PHYSICAL PHARMACY

(MIDTERM COVERAGE)

Lima, Mary Loise L.

BS Pharmacy II A
I. Solubility and Distribution Phenomena Semipolar Solvents
Solubility → such as ketones and alcohols, can induce a certain
degree of polarity in nonpolar solvent molecules, so
→ Concentration of a substance (solute) that dissolves in that, for example, benzene, which is readily
a given volume of solution (solvent) at a certain polarizable, becomes soluble in alcohol
temperature to form a homogenous solution of the → semipolar compounds can act as intermediate to
solute in the solvent bring about miscibility of polar and nonpolar liquids
→ Spontaneous interaction of two or more substances to
form a homogenous molecular dispersion Polarity of Some Solvents and the Solutes that Readily Dissolve
in Each Class of Solvent
Saturated Solution

→ Is one in which the solute in solution is in equilibrium

with the solid phase

Unsaturated or Subsaturated Solution

→ Is one containing the dissolved solute in a

concentration below that necessary to complete
saturation at a definite temperature.

Supersaturated Solution

→ Is one that contains more of the dissolved solute than

it would normally contain at a definite temperature,
were the undissolved solute present SOLUBILITY OF LIQUIDS IN LIQUIDS

Solubility Definition in the United States Pharmacopeia → Liquid-liquid systems can be divided into two
categories according to solubility of the substances in
one another:

a) Complete miscibility→ polar and semipolar solvents

mix in all proportions; Ex: water and alcohol, glycerine
and alcohol, acetone and alcohol

b) Partial miscibility→ a pair of liquid is considered

partially miscible if there is a set of compositions over
which the liquids will form a two-phase liquid system.
SOLVENT – SOLUTE INTERACTIONS This is a common situation where one is polar and the
other non-polar (such as water and vegetable oils)
Polar Solvents
Miscibility
→ Dissolve ionic solutes and other polar substances
→ Is a liquid with molecules that have a slight electrical → mutual solubilities of the components in liquid-liquid
charge due to its shape systems
→ Ex: water, most alcohols, formic acid, hydrogen
fluoride, and ammonia SOLUBILITY OF SOLIDS IN LIQUIDS

Nonpolar Solvents → Systems of solids in liquids include the most frequently

encountered and probably the most important type of
→ Are unable to reduce the attraction between the ions pharmaceutical solutions.
of strong and weak electrolytes because of the → Solubility is the interaction between particles of the
solvents low dielectric constants. Nor can the solvents solute and the solvent. Hence, it depends on the
break covalent bonds and ionize weak electrolytes, nature of the solute and the solvent, as well as on the
because they belong to the group known an aprotic temperature and pressure. But the solubility of solids
solvents, and they cannot form hydrogen bridges with in liquids is independent of pressure.
nonelectrolytes → Solubility of solids in liquids:
→ Ex: carbon tetrachloride (CCI4), benzene (C6H6),
diethyl ether (CH3CH2OCH2CH3), hexane The solubility of solids in liquids depends upon two factors,
(CH3(CH2)4CG3), methylene chloride (CH2Cl2)
a) Nature of the solute and solvent
b) The temperature
II. Coarse Dispersions → Deflocculated particles – settle slowly and eventually
form sediment in which aggregation occurs with the
SUSPENSIONS
resultant formation of a hard cake that is difficult to
Pharmaceutical Suspension resuspend.

→ A coarse dispersion in which insoluble solid particles Surface Free Energy

are dispersed in a liquid medium.
∆𝐺 = 𝛾𝑆𝐿 × ∆𝐴
→ The particles have diameters for the most part greater
than 0.1 mcm, and some of the particles are observed Settling in Suspensions
under the microscope to exhibit Brownian movement
if the dispersion has a low viscosity. Theory of Sedimentation

Physical Stability of Suspensions → The velocity of sedimentation is expressed by

Stoke’s law:
→ the condition in which the particle do not aggregate
and in which they remain uniformly distributed 𝑑 2 (𝜌𝑠 − 𝜌𝑜 )𝑔
throughout the dispersion.
𝑣=
18𝑛𝑜
Desirable Qualities of an Acceptable Suspension → Where:
a) The suspended material should not settle rapidly. 𝑣 – the terminal velocity in cm/sec
b) The particles that do settle to the bottom of the d – the diameter of the particle in cm
container must not form a hard cake but should be 𝜌𝑠 𝑎𝑛𝑑 𝜌𝑜 – the densities of the dispersed
readily redispersed into a uniform mixture when the phase and dispersion
container is shaken. g – acceleration due to gravity
c) The suspension must not be too viscous to pour freely
𝑛𝑜 – is the viscosity of the dispersion
from the orifice of the bottle or to flow through a
medium in poise
syringe needle.

Desirable Qualities of an External Lotion → Stoke’s law can also be written this way:

a) The product must be fluid enough to spread easily 𝑣 ′ = 𝑣𝜀 𝑛

over the affected area and yet must not be so mobile
that it runs off the surface to which it is applied. → Where:
b) The lotion must dry quickly and provide an elastic 𝑣 ′ – is the rate of fall at the interface in
protective film that will not rub off easily cm/sec
c) It must have an acceptable color and odor 𝑣 – is the velocity of sedimentation according
to Stoke’s law
Interfacial Properties of Suspended Particles
𝜀 - represents the initial porosity of the
→ A system is thermodynamically unstable when the system
particles are highly energetic and tend to regroup in 𝑛 – measure of the hindering of the system
such a way as to decrease the total area and reduce
the surface free energy. Effect of Brownian Movement
→ When unstable, the particles tend to flocculate – to → For particles having a diameter of about 2 to 5 μm,
form light, fluffy conglomerate that are held together Brownian movement counteracts sedimentation to a
by weak van der Waals forces. measurable extent at room temperature by keeping
→ Under certain conditions, the particles may adhere by the dispersed material in random motion.
stronger forces to form what are termed aggregates. → Critical radius(r) – below which particles will be kept in
→ Caking often occurs by the growth and fusing together suspension by kinetic bombardment of the particles by
of crystals in the precipitates to produce a solid the molecules of the suspending medium.
aggregate. → Brownian movement of the smallest particles in a field
→ Equilibrium is reached when ∆G=0. of particles of a pharmaceutical suspension is usually
→ Flocculated particles – are weakly bonded, settle eliminated when the sample is dispersed in a 5-%
rapidly, do not form a cake, and are easily glycerin solution, having a viscosity of about 5
resuspended centipoise.
 Sedimentation of Flocculated Particle b) The application of the principles of flocculation to
produce flocs that, although they settle rapidly, are
→ In flocculated systems – flocs tend to fall together, easily resuspended with a minimum of agitation.
producing a distinct boundary between the sediment
and the supernatant liquid. The liquid above the
→ Structured vehicles – are pseudoplastic and plastic in
sediment is clear because even the small particles
nature.
present in the system are associated with the flocs.
→ Whatever approach is used, the product must:
→ In deflocculated suspension – no clear boundary is
✓ Flow readily from the container
formed and the supernatant remains turbid for a
✓ Possess a uniform distribution of particles in
considerably longer period of time.
each dose
→ Initial rate of settling of flocculated particles is
determined by the floc size and the porosity of the Wetting of Particles
aggregated mass. The rate depends on compaction and
→ Wettability of a powder can be ascertained easily by
rearrangement processes within the sediment.
observing the contact angle that powder makes with
→ Subsidence – term used to describe the settling in
the surface of the liquid.
flocculated systems.
→ The angle is approximately 90° when the particles are
Sedimentation Parameters floating well out of the liquid.
→ A powder that floats low in the liquid has a lesser
Two Parameters used in Sedimentation:
angle.
a) Sedimentation Volume, V, or height → One that sinks obviously shows no contact angle.
F=𝑉𝑢 ⁄𝑉𝑜 → Powders that are not easily wetted by water and
accordingly show a large contact angle are said to be
Wherein: hydrophobic.
→ Powders that are readily wetted by water when free
F – sedimentation volume
of adsorbed contaminants are called hydrophilic.
𝑉𝑢 – ultimate volume of the sediment
𝑉𝑜 – volume of the suspension Controlled Flocculation

→ Sedimentation volume can have values ranging from Materials used to Produce Flocculation
less than 1 to >1
1. Electrolytes – act as flocculating agents by reducing
→ F – is normally less than 1 the electric barrier between the particles, as
→ The ultimate volume of sediment is smaller than the evidenced by a decrease in the zeta potential and the
original volume of suspension formation of a bridge between adjacent particles so as
to link them together in a loosely arranged structure.
b) Degree of flocculation, β
2. Surfactant – both and ionic, have been used to bring
𝛽 = 𝑉𝑢 ⁄𝑉∞
about flocculation of suspended particles. The
→ The degree of flocculation is a more fundamental concentration necessary to achieve this effect would
paremeter than F because it related the volume of appear to be critical because the compounds can also
flocculated sediment to that in a deflocculated system. act as wetting and deflocculating agents to achieve
We can therefore say that: dispersion.

𝑢𝑙𝑡𝑖𝑚𝑎𝑡𝑒 𝑠𝑒𝑑𝑖𝑚𝑒𝑛𝑡 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑓𝑙𝑜𝑐𝑐𝑢𝑙𝑎𝑡𝑒𝑑 𝑠𝑢𝑠𝑝𝑒𝑛𝑠𝑖𝑜𝑛 3. Hydrophilic polymers – acts as protective colloids, and
→ 𝛽 = 𝑢𝑙𝑡𝑖𝑚𝑎𝑡𝑒 𝑠𝑒𝑑𝑖𝑚𝑒𝑛𝑡 𝑣𝑜𝑙𝑢𝑚𝑒 𝑜𝑓 𝑑𝑒𝑓𝑙𝑜𝑐𝑐𝑢𝑙𝑎𝑡𝑒𝑑 𝑠𝑢𝑠𝑝𝑒𝑛𝑠𝑖𝑜𝑛
particles coated in this manner are less prone to cake
that are uncoated particles. Theses polymers exhibit
pseudoplastic flow in solution, and this property
Formulation of Suspensions serves to promote physical stability within the
suspension.
Preparation of physically stable suspensions fall into two
categories:
Flocculation in Structured Vehicles
a) The use of structured vehicle to maintain
deflocculated particles in suspension → Suspending agent is frequently added to retard
sedimentation of the flocs. This can lead to
incompatibilities, depending on the initial particle
 charge and the charge carried by the flocculating → Supersaturation ratio:
agent and the suspending agent. 𝑐 2𝛾𝑀
𝐼𝑛 =
Rheologic Considerations
𝑐𝑜 𝑁𝑘𝑇𝜌𝑅
Wherein:
→ The ideal suspending agent should have a high 𝑐 - solubility of a small particle of radius (R)
viscosity at negligible shear, that is, during shelf 𝑐𝑜 - solubility of a very large crystalline particle
storage; and it should have a low viscosity at high 𝛾 - interfacial tension of the crystal
shearing rates, that is, it should be free-flowing during 𝜌 - density of the crystal
agitation, pouring, and spreading. Pseudoplastics 𝑀 - molecular weight of the solute
show these desirable qualities. 𝑁 - Avogrado’s number
→ A suspending agent that is thizotropic as well as
𝑘 - Boltzmann constant
pseudoplastic should prove to be useful because it
𝑁 × 𝑘 = 8.314 × 107 𝑒𝑟𝑔𝑠 −1 𝑚𝑜𝑙𝑒 −1
forms a gel on standing and becomes fluid when
disturbed.
→ The physical stability of the suspension may be
Preparation of Suspensions enhanced owing to the repulsion of like-charged
particles.
→ On small scale, a suspension is prepared by grinding or
levigating the insoluble material in the mortar to a
smooth paste with a vehicle containing the dispersion
EMULSIONS
stabilizer and gradually adding the remainder of the
liquid phase in which any soluble drugs may be Emulsion
dissolved. The slurry is transferred to a graduate, the
mortar is rinsed with successive portions of the → a thermodynamically unstable system consisting of at
vehicle, and the dispersion is finally brought to the least two immiscible liquid phases, one of which is
final volume. dispersed as globules (the dispersed phase) in the
→ On large scale, dispersion of solids in liquids is other liquid phase (the continuous phase), stabilized
accomplished by the use of ball, pebble, and colloid by the presence of an emulsifying agent. The particle
mills. diameter of the dispersed phase generally extends
→ Colloid mill - is based on the principle of a high velocity, from about 0.1to 10𝜇𝑚.
cone-shaped rotor that is centered with respect to a
Emulsion Types:
stator at a small adjustable clearance. The suspension
is fed to the rotor by gravity through a hopper, sheared a) Oil-in-water emulsion – when the oil phase is
between the rotor and the stator, and forced out dispersed as globules throughout an aqueous
below the stator, where it may be recycled or drawn continuous phase.
off. b) Water-in-oil emulsion – when the oil phase serves as
Physical Stability of Suspension the continuous phase.

→ Aggregate size was found to be inversely related to the Theories of Emulsification

freezing rate.
→ Particle growth is also destabilizing process resulting 1. Monomolecular Adsorption
from temperature fluctuations or Ostwald ripening → Amphiphiles - reduce interfacial tension because of
during storage. their adsorption at the oil-water interface to form
→ Fluctuations of temperature can change the particle monomolecular films.
size distribution and polymorphic form of a drug. → The dispersed droplets are surrounded by a coherent
→ When temperature is raised, crystals of drug may monolayer that helps prevent coalescence between
dissolve and form supersaturated solutions which two droplets as they approach one another.
favor crystal growth. → An additional effect promoting stability is the
→ The smaller the pore size, the higher is the presence of a surface charge, which will cause
supersaturation of the solution required for the repulsion between adjacent particles.
crystals to grow.
→ Rule of Bancroft – the type of emulsion is a function of
→ The stability of suspensions may also decrease owing
the relative solubility of the surfactant, the phase in
to interaction with excipients dissolved in the
which it is more soluble being the continuous phase.
dispersion medium.
 2. Multimolecular Adsorption and Film Formation → Filtration is conducted under negative pressure
→ Hydrated lyophilic → colloids differ from the synthetic through a dialysis membrane supported in a Buchner
surface active agents in that: funnel.
 They do not cause an appreciable lowering of
Electrodialysis
interfacial tension and
 They form a multi-rather than a → the use of electric potential across membrane in
monomolecular film at the interface. dialysis and ultrafiltration
➢ their action as emulsifying agents is
Dialysis
due mainly to the latter effect
because the films thus formed are → occurs in vivo
strong and resist coalescence.
Note: the more extended the particle, the greater is its specific
3. Solid – Particle Absorption
surface area, thus greater opportunity for attractive forces to
Types of Emulsifying Agent: develop between the particles of the dispersed phase and
dispersing medium.
a) Surface-active agents, which are adsorbed at oil-water
Types of Colloidal Systems
interfaces to form monomolecular films and reduce
interfacial tension. 1. Lyophilic Colloids
b) Hydrophilic colloids, which form a multimolecular film → Solvent – loving colloids
around the dispersed droplets of oil in an o/w → Has great affinity to their dispersion medium
emulsion. Solvation
c) Finely divided solid particles, which are adsorbed at
the interface between two immiscible liquid phases → the attachment of solvent molecules to the molecules
and form what amounts to a film of particles around of the dispersed phase
the dispersed globules. Hydration

→ hydrophilic colloids wherein water is the dispersion

medium
III. Colloidal Dispersions
Lipophilic Colloids
Dispersion
→ lyophilic colloids in non-aqueous, organic solvents
→ consists of at least one internal phase that is dispersed
in a dispersion medium 2. Lyophobic Colloids
→ solvent-hating colloids due to absence of a solvent
3 Types of Dispersed Systems sheath around the particle
1. Molecular dispersions - <1nm particle size Methods in Preparing Lyophobic Colloids
2. Colloidal Dispersions - 1nm-O.5mcm
3. Coarse Dispersions - >0.5mcm a) Dispersion Method – coarse particles are reduced in
size.
Size and Shape of Colloidal Particles b) Condensation Method – materials of sub-colloidal
dimensions are caused to aggregate into particles
Specific Surface
within the colloidal size range.
→ surface area per unit weight or volume of material
Types of Colloidal Dispersions
Dialysis Dispersion Dispersed Colloid Type
medium phase
→ method of separation of colloidal particles by the use Solid Solid Solid sol
of a semi permeable membrane of collodion or Solid Liquid Solid emulsion
cellophane Solid Gas Solid foam
→ the pore size of which, will prevent the passage of Liquid Solid Sol, gel
colloidal particles yet permit small molecules and ions. Liquid Liquid Emulsion
Ultrafiltration Liquid Gas Foam
Gas Solid Solid aerosol
→ used to separate and purify colloidal material Gas Liquid Liquid aerosol
3. Association Colloids: Micelles and Critical Micelle → Movement from region of high conc to lower conc
Concentration until it reaches equilibrium
→ aka Amphiphilic Colloids
Osmotic Pressure
Amphiphiles/ surface-active agents
→ described by van’t Hoff equation
→ have two distinct regions of opposing solution
affinities within the same molecule or ion π = cRT

Micelles → where π= osmotic pressure; c= molar conc of solute;

R= ideal gas constant; T= temperature
→ aggregates that may contain 50 or more monomers
Sedimentation
Critical Micelle Concentration
→ rate of sedimentation is expressed in Stoke’s law
→ the concentration of monomer at which micelles form v= 2r2(p – po) g / 9 no
Aggregation Number → where v=velocity ; r = radius ; p= density ; g=
acceleration due to gravity ; no = viscosity
→ the number of monomers that aggregate to form a
micelle 2 Sedimentation Methods Used

Optical Properties of Colloids a) Sedimentation velocity technique

b) Sedimentation equilibrium
Faraday-Tyndall Effect
Viscosity
→ scattering of light by colloidal particles when a strong
beam of light is passed through a colloidal sol → resistance to flow of a system under an applied stress
n = no (1 + 2.5ϕ)
Ultramicroscope

→ can examine light points responsible for Tyndall cone → where n = viscosity of dispersion when the volume
fraction of colloidal volume of particles is ϕ; no =
Electron Microscope viscosity of dispersion medium

→ widely used to observe size, shape, and structure of Electrical Properties of Colloids
colloidal particles
1. Zeta (electrokinetic) potential
Light Scattering 2. Nernst (electrothermodynamic) potential

→ widely used for determining MW of colloids Electrokinetic Phenomena

Hc / t = 1/M + 2Bc
1. Electrophoresis
→ Where
→ involves movement of a charged particle through a
H = constant for particular system
liquid under the influence of an applied potential
c = conc. of solute (g/cm3)
t = turbidity (cm-1) difference.
2. Electroosmosis
M = MW (g/mole)
B = interaction constant → opposite in principle of electrophoresis. This causes a
charged particle to move relatively to the fluid, which
Kinetic Properties of Colloids is stationary.
3. Sedimentation Potential
Brownian Motion
→ reverse of electrophoresis, the creation of a potential
→ random movement of colloidal particles when particles undergo sedimentation.
4. Streaming Potential
with in particle size → differs from electroosmosis in that forcing a liquid to
and stops with viscosity of medium flow through a plug or bed or particles.

Diffusion Donnan Membrane Equilibrium

→ direct result of Brownian movement → Gives the ratio of concentrations of the diffusible
anion outside and inside the membrane at equilibrium
Stability of Colloid Systems Factors Affecting Solubilization

Achieved by two means: 1. Lipophilic alkyl chain length of surfactant – enhances

solubilization
1. Providing the dispersed particles with an electric
2. Radius of hydrocarbon core –enhances solubilization
charge.
3. Polarity of surfactant = solubilizing nature of
2. Surrounding each particle with a protective solvent
surfactant for semi-polar drugs
sheath.
4. pH – alter equilibrium between ionized and un-ionized
Lyophobic sol drug

→ thermodynamically unstable Pharmaceutical Applications of Colloids

→ stabilized by presence of electric charges on their 1. Hydrogels
surface → colloidal gel wherein water is the dispersion medium;
Schulze-Hardy rule use for wound healing, as scaffolds in tissue
engineering, and in sustained-release delivery
→ the precipitating power increases rapidly with the systems.
valence or charge of ions → Microparticles – small (o-2.5 mcm), loaded
microspeheres of natural or synthetic polymers;
Lyophilic and Association colloids
carriers for vaccine and anticancer drugs.
→ thermodynamically stable
2. Emulsions and Microemulsions
Salting out → potential drug delivery systems because of improved
→ agglomeration and sedimentation of particles upon drug solubilization
addition of sufficient salt to colloids
3. Liposomes
Hofmeister or lyotropic series → consist of an outer uni- or multilaminar membrane
and an inner liquid core; applied as drug delivery
→ ranks cations and anions in order of coagulation of
systems
hydrophilic sols

Coacervate 4. Micelles
→ structures similar to liposomes but don’t have inner
→ colloid-rich layer of colloid aggregate liquid compartment; can be used for water-soluble
Coacervation biocompatible microcontainers

→ phenomenon where macromolecular solutions 5. Nanoparticles

separate into 2 liquid layers → submicroscopic colloidal drug carrier system
composed of an oily or an aqueous core surrounded
Sensitization and Protective Colloidal Action
by a thin polymer membrane
Protection a) Interfacial nanodeposition of monomer
b) Interfacial nanodeposition of a
→ phenomenon wherein hydrophile is adsorbed on preformed polymer
hydrophobic particle and stabilizes the system 6. Nanocrystals
→ Used in biology and medicine
Protective Colloid

→ the added hydrophilic sol

Gold Number

→ expresses protective property of colloids

Solubilization

→ the ability of micelles to increase solubility of materials

that are normally insoluble or slightly soluble in
dispersion medium used.
IV. Buffered and Isotonic Solutions the ratio of [base] to [acid] is about 1 to 10. That is, there
must be at least 1 part of the basic color to 10 parts of the
Buffers
acid color before the eye can discern a change in color from
→ compounds or mixtures of compounds that, by their acid to alkaline.
presence in solution, resist change in pH upon the Universal Indicator
addition of small quantities of acid or alkali.
→ combination of weak acid and its conjugate base (i.e. → consisting of a mixture of methyl yellow, methyl red,
salt), or a weak base and its conjugate acid. bromothymol blue, thymol blue and phenolphthalein
→ covers the range from pH 1 to 11
* If 1ml of a 0.1-N HCl solution is added to 100mL of pure water,
the pH is reduced from 7 to 3. If the strong acid is added to a Determination of pH:
0.01-M solution containing equal quantities of acetic acid and
1. Colorimetric Method
sodium acetate, the pH is changed only 0.09 pH units.
→ determination of pH is probably less accurate and less
Buffer Action convenient but also less expensive
→ may be used in the determination of the pH of
→ resistance to a change in pH
aqueous solutions that are not colored or turbid
Buffer Equation → particularly useful for the study of acid-base reactions
in nonaqueous solutions
→ Henderson-Hasselbalch Equation Steps:
→ used to calculate the pH of buffer solution and the a) Determine the approximate pH of the solution by
change in pH upon the addition of an acid or base. the addition of several drops of a universal
pH = pKa + log [salt]/[acid] indicator (wide-range pH papers, prepared by
→ where: pKa – negative logarithm of Ka applying a universal indicator to paper strips, may
→ important in the preparation of buffered be used)
pharmaceutical solutions. b) A series of Clark-Lubs buffer solutions as modified
→ it is satisfactory for calculations within the pH range of by Bower and Bates, differing by 0.2 pH unit and
4 to 10. within the pH range of the unknown solution, are
chosen. Several drops of an indicator solution,
Some Factors Influencing the pH of Buffer Solutions:
having a pKIn approximately equal to the pH of
1. Addition of neutral salts – by altering the ionic strength the unknown solution so that it changes color
2. Dilution within the pH range under consideration, are
Dilution Value – change in pH on diluting the added to each buffer sample and to the unknown
buffer solution to one half its original solution contained in suitable test tubes
strength. c) The colors of the buffers of known pH are
- positive dilution value ( pH rises with matched with the color of the unknown solution
dilution); negative dilution values (pH (the pH of the unknown solution can be
decreases with dilution of the buffer) determined to within 0.1 pH unit)
3. Temperature
Temperature coefficient – change in pH with 2. Electrometric Method
temperature → More accurate determination of pH

Buffer Capacity
 Drug in solution may often act as its own buffer over a
definite pH range. However, additional buffers are → known as buffer efficiency, buffer index, and buffer
frequently added because the buffer capacity is often too value.
weak to counteract pH changes brought about by the → magnitude of the resistance of a buffer to pH changes.
carbon dioxide of the air and the alkalinity of the bottle. → ratio of the increment of strong base (or acid) to the
small change in pH brought about by this addition.
 pH indicators may be considered as weak acids or weak
bases that act like buffers and also exhibit color changes as Buffers in Pharmaceutical and Biologic Systems:
their degree of dissociation varies with pH. 1. In Vivo Biologic Buffer Systems
a. Blood
 It is known from experience that one can’t discern a change → maintained at a pH of about 7.4 by the
from the acid color to the salt or conjugate base color until so-called primary buffers in the plasma
 and the secondary buffers in the c. Consider the individual concentrations of the buffer
erythrocytes. salt and acid needed to obtain a suitable buffer
Plasma capacity. A concentration of 0.05 to 0.5 M is usually
→ contains carbonic acid/bicarbonate and sufficient; and a buffer capacity of 0.01 to 0.1 is
acid/alkali sodium salts of phosphoric generally adequate
acid as buffers. d. Other factors of some importance in the choice of a
Erythrocytes pharmaceutical buffer include availability of
→ consists of 2 buffer systems: hemoglobin chemicals, sterility of the final solution, stability of the
/ oxyhemoglobin and acid / alkali drug and buffer on aging, cost of materials, and
potassium salts of phosphoric acid. freedom from toxicity. For example, a borate buffer,
because of its toxic effects, certainly cannot be used
*When pH of the blood goes below 6.9 or above 7.8, life is in to stabilize a solution to be administered orally or
serious danger parenterally.
*The pH of the blood in diabetic coma is alleged to drop as low e. One should determine the pH and buffer capacity of
as about 6.8. the completed buffered solution using a reliable pH
meter
b. Lacrimal Fluid
→ Tears Reduction in Tissue Irritation (due to large pH differences
between the solution being administered and the physiologic
→ have been found to have a great degree
environment in which it is used):
of buffer capacity, allowing a dilution of
1:15 with neutral distilled water before a. the lower the buffer capacity of the solution
an alteration of pH is noticed b. the smaller the volume used, for a given concentration
→ pH is about 7.4, with a range of 7 – 8 or c. the larger the volume and buffer capacity of the
slightly higher physiologic fluid
c. Urine
→ 24-hr collection of a normal adult has a ▪ Eye
pH averaging about 6.0. units → pH of solutions without marked pain or damage
→ it may be as low as 4.5 or as high as 7.8 may vary from 4.5 to 11.5
→ depends on buffer employed
2. Pharmaceutical Buffers ▪ Parenteral Solutions for injection into the blood
→ Buffer solutions are used frequently in pharmaceutical → usually not buffered, or they are buffered to a low
practice, particularly in the formulation of ophthalmic capacity so that the buffers of the blood may
solutions. They also find application in the colorimetric readily bring them within the physiologic pH
determination of pH and for those research studies in range
which pH must be held constant ▪ Oral Administration
→ The Clark-Lubs mixtures and their correcponding pH → absorbed rapidly in systems buffered at low
ranges: buffer capacity than in systems containing no
a. HCl and KCl -> 1.2 to 2.2 buffer or in highly buffered preparations (e.g.
b. HCl and K hydrogen phthalate -> pH 2.2 aspirin)
to 4.0 ▪ Nasal Delivery of Drugs
c. NaOH and K hydrogen phthalate -> pH → demands similar requirements in ophthalmic
4.2 to 5.8 preparations.
d. NaOH and KH2PO4 -> pH 5.8 to 8.0
e. H3BO3, NaOH and KCl -> pH 8.0 to 10.0

Preparation of Pharmaceutical Buffer Solutions

a. Select a weak acid having a pKa approximately equal

to the pH at which the buffer is to be used. This will
ensure maximum buffer capacity.
b. From the buffer equation, calculate the ratio of salt
and weak acid required to obtain the desired pH. The
buffer equation is satisfactory for approximate
calculations within the pH range of 4 to 10.