AUF CAMP – PHARMACY DEPARTMENT

PHYSICAL PHARMACY (LABORATORY)

Exercise 1: States of Matter
Lecturer: Mairre Louie D. Punsalan

OUTLINE  Beta prime (B’) - 28℃

Procedure  Stable beta form (B) – 34.5℃, most suitable as
Post Laboratory Discussion suppository base at body temperature
 States of Matter
 Phase Changes Amorphous
 Also known as glasses or supercooled liquids
 Non-crystalline; no definite order
OBJECTIVES
 To identify the state of matter and processes that water can  Have no definite and sharp melting points
go through
LIQUIDS
PROCEDURES  Possess less kinetic energy than do gases, but more than solids
 Occupy a definite volume because of their tendency to flow
Evaporation
 Take the shape of the containers that hold them
1. Dip your index finger in a beaker of water, then hold it upright.
 Denser than gases
2. Observe and record the time the water totally disappears.
 Not compressible
Liquefaction
1. Set the hot plate to 100 degrees Celsius. General Properties of Liquids
2. In a 500mL beaker, put 200g of ice. Boil using hot plate. Record  Surface tension – property of a liquid to resist an external force
the time.  Tendency in which the fluid surfaces try to shrink
3. In a separate 500mL beaker, place 200mL water and boil. into the minimum surface area possible
Record the time.  Examples: putting a drop of water in water, slowly
putting a paper clip (denser) in water, water striders
Condensation (insects)
1. Immerse a clean cloth in water and squeeze it to remove excess
water.  Viscosity
2. Put the wet cloth inside the Ziploc and trap some air inside and  Resistance of liquid to flow
seal it.  “Thickness” or “thinness” (lapot or labnaw)
3. Leave the Ziploc under direct sunlight for one hour. Observe.  Higher intermolecular force, higher viscosity
 Example: suspensions
POST-LABORATORY DISCUSSIONS
STATES OF MATTER  Vapor pressure
 Pressure exerted by its vapor when in equilibrium
 Solid with liquid or solid
 Liquid  Higher intermolecular force, lower vapor pressure –
 Gas since it will let the particles have the difficulty to
escape as gases
 Plasma (Mesophase)
GASES
SOLIDS
 Have kinetic energy (high) that produces rapid motion
 Characterized as having fixed shapes  tightly packed
 Held together by weak intermolecular forces
 Nearly incompressible
 Capable of filling all available space
 Have strong intermolecular forces  holds molecules together
 Are compressible
 Very little kinetic energy
 For many, are invisible
 Their atoms vibrate in fixed positions about an equilibrium
position, and so there is very little translational motion
PLASMA
Crystalline
 Also known as mesophase, liquid crystals, or supercritical fluid
 Molecules are arranged in repetitious three-dimensional lattice
units  Partly solid, partly liquid
 Have definite geometric forms  Tends to flow like liquid under extreme conditions
 Cubic – NaCl  Properties
 Tetragonal – urea  Rigid
 Hexagonal – iodoform  Organic in nature
 Rhombic – iodine  Polarizable groups (easily polarizable groups)
 Monoclinic – sucrose  Elongated
 Triclinic – boric acid
 Types
Polymorphism  Smectic
 Condition where substances exist in more than one crystalline  Soap or grease-like
form  Rotate in 1-axis
 Have different stabilities, different physical properties such as  Mobile in two (2) directions
melting points and solubilities  Most important pharmaceutically
 Nematic
 Example: Theobroma oil (cacao butter) – can be in four (4)
 Thread-like
forms with different melting points; used as suppository base
 Rotate in 1-axis
 Unstable gamma form (Y) - 18℃
 Mobile in three (3) directions
 Alpha form (a) - 22℃

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 1: States of Matter
Lecturer: Mairre Louie D. Punsalan

 Cholesteric
 Special type of nematic
 Encountered in atherosclerosis, involved
in the incorporation of cholesterol and
lipids in the human macrophage, so it
will lead to an insoluble liquid
crystalline membrane, and ultimately
results in a plaque around the arteries
 Cholesterol can be regarded to
cholesteric

Higher temperature, greater number of molecules that will evaporate

 Practical uses
 Manufacture of bulk drugs and other biologicals
 Water manufacturing (demineralization)
Physical States (increasing energy)
 Factors affecting evaporation
 Temperature – directly proportional
 Pressure
 Concentration
 Surface area – directly proportional
 Agitation
 Type of product required
Solid. The molecules that make up a solid are arranged in regular, repeating CONDENSATION
patterns. They are held firmly in place but can vibrate within a limited area.
 Reverse process of evaporation: change from vapor to liquid
Liquid. The molecules that make up a liquid flow easily around one
 Prerequisites
another. They are kept from flying apart by attractive forces between them.
 Gas is cooled sufficiently or the pressure in the gas
Liquids assume the shape of their containers.
is increased sufficiently  prevents forces of
attraction between molecules to move apart
Gas. The molecules that make up a gas fly in all directions at great speeds.
 Greater pressure or lower temperature  weaker
They are so far apart that the attractive forces between them are
attractive force
insignificant.

Plasma. At the very high temperatures of stars, atoms lose their electrons.
The mixture of electrons and nuclei that results is the plasma state of
matter.

PHASE CHANGES

 Practical uses
 Crucial component of distillation
 Potable water manufacturing

 Factors affecting condensation

Deposition – formation of dry ice
 Temperature
S to L  melting L to S  freezing
 Vapor pressure
S to G  sublimation G to S  deposition
L to G  vaporization G to L  condensation
LIQUEFACTION
G to P  ionization P to G  deionization

EVAPORATION  Conversion of solids and gas to liquid (melting and

condensation)
 Conversion of a liquid to its vapor  Melting point – temperature and pressure at which a solid
becomes liquid
 Prerequisites
 Enough kinetic energy  overcome the  Liquefaction of gases – condensing gas to liquid
intermolecular forces (threshold – maximum  Practical uses
amount of kinetic energy that can be overcome)  Coals (liquid fuels)
 Heating (e.g., perspiration into the atmosphere)   Dissolution
result in a greater friction of the molecules between  Food preparation
the liquids  molecules escape the liquid surface  Production of liquid oxygen/nitrogen

Renhart M. Salas, fRPh 2|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 1: States of Matter
Lecturer: Mairre Louie D. Punsalan

SUBLIMATION

 Conversion of solid into gas (direct transition, does not pass

through the liquid state)
 Considered an endothermic process
 Analogous to boiling
 Vapor pressure = atmospheric pressure
 “Green chemistry” technique – does not require solvent or no
solvent is being used and no waste is being generated
 Not particularly efficient in separating volatile solids from one
another
 Examples: camphor, benzophenone, naphthalene, anthracene,
pyrene, and heating iodine crystals (then doing deposition by
putting ice, forms back as crystals; purple in color)

 Practical uses
 Purification of organic compounds with low melting
point
 Printing / textile industry

Renhart M. Salas, fRPh 3|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 2: Determination of Specific Gravity
Lecturer: Mairre Louie D. Punsalan

OUTLINE 5. The temperatures of the hydrometer and liquid tested should be

Post Laboratory Discussion equal
 Specific Gravity 6. Read the specific gravity of the sample liquid directly from the
calibration of the instrument
 Methods of Determining Specific Gravity
 Procedures
 Computations

OBJECTIVES
 To determine the specific gravity of different liquid
substances using specific gravity bottle (pycnometer),
Westphal balance and hydrometer

SPECIFIC GRAVITY
WESTPHAL BALANCE
 Ratio, expressed decimally, of the weight of a substance to the
 Founded by German chemist Karl Friedrich (KF) Mohr
weight of an equal volume of a substance chosen as a standard
(usually water; hydrogen for gases)  Also known as Mohr balance, Mohr-Westphal Balance
 Unequal-arm balance designed for determining density of
Weight of the substance solids and liquids by hydrostatic weighing
SG =
Weight of equal volume of water  Involves the use of a plummet (known mass and volume) and
riders (equalizer)
 Substances that have a specific gravity less than 1 are lighter  Convenient (three-decimal precision) but not accurate like
than water pycnometer
 Substances that have a specific gravity greater than 1 are
heavier than water

Types of Specific Gravity

 Absolute Specific Gravity
 The ratio of the weight of a given volume of a
substance in a vacuum at a given temperature to the
weight of an equal volume of water in a vacuum at
a given temperature
 Apparent Specific Gravity
 The ratio of the weight of a volume of the substance
to the weight of an equal volume of the reference
substance
 The reference substance is nearly always water at its
densest (4°C) for liquids; for gases it is air at room
temperature (21°C)
 Nonetheless, the temperature and pressure must be
specified for both the sample and the reference
METHODS OF DETERMINING SPECIFIC GRAVITY
Direct Method – gives the actual specific gravity
 By using hydrometer
 By using Mohr-Westphal balance
Indirect Method – need to compute first
 By using pycnometer
HYDROMETER
 Measures relative density or specific gravity of liquids based on
the concept of buoyancy, the force that causes objects to float
 Calibrated, graduated  accurate
 The lower density, the deeper a hydrometer sinks
1. Be sure the hydrometer is clean and dry
2. Place enough sample test solutions in a 100mL graduated
cylinder
3. Immerse the hydrometers slowly in liquid to a point below
which it naturally sinks
4. Do not make reading until the hydrometer and liquid are at rest
and free from air bubbles
1. The Westphal balance has an arm equipped with a plummet of
known volume and mass
2. Calibrate the balance using the different balances
3. Immersed the arm in the test solution and rebalanced using a
series of riders placed in the notched beam so that the indicator
points of the balance were coincident to each other
4. This gives the buoyant force of the liquid relative to water, and
hence the specific gravity, which may be obtained to four
decimal places
PYCNOMETER
 Specific Gravity Bottle
 Special glass bottle used to determine specific gravity
 Generally available for laboratory use in volumes from 1-
50mL; have fitted glass stoppers with capillary opening to allow
the trapped air and excess fluid to escape
 Use of thermometers – temperature, an underlying factor in SG
1. Wash and clean the pycnometer
together with the cap and thermometer.
Dry the pycnometer and cap in the oven.
In drying, do not include the
thermometer.
2. Allow to cool in a desiccator (no
moisture), and then weigh your empty
pycnometer using top loading balance
together with the cap and thermometer.
3. Fill the bottle with the sample liquid and
fit the thermometer and cap back to the
pycnometer with due precautions to
prevent bubbles to appear in the sample.
4. Allow the pycnometer with its contents
to reach 25℃, by immersing it in cool
water, and then wipe it dry and weigh.

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 2: Determination of Specific Gravity
Lecturer: Mairre Louie D. Punsalan

5. Remove the contents of the bottle and wash with water. Dry in Example
the oven and cool in the desiccator. A piece of glass weighs 38.525g in air and 23.525g when immersed in
6. Fill the bottle with distilled water and follow the same water. What is its specific gravity?
procedure observe when sample liquid was used.
Weight of solid in air
SG =
Weight of an equal volume of water
COMPUTATIONS
wt. of equal vol. of water = wt. of solid in air – wt. of solid in water
 Specific Gravity
 Pycnometer / Specific Gravity Bottle wt. of equal vol. of water = 38.525g – 23.525g = 15g (displaced water)
 Displacement / Plummet Method
SG = 38.525g / 15g = 2.5683
 Specific Gravity of Solids
 Solids heavier than and insoluble in water
SOLIDS HEAVIER THAN AND SOLUBLE IN WATER
 Solids heavier than and soluble in water
 Solids lighter than and insoluble in water
 Since the weights of equal volumes of any two substances are
 Granulated solids heavier than and insoluble in
proportional to their specific gravities. The previous procedure
water
may be used but since the substance is soluble in water, we
 Specific Volume
cannot immerse the solid in water but a substitute liquid is to be
used in which the solid is insoluble and whose specific gravity
SPECIFIC GRAVITY
is known.
SPECIFIC GRAVITY BOTTLE / PYCNOMETER
Example
Example
A crystal of a chemical salt weighs 6.423g in air and 2.873g when
A 50mL pycnometer is found to weigh 120g when empty, 171g when filled
immersed in an oil having a specific gravity of 0.858. What is the specific
with water, and 160g when filled with an unknown liquid. Calculate the
gravity of the salt?
specific gravity of the unknown liquid.

Weight of substance wt. of oil = wt. of subs. in air – wt. of subs. in oil
SG = wt. of oil = 6.423g – 2.873g = 3.55g (displaced oil)
Weight of equal volume of water

wt.of oil SG of oil 3.55g 0.858

wt. of subs. = wt. of subs. in pyc – wt. of pyc =  =
wt.of solid SG of solid 6.423g SG of solid
wt. of subs. = 160g – 120g = 40g
(3.55g)(SG of solid) = (6.423g)(0.858)
wt. of equal vol. of water = wt. of water in pyc – wt. of pyc (6.423g)(0.858)
wt. of equal vol. of water = 171g – 120g = 51g SG of solid = = 1.5524
3.55g

SG = 40g / 51g = 0.7843 SOLIDS LIGHTER THAN AND INSOLUBLE IN WATER

DISPLACEMENT OR PLUMMET METHOD
 Based on Archimedes’ principle
 “A body immersed in a liquid displaces an amount
of the liquid equal to its own volume and suffers an
apparent loss in weight equal to the weight of the
displaced liquid”
 Weigh plummet when suspended in water and
liquid; subtract these weights from the weight of
plummet in air
 Since the solid is lighter than water there is a need to immerse
it in water so that the volume of water displaced can be known.
This is done with the use of a sinker. The sinker is attached to
the solid to prevent it from floating.
 Weight of an equal volume of water = (Weight of substance in
air + weight of sinker in water) – Weight of sinker and
substance in water
Weight of substance in air
 SG =
Weight of an equal volume of water

Example
A glass plummet weighs 12.64g in air, 8.57g when immersed in water, and
9.12g when immersed in an oil. Calculate the specific gravity of the oil.
wt. of oil = wt. of plummet in air – wt. of plummet in oil
wt. of oil = 12.64g – 9.12g = 3.52g (displaced oil)
wt. of water = wt. of plummet in air – wt. of plummet in water
wt. of water = 12.64g – 8.57g = 4.07g (displaced water)
Example
A piece of wax weighs 16.35g in air, and a sinker weighs 32.84 g immersed
in water. When they are fastened together and immersed in water, their
combined weight is 29.68g. Calculate the specific gravity of the wax.
wt. of equal vol. of water = (wt. of subs. in air + wt. of sinker in water) –
wt. of sinker and subs. in water
wt. of equal vol. of water = (16.35g + 32.84g) – 29.68g
wt. of equal vol. of water = 19.51g

Weight of substance Weight of substance in air

SG = SG =
Weight of equal volume of water Weight of an equal volume of water
SG = 3.52g / 4.07g = 0.8649 SG = 16.35g / 19.51g = 0.8380

SPECIFIC GRAVITY OF SOLIDS GRANULATED SOLIDS HEAVIER THAN AND INSOLUBLE

SOLIDS HEAVIER THAN AND INSOLUBLE IN WATER IN WATER

 Simply divide the weight of the solid in air by the weight of  Weight of equal volume of water = (Weight of substance in air
water that it displaces when immersed in it. The weight of water + weight of bottle filled with water) – Weight of bottle filled
displaced (apparent loss of weight in water) is equal to the with substance and water
Weight of substance in air
weight of an equal volume of water.  SG =
Weight of an equal volume of water

Renhart M. Salas, fRPh 2|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 2: Determination of Specific Gravity
Lecturer: Mairre Louie D. Punsalan

Example
A bottle weighs 50.0g when empty and 96.8g when filled with water. If
28.8g of granulated metal are placed in the bottle and the bottle is filled
with water, the total weight is 118.4g. what is the specific gravity of the
metal?

wt. of equal vol. of water = (wt. of subs. in air + wt. of bottle w/ water) –
wt. of bottle w/ subs. and water
wt. of equal vol. of water = (28.8g + 96.8g) – 118.4g
wt. of equal vol. of water = 7.2g

Weight of substance in air

SG =
Weight of an equal volume of water
SG = 28.8g / 7.2g = 4

SPECIFIC VOLUME

 An abstract number representing the ratio, expressed decimally,

of the volume of a substance to the volume of an equal weight
of another substance taken as a standard (water), both having
the same temperature
 SG – weights of equal volumes
 SV – volumes of equal weights
 Thus, SG and SV are reciprocals; when multiplied
together, the product is 1.
 Specific volume tells us how much greater (or smaller) in
volume a mass is than the same weight of water
 Because specific gravity and specific volume are reciprocals, a
substance that is heavier than water will have a higher specific
gravity and a lower specific volume, whereas a substance that
is lighter than water will have a lower specific gravity and a
higher specific volume.
 It follows, therefore, that we may determine the specific volume
of a substance by dividing 1 by its specific gravity, and we may
determine the specific gravity of a substance by dividing 1 by
its specific volume

Examples
Calculate the specific volume of a syrup, 91.0mL of which weighs 107.16g.

volume of substance
SV =
volume of equal weight of water
 vol. of equal wt. of water can be derived from 107.16g, the
weight of the syrup. Since equal weight is required, then water
should also be 107.16g. Because water has a density of 1g/mL,
then its volume is 107.16mL.
SV = 91mL / 107.16mL = 0.8492

What is the specific volume of phosphoric acid having a specific gravity of

1.71?
1
SV = (from SV x SG = 1)
SG
SV = 1 / 1.71 = 0.5848

Renhart M. Salas, fRPh 3|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 3: Measuring Alcohol Content
Lecturer: Mairre Louie D. Punsalan

OUTLINE Uses of Simple Distillation

Post Laboratory Discussion  Concentration of alcohol
 Distillation  Concentrate fermented solutions
 Simple Distillation  Produce hard liquors
o Uses  Examples: fermented grape juice, distillation of
o Distilled and Undistilled Drinkss wine
 Vacuum Distillation
 USP Alcoholometric Table Fermented grapes can produce a maximum alcohol content of about 16%
and this is somehow the upper limit for most beers and wines. Yeast is the
organism used for fermentation. Yeast cannot survive in higher
OBJECTIVES
concentrations of solution, so that the fermentation process is maintained
 To be able to appreciate and identify the alcohol content by
(rationale of the 16% upper limit).
simple or vacuum distillation
 To know the practice uses and importance of distillation There are alcoholic drinks that contain a higher alcohol content such as
spirits (e.g., vodka, gin, rum; around 40% by volume). The percentage level
DISTILLATION can be concentrated by the use of distillation. Distillation can concentrate
fermented solutions and produce hard liquors.
 Purification method for liquids
 Separate components of a mixture if they have significantly
different boiling points
 Depends on the degree of the boiling points of certain liquids in
a mixture
 Liquid is boiled in the distilling flask, then vapors travel to
another section of the apparatus where they come in contact
with a cool surface  “Proof”  flame test (positive result is ignition)
 Vapors condense and the distillate (condensed liquid, purified)
The distillation of red wine can be proven through its concentration by the
drips into a reservoir separated from the original liquid
use of flame test. Proof is already used in the previous centuries because
 In simple terms, distillation involves boiling a liquid, then during those times, barter was still widely practiced. They wanted to test
condensing the gas and collecting the liquid
alcohol content and regularly tests using flame testing. An alcoholic sample
with at least 57% of alcohol by volume is capable of catching fire.

SIMPLE DISTILLATION
 Used when components have widely different boiling points
(>100℃ difference in boiling points)
 If boiling point differences are lower, then the mixture cannot
be purified  instead use fractional distillation, as an example
 Water Distillation
 Main methods to purify ocean water
 Main disadvantage: requires a lot of energy
One of the main problems in the world is the lack of clean and fresh water,
so in countries with a lot of ocean water or seawater, they can use the
distillation process to provide drinkable water. It is a main method to purify
the ocean water and its desalination  clean and fresh water supply

 Purification of Reagents and Products

 Purify products from a chemical reaction
 Purify reagents that have degraded
Boiling Stones
 Also known as boiling chips  added to a COOL liquid and Sometimes, a certain reagent or product will have impurities, so distillation
NOT when it is nearly boiling because it will result to vigorous is used to purify it further. Purify also oxidized reagents or reagents that
eruption of bubbles have already crystallized.
 Small pieces of black porous rock; cannot be reused
 Compound: silicon carbide
 Contain trapped air bubbles (added to a solvent or solution)
 Bubble out as liquid; high surface area which can be
used as sites for the solvent in the formation of
solvent bubbles  control out the movement inside
a boiling mixture

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 3: Measuring Alcohol Content
Lecturer: Mairre Louie D. Punsalan

UNDISTILLED DRINKS USP ALCOHOLOMETRIC TABLE

 Beer: 4-6% (light beers), 2-4% (malt)
 Wine: <14%
 Champagne: 10-12%
 Hard cider: ~5% (fermented apple juice)
 Mead: 10-14% (blend of water and fermented honey)
 Sake: ~16% (fermented rice)
Based on data appearing in the National Bureau of Standards Bulletin, vol.
9, pp.424-425 (publication of the National Institute of Standards and
Technology)
 http://www.uspbpep.com/usp31/v31261/usp31nf26s1_m6o00100.asp

DISTILLED DRINKS

 Gin: 35-55% (spirit made from juniper berries)

 Brandy: 35-60% (distilled wine), also called spiritus vini vitis
 Whiskey: 40-50% (spirit made from distilled, fermented grain),
also called spiritus frumenti
 Rum: ~40% (distilled drink made from fermented sugarcane or
molasses)
 Tequila: ~40% (Mexican agave plant)
 Vodka: 40% (fermented grains and potatoes)
 Absinthe: ~40-90% (variety of leaves and herbs)
 Everclear: 60%, 75.5-95% (grain-based spirit)

VACUUM DISTILLATION

 Used when the boiling points of the mixture’s components are

very high (>150℃)
 Rationale: boiling happens when the vapor pressure of a liquid
or solution equals the external or atmospheric pressure
 Thus, decreased pressure = decreased BP
 Applying vacuum source to the vacuum adapter of either simple
or fractional distillation setup
 Pressure is lowered, BP is lowered

Simple Distillation
Vs.
Vacuum Distillation

Renhart M. Salas, fRPh 2|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 4: Solubility of Drug Substances
Lecturer: Mairre Louie D. Punsalan

OUTLINE SOLUTION FORMATION

Data Sheet / Results
Post Laboratory Discussion  The formation of a liquid solution takes place in three steps:
 Solution 1. Overcoming the intermolecular forces in the solvent
 Solution Formation to give room for the solute
2. Separating the solute into its individual components
 Solubility
3. Allowing the solute and solvent to interact to form
the solution
OBJECTIVES
 To determine the solubility of different drug substances Particle size will have an effect on the solubility and solution formation

RESULTS / DATA SHEET

Descriptive Term of Solubility

Substances Distilled
Ethanol Chloroform Ether
water
Aluminum Slightly Slightly Slightly
Soluble
sulfate soluble soluble soluble
Ascorbic Freely Sparingly Sparingly Slightly
acid soluble soluble soluble soluble
Calcium Freely Freely Sparingly
Insoluble
stearate soluble soluble soluble

Samples Descriptive Term of Solubility

Benzene and chloroform Miscible
Water and alcohol Miscible Delta H represents enthalpy or heat change  both (delta H1 and H2; step
Water and phenol Partially miscible 1 and 2, respectively) are overall called as endothermic process because
Water and oil Immiscible
energy is required
Water and peppermint oil with
Partially miscible
propylene glycol
Water and benzyl benzoate with Delta H3 (step 3) will exhibit energy release  exothermic process
Partially miscible
propylene glycol
Water and ether with acetone Partially miscible SOLUBILITY EXPRESSIONS

POST-LABORATORY DISCUSSIONS  The United States Pharmacopoeia lists the solubility of drugs
SOLUTION as:
 Number of mL of solvent in which 1g of solute will
 Mixtures of two or more substances evenly distributed dissolve
throughout a single phase  “Parts of solvent required for 1 part of solute”
 Solutions are very important pharmaceutical dosage forms –
convenient to administer and easy to prepare, especially if the Parts of Solvent Required for 1
Terms
ingredients are compatible Part of Solute
Very soluble Less than 1 part
 Mixed together in such a way that the mixture has uniform
Freely soluble 1 to 10 parts
composition and particles Soluble 10 to 30 parts
 Solute vs solvent Sparingly soluble 30 to 100 parts
 Solute – substance being dissolved Slightly soluble 100 to 1,000 parts
 Solvent – dissolving medium Very slightly soluble 1,000 to 10,000 parts
Practically insoluble, or insoluble More than 10,000 parts
Solute Solvent Solution Example
Gas Gas Gas Oxygen in nitrogen Solvent-Solute Interactions
Gas Liquid Liquid Carbon dioxide in water  “like dissolves like” principle
Gas Solid Liquid Hydrogen in palladium  Polar Solvents
Liquid Liquid Liquid Ethanol in water
 Involves polarity due to dipole moment
Liquid Solid Solid Mercury in silver
Solid Liquid Liquid Salt in water
 Example: water (mixes in all proportions with
Solid Solid Solid Copper in tin (bronze) alcohol and dissolves sugars and other compounds
that are compatible with polar solvents)
Types of Solution  Nonpolar Solvents
 Saturated Solution  Unable to reduce the attraction between the ions of
 Contains the maximum amount of solute (threshold) strong and weak electrolytes (no polarity, does not
that the solvent can dissolve have the dipole moment) – cannot break the bonds
 Examples: hydrocarbons, benzene, CCl4 (carbon
 Unsaturated Solution
 Contains the less solute than the solvent tetrachloride)
 Solvent can dissolve more solute than what is  Semipolar Solvents
present in the solution  Induce certain degree of polarity in nonpolar solvent
molecules (partly polar and partly nonpolar)
 Supersaturated Solution
 Contains the more dissolved solute than is present in  Examples: ketones and alcohols (readily polarizable
a saturated solution and becomes soluble)
 Benzene can be soluble in alcohol
 Disadvantage: becomes unstable because excess
solute can crystallize in the solution because of the certain degree of plarity

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 4: Solubility of Drug Substances
Lecturer: Mairre Louie D. Punsalan

Solubility of Liquids in Liquids

Miscibility – mutual solubilities of the components in a liquid system
 Complete Miscibility
 Components mix in all proportions
 Examples: water and alcohol (both polar), glycerin
and alcohols; benzene and CCl4 (both nonpolar)
 Partial Miscibility
 Two liquid layers formed, each containing some of
the other liquid in the dissolved state
 Influenced by temperature; phase diagrams

Applications of Solubility in Pharmacy

 Gas in solids/liquids
 Examples: combination of oxygen and nitrogen,
application of carbon dioxide in water
 Liquid in liquid
 Preparation of pharmaceutical solutions involving
two or more liquids
 Alcohol and water – hydroalcoholic
solutions
 Volatile oils and water – aromatic waters
 Volatile oils and alcohols – spirits/elixirs
 Solids in liquids
 Examples: solutions such as NSS (normal saline
solution) and saltwater, simple syrup (sugar in
water)

Renhart M. Salas, fRPh 2|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 5: Factors Affecting Solubility
Lecturer: Mairre Louie D. Punsalan

OUTLINE  Forming the salt of the acid or base by raising the pH or

Post Laboratory Discussion lowering the pH will generally improve water-solubility
 Solubility  Strong acid + weak base = acidic salt
 Factors Affecting Solubility  Strong base + weak acid = basic salt
 Common-Ion Effect
COMPLEX FORMATION
OBJECTIVES
 Enhances water solubility of a molecule of a compound which
 To determine the different factors affecting solubility of drug
is normally insoluble
substances
 Chelates – a substance containing two (2) or more donor groups
which combine with a metal forming a complex
SOLUBILITY EXPRESSIONS
AMORPHOUS FORM
The United States Pharmacopeia lists the solubility of drugs as:
 Number of mL of solvent in which 1g of solute will dissolve  Amorphous solids are somehow considered supercooled liquids
 Parts of solvent required for 1 part of solute  Examples: glass, pitch, and many synthetic plastics
 Molecules are arranged in somewhat random manner  in
Part of Solvent Required for 1 Part relation to a liquid state
Terms
Solute  Tend to flow when subjected to sufficient pressure over a period
Very soluble Less than 1 part of time (difference to crystalline solids)
Freely soluble 1-10 parts  Do not have definite melting points (major difference)
Soluble 10-30 parts  More soluble*
Sparingly soluble 30-100 parts
Slightly soluble 100-1,000 parts pH
Very slightly soluble 1,000-10,000 parts
Practically
More than 10,000 parts  Adding acids to a solution in equilibrium will shift to the right,
insoluble/insoluble causing an increase in solubility.
 Adding bases to a solution in equilibrium will shift to the left,
FACTORS AFFECTING SOLUBILITY causing a decrease in solubility.
TEMPERATURE
COMMON-ION EFFECT
When it comes to physical or chemical changes, they are generally
accompanied by a transfer of energy  law of conservation of energy  Used to describe the effect on an equilibrium involving a
where energy is neither created nor destroyed during any physical or substance that adds an ion that is a part of the equilibrium
chemical processes (the entire energy in the universe is being conserved)  Ksp – equilibrium constants (solubility products) in a
heterogenous equilibria  can happen between two (2)
During a reaction, two parts are being considered: surroundings and system different phases
 System – specific portion of matter which is being studied  Several salts present in a system  ionize in the solution; salts
during an experiment with common cation/anion  concentration of the common ion
 Surroundings – everything in the universe that is not part of the  Solution containing sodium chloride and potassium chloride
system  NaCl and KCl  [Na+][K+] = [Cl-]
 Endothermic reactions: increased temperature, higher solubility Common Ions
 Heat goes inside and is absorbed by the system from  NaCl ⇌ Na+ + Cl-
the surroundings (positive)  KCl ⇌ K+ + Cl-
 Decreased temperature, lower solubility  CaCl2 ⇌ Ca2+ + 2Cl-
 Exothermic reactions: increased temperature, lower solubility  AlCl3 ⇌ Al3+ + 3Cl-
 Heat is released from the system to the surroundings  AgCl ⇌ Ag+ + Cl-
 Decreased temperature, higher solubility  Chlorine is common to almost all of the salts

Le Chatelier’s Principle
 States that if an equilibrium becomes unbalance, the reaction
will shift to restore the balance
 In common-ion effect, it might not be balanced, but because of
such principle, even if a common ion will be added to a weak
acid or a weak base equilibrium, it will still shift towards the
reactants to meet the equilibrium

COMMON-ION EFFECT ON SOLUBILITY

SALT FORMATION  Adding a common ion decreases solubility, as the reaction

 Salting-out = lower solubility  sort of precipitation, used as a
purification method to utilize reduced solubility
 Target: for substances to not dissolve
 Precipitation of large molecules such as proteins
 Salting-in = higher solubility
shifts toward the left to relieve the stress of the excess product.
 Adding a common ion to a dissociation reaction causes the
equilibrium to shift left, toward the reactants, causing
precipitation.
 Shift to left – difficulty in solubility
 Shift to right – increased or enhanced solubility

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 6: Colligative Properties of Solution
Lecturer: Mairre Louie D. Punsalan

OUTLINE When it comes to boiling point elevation, especially for electrolytes, they
Post Laboratory Discussion can dissociate in a solution, hence, the equation: △Tb = Kbm x (i) where, i
 Colligative Properties of Solution is the Van’t Hoff factor. But for most nonelectrolytes, they are being
 Vapor Pressure Lowering dissolved in water and have a value of 1 since they do not dissociate. The
 Boiling Point Elevation Van’t Hoff factor can be added to other colligative properties if the
 Freezing Point Depression substance dissociates.
 Osmotic Pressure
FREEZING POINT DEPRESSION
OBJECTIVES
Freezing Point
 To determine the different colligative properties of solution
 Temperature at which the solid and liquid phases are in
equilibrium under an external pressure of 1atm
COLLIGATIVE PROPERTIES  In general, solutions have a lower freezing point than the pure
solvent.
 Greek: “collected together”
 Depend on the relative proportion of molecules of solute and △Tf = Kf m, where
solvent  △Tf – freezing point depression
 Depend mainly on the number rather than the nature of  Kf – cryoscopic constant
constituents  m – concentration of solute
VAPOR PRESSURE LOWERING

Vapor Pressure
 Pressure of the saturated vapor above a liquid resulting from the
escape of the surface liquid molecules.
 When a nonvolatile solute is added to a volatile solvent, the
solute reduces the escaping tendency of the solvent.
 The vapor pressure of the solution is lowered proportional to
the relative number of solute molecules.

OSMOTIC PRESSURE / OSMOTIC PRESSURE LOWERING

Osmosis
 Phenomenon of solvent migration across a semipermeable
BOILING POINT ELEVATION membrane that allows only the solvent but not the solute
molecules to pass through
Boiling Point  Greek: “push” or “impulse”
 Temperature at which the vapor pressure of the liquid becomes
equal to the external atmospheric pressure Osmotic Pressure
 Bubbles produced are actually the pressure coming out from the  The pressure required to offset the movement of solvent
solvent  decreased vapor pressure, higher boiling point through a semipermeable membrane
 The boiling point of a solution containing a nonvolatile solute  The pressure required to prevent osmosis in solutions
would be higher than the pure solvent because the solute would
lower the vapor pressure of the solvent.

△Tb = Kbm, where

 △Tb – boiling point elevation
 Kb – ebullioscopic constant
 m – concentration of solute

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 7: Rates of Reaction
Lecturer: Patrick Ian Ortega

OBJECTIVES k = rate constant k = rate constant

 To identify different methods of determining the order of t = time t = time
reaction
Order Rate Law Concentration-Time Equation Half-Life
 To interpret graphical presentation of data as applied to the
0 rate = k [A] = [A]0 - kt t1/2 = [A]0 / 2k
stability of drug products 1 rate = k [A] ln[A] = ln[A]0 - kt t1/2 = ln 2 / k
 To understand the importance of reaction order and half-life 2 rate = k [A]2 1/[A] = 1/[A]0 + kt t1/2 = 1 / k[A]0
estimating shelf-life of the drug products
ZERO ORDER REACTION: RATE CONSTANTS
REACTION RATE
Time (hours) Concentration (mg/mL)
 Reaction rate for a given chemical reaction is the measure of 0 100
the change in concentration of the reactants or the change in 2 95
concentration of the products per unit time. 4 90
6 85
 X-axis = time; y-axis = concentration
8 80
10 75
Reaction Order 12 70
 The reaction order is important because it enables us to classify
specific chemical reactions easily and efficiently. k = (C0-C) / t
 Knowledge of the reaction order quickly allows us to k = (100mg/mL – 70mg/mL) / 12hr
understand numerous factors within the reaction including the k = 2.5mg/mL/hr
rate law, units of the rate constant, half-life, and much more.
FIRST ORDER REACTION: RATE CONSTANTS
Classification of Orders
1. Zero-order reaction – concentration not affected by any factors Time (hours) Concentration (mg/mL)
2. First-order reaction – concentration is affected by one factor 0 100
3. Second-order reaction – concentration is affected by two factors 4 50
8 25
ZERO-ORDER REACTION 12 12.5
16 6.25
 The rate of reaction is independent of the concentration of the 20 3.13
24 1.56
reactants in these reactions  linear graph
 A change in the concentration of the reactants has no effect on
the speed of the reaction. C = C0e-kt
1.56mg/mL = (100mg/mL)(e-k(24hr))
(1.56mg/mL) / (100mg/mL) = e-k(24hr)
FIRST-ORDER REACTION
0.0156 = e-k(24hr)  ln(0.0156) = -k(24hr)
-4.160484365 = k(-24hr)  k = -4.160484365 / -24hr
 The rates of these reactions depend on the concentration of only
k = 0.1734h-1
one reactant  slope
 In these reactions, there may be multiple reactants present, but
HALF-LIFE (t1/2)
only one reactant will be of first-order concentration while the
rest of the reactants would be of zero-order concentration.
 Amount of time needed for a reactant concentration to decrease
by half compared to its initial concentration
SECOND-ORDER REACTION
 Application in medicine: predict the concentration of a
substance over time
 When the order of a reaction is 2, the reaction is said to be a
second-order reaction  steeper slope (faster time)  Plays a key role in the administration of drugs, especially in the
elimination phase where it is used to determine how quick a
 The rate of these reactions can be obtained either from the
drug decreases in the body after it has been absorbed
concentration of one reactant squared or from the concentration
of two separate reactants.
Zero Order Reaction: Half-Life
 t1/2 = (0.5)C0 / (k)
Graph
 t1/2 = C0 / (2)(k)

t1/2 = (0.5)C0 / (k)  t1/2 = (0.5)(100mg/mL) / (2.5mg/mL/hr)  t1/2 = 20hr

t1/2 = C0 / (2)(k)  t1/2 = (100mg/mL) / (2)(2.5mg/mL/hr)  t1/2 = 20hr

First Order Reaction: Half-Life

Reaction Order
Zero Order Reaction First Order Reaction
C = -(k)(t) + C0 Log C = -(k(t) / 2.303 = log C0
ln C = -(k)(t) + ln C0
C = C0e^-(k)(t)
Where: Where:
C0 = initial concentration C0 = initial concentration
C = final concentration C = final concentration
 t1/2 = 0.693 / (k)
 t1/2 = ln 2 / (k)
t1/2 = 0.693 / (k)  t1/2 = 0.693 / 0.1734h-1  t1/2 = 3.9965hr or 4hr
t1/2 = ln 2 / (k)  t1/2 = ln 2 / 0.1734h-1  t1/2 = 3.9974hr or 4hr
EXERCISES
Using the integrated form of the rate law, determine the rate constant of a
zero order reaction if the initial concentration of substance A is 1.50M and
after 120 seconds the concentration of substance A is 0.75M.

Renhart M. Salas, fRPh 1|Pa ge

 AUF CAMP – PHARMACY DEPARTMENT
PHYSICAL PHARMACY (LABORATORY)
Exercise 7: Rates of Reaction
Lecturer: Patrick Ian Ortega

k = (C0-C) / t
k = (1.50M – 0.75M) / 120s
k = 0.00625M/s

The first-order reaction A → B, has k=8.00s–1. If the initial concentration

is 0.500M, how long will it take the final concentration to be 0.200M?

C = C0e-kt
0.2M = (0.5M)(e-8/s(t))
(0.2M) / (0.5M) = e-8/s(t)
0.4 = e—8/s(t)  ln(0.4) = -8/s(t)
-0.9162907319 = -8/s(t)  t = -0.9162907319 / -8/s
t = 0.1145s

A reaction is first order in A. If the rate constant of the reaction is 3.45 ×

10-3s–1, what is the half-life (t1/2) of the reaction?

t1/2 = 0.693 / (k)

t1/2 = 0.693 / 0.00345s-1
t1/2 = 200.8696s

Renhart M. Salas, fRPh 2|Pa ge