
tetrachloride
▪ Partial miscibility – phenol water, two
liquid layers are formed each containing
some of the other liquid in the dissolved
state
• SOLID AND LIQUIDS

FACTORS INFLUENCING SOLUBILITY

• PARTICLE SIZE SURFACE AREA OF DRUG

 PPAR 211: Interfacial Phenomena Insects walking on water

two phases • Several insects are able to walk on water,

such as the water strider.
• When phases exist together, the boundary • Their legs are formed to distribute their
between two of them is termed an interface. weight, causing the surface of the liquid to
• the bulk of each phase that they are referred become depressed, minimizing the
to as forming is “interfacial phase” potential energy to create a balance of
• INTERFACE: 1. Liquid Interface forces so that the strider can move across
SURFACE: Gas – Solid and Gas -Liq the surface of the water without breaking
through the surface.
The solid-solid interfaces have practical significance
in pharmacy practice • This is similar in concept to wearing snow
shoes to walk across deep snowdrifts
Example without your feet sinking.
• These specialized non-wetting legs and feet
• adhesion between granules along with extremely low body weight
• preparation of layered tablets facilitate the strider's ability to live on the
• flow of particles surface of water without sinking.
Surface and Interfacial Tensions • It allows small metal objects such as
needles, razor blades, or foil fragments to
• Surface tension – force that pull the float on the surface of water, and causes
molecules of the interface together resulting capillary action.
to contract the surface. Capillaliry / wicking – upward movement
• The liquid droplets tend to assume a of solvent against the gravity
spherical shape, since a sphere has the Paper Chromatography – used to separate
smallest surface area per unit volume. pigments in a component (due to capillary
• Force = mass x acceleration action)

▪ This “tension” of surface, is the force ❖ At the surface of the liquid, the molecules are
per unit length that must be applied pulled inwards by other molecules deeper
parallel to the surface so as to inside the liquid but they are not attracted as
counterbalance the net inward pull. intensely by the molecules in the neighboring
▪ This force, the surface tension, has the medium (be it vacuum, air or another liquid).
units of dyne/cm in the cgs system.

• Interfacial Tension - the force per unit

length existing at the interface between two
immiscible liquid phases

▪ In physics, surface tension is an effect

within the surface layer of a liquid that
causes that layer to behave as an elastic
sheet. Examples of Surface Tension
▪ This effect allows insects (such as the
❖ Drops of water
water strider) to walk on water.
• When using a water dropper, the water does
❖ The water strider relies on the surface tension of not flow in a continuous stream, but rather
water to skate about on the surface of streams in a series of drops.
and ponds without sinking. • The shape of the drops is caused by the
❖ The relatively high surface tension of water surface tension of the water. The only
allows its surface to behave like a film. The reason the drop of water isn't completely
surface depresses slightly under the waxy pad- spherical is because of the force of gravity
like feet which are covered with tiny hairs pulling down on it.

❖ In the absence of gravity, the drop would

minimize the surface area in order to minimize
 tension, which would result in a perfectly ❖ The surface of the skin is bathed in an aqueous-
spherical shape oily layer having a polar-nonpolar character
similar to that of a mixture of fatty acids.
• Needle (or paper clip) floating on water. ❖ For a lotion with a mineral oil base to spread
▪ Even though the density of these objects freely and evenly on the skin, its polarity and
are greater than water, the surface hence its spreading coefficients should be
tension along the depression is enough increased by the addition of a surfactant.
to counteract the force of gravity ❖ The relation between spreading, HLB
pulling down on the metal object. (hydrophile-lipophile balance), and emulsion
stability has been added.
The Cause of Surface Tension ❖ Surfactant blends of varying HLBs were added
❖ Surface tension is caused by the attraction to oil, a drop of which was then placed on water
between the molecules of the liquid by various
intermolecular forces.
❖ In the bulk of the liquid each molecule is pulled
equally in all directions by neighboring liquid
molecules, resulting in a net force of zero.
❖ Ordinarily, interfacial tensions are less than
surface tensions because the adhesive forces
between two liquid phases forming an interface
are greater than when a liquid and a gas phase
exist together.
❖ It follows that if two liquids are completely
miscible, no interfacial tension exists between Surface-Active Agents
them.
❖ It is important to consider the types of molecular ❖ Surface-active agents or surfactants are the
structures that lead to high spreading molecules and ions that are adsorbed at
coefficients. interfaces.
❖ Oil spreads over water because it contains polar ❖ also known as Amphiphile, which the molecule
groups such as COOH or OH. Hence, propionic or ion has the affinity for both polar and
acid and ethyl alcohol should have high values of nonpolar solvents.
S. ❖ Depending on the number and nature of the polar
and nonpolar groups present, the amphiphile
As the carbon chain of an acid, oleic acid for may be predominantly hydrophilic (water-
example, increases, the ratio of polar-nonpolar loving), lipophilic (oil-loving), or reasonably
character decreases and the spreading coefficient on well balanced between these two extremes.
water decreases.
An increase in the length of the ethylene oxide chain
Surfactants / Surface active agent of polyoxyethylated non-ionic surfactant result in
decreased surface activity
• “amphiphiles” – polar/nonpolar
Micelles
Hydrophilic
(contact w/ water)

❖ Many nonpolar substances such as liquid

petrolatum (S= -13.4) fail to spread on water.
❖ Benzene spreads on water not because it is polar
but because the cohesive forces between its
molecules are much weaker than the adhesion for
water. ❖ The polar "heads" of the micelle, due to
❖ Spreading coefficient can be increased by the favourable interactions with water, form a
addition of surfactants hydrophilic outer layer that in effect protects the
❖ The surface activity of a particular surfactant hydrophobic core of the micelle.
depends on the balance between its hydrophilic
and hydrophobic properties
❖ The compounds that make up a micelle are
❖ The application of spreading coefficients in typically amphiphilic in nature, meaning that not
pharmacy should be fairly evident. only are micelles soluble in protic solvents such
 as water but also in aprotic solvents as a reverse The Solid-Gas Interface
micelle.
❖ reverse micelle: hydrophobic heads ang nasa ❖ Factors affecting adsoption of a gas:
labas • Chemical nature of the adsorbent (the
❖ Micelles are important in many uses of material used to adsorbed the gas) and the
surfactants for their capacity to solubilize water- adsorbate (the substance being adsorbed)
insoluble compounds. • the surface area of the adsorbent
❖ Vesicles are model systems for biological cells • Temperature
and can be used for entrapping active compounds • Partial pressure of adsorbed gas.
in their insides
Physical Adsorption
• Besides, vesicles and micelles are used as
(two types of adsorption)
microreactors for performing chemical
reactions and preparing solid nanoparticles ❖ Physical adsorption – associated with Van der
of varied shapes Waals (very weak bond) forces, is reversible, the
removal of adsorbate from the adsorbent being
Reversible monomer-micelle thermodynamic
known as desorption.
equilibrium.
❖ Chemisorption or chemical adsorption - which
the adsorbate is attached to the adsorbent by
primary chemical bonds, is irreversible.

❖ The relationship between the amount of gas

physically adsorbed on a solid and the
❖ The black circles represent the surfactant heads equilibrium pressure or concentration at constant
(hydrophilic moieties) and the black curved lines temperature yields an adsorption isotherm. (graph
represent the surfactant tails (hydrophobic that explains the extent of adsorption ( P)
moieties). ❖ The term isotherm refers to plot at constant
❖ (A) A micelle and (B) a vesicle of spherical temperature
shape. The alkyl chains were represented in a
Adsorption Isotherm
disordered state reminiscent of the liquid-like
structure of the aggregate core. ❖ The extent of the adsorption of a gas onto a solid
❖ Such a representation is closer to reality than that ❖ This is a graph that shows the amount of
where the alkyl chains are represented straight adsorbate/gram of adsorbent as a function of the
and normal to the assembly surface. equilibrium
❖ A surfactant may affect the activity of a drug or ❖ Three types of isotherm: Langmuir, Freundlich
may itself exert drug action. As an example of and BET Isotherm
the first case, the penetration of hexylresorcinol • Langmuir Isotherm – describes chemical
into the pinworm Ascaris is increased by the adsorption
presence of high concentration of surfactant. ▪ This shows the amount of gas adsorbed
❖ This potentiation of activity is due to a onto a solid increases with pressure but
reduction in interfacial tension between the reached a maximum (have saturation
liquid phase and the cell wall of the organism. point) and remains constant thereafter.
As a result, the adsorption and spreading of ▪ This indicates the formation of a gas
hexylresorcinol over the surface of the organism monolayer on the surface of the solid
is facilitated. ▪ This are often indicative of
chemisorption
ADSORPTION AT SOLID INTERFACES
• Freundlich Isotherm
❖ The principles of solid-liquid adsorption are ▪ This shows the amount of gas adsorbed
utilized in decolorizing solutions, adsorption per mass of the solid increases as the
chromatography, detergency and wetting. pressure increases.
▪ This indicates multilayer adsorption
Adsorption absorbate (physical adsorption), which indicates
Attractive physical adsorption.
▪ This does not reach saturation point
Cohesion Adhesion
“similar” vs “dissimilar” • BET Isotherm
▪ Brunauer, Emmett, and Teller
absorbent modifies the Lanmgmuir’s approach.
▪ This addresses the inability of the
Langmuir Isotherm to describe cases
 Wetting (7-9)
where molecules adsorb to other
molecules already adsorbed on the ❖ Contact angle: main property that
surface, thus creating multilayers. describes wetting
▪ This have sigmoidal shape ❖ Amphipiles (surfactants): affinity
for both polar & non polar

Lipo : HLB
The Solid-Liquid Interface Hydro : HLB
❖ Drugs/excipients such as dyes, alkaloids, fatty
acids, and even inorganic acids and bases may be
adsorbed from solutions into solids such as Wetting and Detergency
charcoal and alumina. (type of clay)
❖ A wetting agent, is a surfactant that, when
❖ Investigation include the adsorption of diphtheria
dissolved in water, lowers the advancing contact
toxin and several bacteria by various clays
angle and aids in displacing an air phase at the
❖ MW, MS -> struggle to refuse
surface and replacing it with a liquid phase.
❖ They concluded that attapulgite, a hydrous
magnesium aluminum silicate, was superior to
kaolin as an intestinal adsorbent. (slick to Surfactant
surface)
- Lower surface
Activated Charcoal tension & contact
angle
❖ The activated charcoal has been studied its drug
adsorptions and its effect on the bioabsorption in CA = WP
man, and have been concluded that reasonable in
vivo predictions could be made from in vitro • Examples of the application of wetting to
studies concerning the antidotal effectiveness of pharmacy and medicine include the
activated charcoal. displacement of air from the surface of
❖ Universal antidote sulfur, charcoal and other powders for the
• Activated charcoal purpose of dispersing these drugs in liquid
• Tannic acid vehicles
• Magnesium oxide • For example, straight chain alcohols,
❖ Activated charcoal is used as an antidote in amines, and acids are amphiphiles that
poisonings by sulfonylureas such as tolbutamide, change from being predominantly
acetohexamide and other drug and nondrug hydrophilic to lipophilic as the number of
compounds. carbon in the alkyl chain is increased.
❖ Activated charcoal has been used to adsorb • The most important action of a wetting
acetaminophen (toxic metabolite: NAPQI), while agent is to lower the contact angle between
acetylcysteine (antidote of paracetamol; the surface and the wetting liquid. The
neutralize NAPQI) is used to neutralize the toxic contact angle is the angle between a liquid
metabolites that deplete hepatic glutathione. droplet and the surface over which it spread.
❖ However, there has been concern that activated • CA = better WP
charcoal will adsorb the acetylcysteine as well as • The contact angle between a liquid and a
the acetaminophen and reduce or nullify the solid may by 0° , signifying complete
effectiveness of acetylcysteine in preventing wetting, or it may approach 180° , at which
liver damage and kidney failure. wetting is insignificant (no wetting at all)
0° = better wetting
• Detergents ( 13-16: hydrophilic) are
mataas attraction surfactants that are used for the removal of
sa water dirt. Detergency (lower surface tension) is a
complex process involving the removal of
foreign matter from surfaces.
• The process includes many of the actions
characteristic of specific surfactants
APPLICATION OF SURFACE ACTIVE
AGENTS
Examples of Surfactants
• In addition to the use or surfactants as
❖ Anionic
emulsifying agents, detergents, wetting
agents, and solubilizing agents, they find • Sodium and Potassium salts of straight chain
application as antibacterial and other fatty acids
protective agents and aids to the absorption • Sulfates and Sulfonates
of drugs in the body. • Monoalykyl phosphates
• Emulsifier : mixture of two immiscible • N-Acyl taurines, Acyl isethionates and N-
▪ Lowers surface tension Acylsarcocinates
▪ O/W - HLB (8-18) ❖ Cationic
▪ W/O - HLB (3-6) • Alkylbenzyldimethyl ammonium salts –
❖ Quaternary ammomium compounds (NH4+) antibacterial
are examples of cationic -surface-active agents • Alkyltrimethyl ammonium salts
that in them possess antibacterial activity ❖ Nonionic
❖ The agents are adsorbed on the cell surface and • Polyoxyethylene alkyl ethers
supposedly bring about destruction by increasing • Fatty acid alkanolamides
the permeability or “leakiness” of the lipid cell • Sorbitan fatty acid esters (SPAN)
membrane. • Polyoxyethylene sorbitan fatty acid esters
❖ Death then occurs through a loss of essential (TWEEN)
materials from the cell. • Alkyl polyglucosides
❖ Zwitterionic
❖ Both gram-negative and gram-positive • N-alkylbet
organisms are susceptible to the action of the
cationic quaternary compounds, Foams and Antifoaming Agents – HLB: 1-3 (hydro
❖ whereas anionic agents attack grampositive & lipo)
organisms more easily than are gram-negative
❖ Any solution containing surface-active materials
bacteria.
produce stable foams when mixed intimately
❖ Nonionic surfactants are least effective as
with air.
antibacterial agents.
❖ Foam is a relatively stable structure consisting of
absorption in stomach air pockets enclosed within thin films of liquid,
absorption in small intestine the gas-in-liquid dispersion being stabilized by a
❖ Polyoxyethylene lauryl ether reduced the
foaming agent
absorption of propicillin in the stomach and
❖ The foam dissipates as the liquid drains away
increased it in the small intestine
from the area surrounding the air globules, and
❖ It is well-known fact that some surfactants
the film finally collapses.
increase the rate of intestinal absorption, while
❖ Agents such as alcohol, ether, castor oil, and
others decrease it.
some surfactants may be used to break the foam
❖ Some of these effects may result from alteration
and are known as antifoaming agents
of the membrane by the surfactant.
Pharmaceutical applications and consequences of
Classification of Surfactants
adsorption
❖ Anionic – (-) charge. Used in cosmetics, but
❖ Adsorption of poisons/toxins
have unpleasant taste and are skin irritating.
❖ The universal antidote for use in reducing the
Incompatible with cationic surfactants only
effects of poisoning by the oral route is
❖ Cationic – (+) charge. Used as antibacterial
composed of activated charcoal, magnesium
agents, hair conditioners and fabric softeners.
oxide, and tannic acid
Incompatible with anionic surfactants only.
❖ Nonionic – no charge. Not affected by the More recent use of adsorbents has been in dialysis
presence of salt or pH changes (liver damage) to reduce toxic concentrations of
❖ Zwitterionic (positive & negative)– compatible drugs by passing blood through a hemodialysis
with ALL types of surfactants, depending on the membrane over charcoal and other adsorbents
pH of medium. Main use is as CO-surfactants to
boost foaming prop of others
Taste Masking

❖ Drugs such as diazepam may be adsorbed onto

solid substrates to minimize taste problems, but
care should be taken to ensure that desorption
does not become a rate limiting step in the
absorption process

Haemoperfusion

❖ Carbon hemoperfusion is an extracorporal

method of treating cases of severe drug
overdoses and originally perfusion of the blood
❖ A Wilhelmy plate is a thin plate that is used to
directly over charcoal granules.
measure equilibrium surface or interfacial
Adsorption in drug formulation tension at an air-liquid or liquid-liquid interface.
➢ In this method, the plate is oriented
❖ Beneficial uses include adsorption of surfactants perpendicular to the interface, and the force
and polymers in the stabilization of suspension, exerted on it is measured.
and adsorption of surfactants into poorly soluble
solids to increase their dissolution rate through Pendant drop
increased wetting.
❖ Problems may arise from the adsorption of ❖ The liquid is injected from a needle so that it
forms a drop on the tip of the needle. The drop is
medicaments by adsorbents such as antacids,
which may be taken simultaneously by the then optically observed and the surface tension is
calculated from the shape of the drop.
patient, or which may be present in the same
❖ For tensiometers, which use this method, a
formulation; and from the adsorption of
medicaments in the container walls, which may computer controlled instrument and a
sophisticated software is mandatory.
affect the potency and possibly the stability of
the product. Bubble Pressure
Solution – Container = sorption ❖ In this method a capillary tube is first immersed
Container – solution = letse (i-search niyo in the liquid sample. subsequently constant flow
spelling) of gas is purged through the tube forming small
Surface Tension Measurements bubbles into the liquid.
❖ The pressure needed to form a bubble is
1. Du Nouy – measures the maximum pull on measured and the surface tension of the sample
the ring by the surface is calculated from the pressure difference
2. Wilhelmy plate – measures equilibrium between inside and outside the bubble and the
surface or interfacial tension radius of the bubble.
3. Pendant Drop – based on the shape of the
drop. Volumetric tensiometers
4. Bubble Pressure – based on the pressure ❖ Measurement principle: Volumetric
5. Volumetric Tensiometers – based on the tensiometers measure surface tension by
size of the drops investigating the size of drops that can be made
from the sample
du Noüy ring method: The traditional method used
to measure surface or interfacial tension. Wetting ❖ The sample is pumped into a capillary at a
properties of the surface or interface have little constant rate. The drops that form at the end of
the capillary increases in size and eventually fall.
influence on this measuring technique. Maximum
pull exerted on the ring by the surface is measured. The time between drops is recorded and from
this the size of the drop is obtained. The higher
Du Noüy-Padday metho: A minimized version of the surface tension the larger drops.
Du d Noüy method uses a small diameter metal ❖ Volumetric tensiometers measure surface tension
needle instead of a ring, in combination with a high in order to control chemical additives in aqueous
sensitivity microbalance to record maximum pull. liquids