PHYSICAL PHARMACY LABORATORY: PRELIM

EXPERIMENT 1: SPECIFIC GRAVITY DETERMINATION OF LIQUIDS

The specific gravity of a liquid of known weight and volume may be calculated by the equation:

If 54.96 mL of an oil weighs 52.78 g, what is the specific gravity of the oil?
54.96 mL of water weighs 54.96 g

PYCNOMETER or Specific Gravity Bottle

A pycnometer is a special glass bottle used to determine specific gravity.
Pycnometers are generally available for laboratory use in volumes ranging from 1
mL to 50 mL.Pycnometers have fitted glass stoppers with a capillary opening to
allow trapped air and excess fluid to escape. Some pycnometers have thermometers
affixed in order to relate the specific gravity, as determined, with temperature.
In using a pycnometer, it is first weighed empty and then weighed again when
filled to capacity with water. The weight of the water is calculated by difference.
Since 1 g of water equals 1 mL, the exact volume of the pycnometer becomes known. Then, when any other
liquid subsequently is placed in the pycnometer, it is of equal volume to the water, and its specific gravity may
be determined.
A 50 mL pycnometer is found to weigh 120 g when empty, 171 g when filled with water, and 160 g when
filled with an unknown liquid. Calculate the specific gravity of the unknown liquid.

PHYSICAL PHARMACY LABORATORY: PRELIM

HYDROMETER
A hydrometer is an instrument used to measure the density of a liquid as compared to that of water.
Hydrometers usually consist of a calibrated glass tube ending in a weighted glass sphere that makes the tube
stand upright when placed in a liquid.

The greater the density, the tighter or closer the molecules are packed inside the substance.
Therefore, the greater the density / specific gravity of a liquid the higher a hydrometer will be buoyed by
it.

Fill your hydrometer jar about with the liquid you wish to test. Insert the hydrometer slowly. Do not drop it
in! Now give it a spin with your thumb and index finger, this will dislodge any bubbles that may have formed.
Once the hydrometer comes to a rest, observe the plane of the liquid surface. Your eye must be horizontal to
this plane. The point at which this line cuts the hydrometer scale is your reading.
TYPES OF HYDROMETER:
Specific Gravityhydrometers can be used for almost any liquid. Specific Gravity is a dimensionless unit
defined as the ratio of density of the material to the density of water. If the density of the substance of
interest and the reference substance (water) are known in the same units (e.g., both in g/cm3 or lb/ft3),
then the specific gravity of the substance is equal to its density divided by that of the reference substance
(water =1 g/cm3)
Baumehydrometers are calibrated to measure specific gravity on evenly spaced scales; one scale is for
liquids heavier than water, and the other is for liquids lighter than water.
These two scales, one for liquids lighter than water and one for liquids heavier than water, were
developed by the French chemist Antoine Baum in 1768. It is widely used in industrial
chemistry, pharmacology, sugar refining and other industries. The two scales are expressed below
as:
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for liquids lighter than water and

for liquids heavier than water and

Note: Many literature sources present the above equations with the specific gravity reference
temperatures being 20C, which ignores the small difference between specific gravities at 60 F and
20 C.

Brix (BX) hydrometer is for determining the percentage of weight by sucrose. One degree Brix is 1 gram of
sucrose in 100 grams of solution and represents the strength of the solution as percentage by weight (%
w/w) (strictly speaking, by mass). If the solution contains dissolved solids other than pure sucrose, then the
Bx only approximates the dissolved solid content. The Bx is traditionally used in the wine, sugar, fruit
juice, and honey industries.
It is expressed as:

and

MOHR/WESTPHAL BALANCE
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The principle of the balance is based on the known buoyancy of a reference glass body.

1 Foot with adjustment screws

2 Metal frame with adjustable height
3 Balance beam with notches
4 Plummet (glass cylinder with thin Platinum
wire)
The beam of the balance is balanced with the plummet (glass cylinder hanging on a thin platinum wire
attached to a hook on the beam) in air using the adjustable screws on the foot.

When adjusted, the index pointer on the end of the beam lines up with the point on the frame.

The plummet is then completely immersed in the unknown liquid, and the system is rebalanced, using a
series of riders on the nine equally spaced notches on the beam, thus specifying the value of the added
mass for each decimal place.

This gives the buoyant force of the liquid relative to water, and hence the density, which may be
obtained to three decimal places.
SPECIFIC GRAVITY READING:

Notch number gives the

numerical value
Weights indicates the placement
of the numerical value

SUBSTANCE

SPECIFIC GRAVITY

Clove oil

1.038-1.060 (25oC)

Ethyl alcohol

Not above 0.816 (15.56oC)

Liquid petrolatum

0.860-0.905

Syrup

1.313

Glycerin
WEIGHTS:
5g
1
__/1
0.5g
0.1
__/10
0.05g
0.01
__/100
0.005
0.005
__/100

Not below 1.249

EXPERIMENT 2: MELTING POINT DETERMINATION

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The temperature at which a solid melts and becomes a liquid is the melting point. Since this requires that
the intermolecular forces that hold the solid together have to be overcome, the temperature at which melting
occurs will depend on the structure of the molecule involved - an example of the relationship between structure
and properties. Hence, different compounds tend to have different melting points.
A pure, nonionic, crystalline organic compound usually has a sharp and characteristic melting point
(usually 0.5-1.0oC range). A mixture of very small amounts of miscible impurities will produce a depression of
the melting point and an increase in the melting point range. Consequently, the melting point of a compound is
a criterion for purity as well as for identification.
The melting point of an organic solid can be determined by introducing a tiny amount into a small capillary
tube, attaching this to the stem of a thermometer centred in a heating bath, heating the bath slowly, and
observing the temperatures at which melting begins and is complete. Pure samples usually have sharp melting
points, for example 149.5-150oC or 189-190oC; impure samples of the same compounds melt at lower
temperatures and over a wider range, for example 145-148oC or 186-189oC.

Melting Ranges
Although there should be a single temperature at which a pure solid and a liquid are in equilibrium,
most samples appear to melt over a small temperature range. This happens because, with capillary or block
melting points, the temperature of the bath or block rises a little during the time it takes the sample to melt.
The presence of impurities in the sample can also cause the sample to melt over a range of temperatures.
Thus, the melting point will usually be reported as a melting range, the temperatures between which the
sample melted.
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The Melting Point as a Criterion of Purity
A dilute solution of a liquid begins to freeze at a temperature somewhat lower than the freezing point
of the pure liquid. The presence of an impurity causes a reduction of the freezing point of the sample. As
the pure solvent crystallizes from solution, the concentration of the impurity must increase and the freezing
point of the solution must fall. Thus, a sharp melting point (actually, a melting range of less than about 1C)
is often taken as evidence that the sample is fairly pure, and a wide melting range is evidence that it is not
pure.
The Melting Point as a Means of Identification and Characterization
If two samples have different melting points, their molecules must differ either in structure or in
configuration. They must be either structural isomers or diastereomers. If the melting points of two samples
are the same, the structures of their molecules must be the same, although they might have enantiomeric
configurations. These statements apply only to pure substances, and do not take into account the fact that
some substances can exist in different crystalline forms that have different melting points.
Mixture Melting Points
Mixtures of different substances generally melt over a range of temperatures, and melting is usually
complete at a temperature that is below the melting point of at least one of the components. Thus, the
nonidentity of two substances of the same melting point can often be established by determining that the
melting point of a mixtures of the two is depressed. If each individual sample melts "sharply" (and at the
same temperature, of course), and if an intimate mixture of the two, made by rubbing approximately equal
amounts together, melts over a wide range, the two substances are not the same.
Usually, however, you wish to establish the identity rather than the nonidentity of two samples, so it is
unfortunate that the converse is not always true: the absence of a depression of the melting point or of a
wide melting range of the mixture is not certain evidence that the two substances are identical in molecular
structure and configuration.
Melting Point and Molecular Structure
Systematic variations of melting point with changes in structure are not as obvious or predictable as are
the variations in boiling point.
Molecular Weight
Although melting points do generally increase with increasing molecular weight, the first members of
homologous series (compounds differing by only a CH2) often have melting points that are considerably
different from what would be expected on the basis of the behavior of the higher homology In some
homologous series of straight-chain aliphatic compounds, melting points alternate: the melting point of
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successive members of the series is higher or lower than that of the previous member, depending on
whether the number of carbon atoms is even or odd. Sometimes, as with the normal alkanes, the melting
points of successive members of the series always increase, but by a larger or smaller amount, depending
upon whether the number of carbons is even or odd.
Polarity
As with boiling points, compounds with polar functional groups generally have higher melting points
than compounds with nonpolar functional groups. In contrast to the case with boiling points, highly
branched or cyclic molecules (relatively symmetrical molecules) tend to have higher melting points than
their straight-chain isomers. The combined effects of branching or the presence of rings, then, are to reduce
the range of temperature over which the liquid can exist at a vapor pressure of less than 760 Torr. In
extreme cases, a liquid range does not exist at a vapor pressure of less than 760 Torr; at atmospheric
pressure, the substance will sublime without melting. Hexachloroethane and perfluoro-cyclohexane behave
in this way.

EXPERIMENT 3: REFRACTIVE INDEX DETERMINATION OF VOLATILE OILS

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Introduction:
A refractometer measures the extent to which light is bent (i.e. refracted) when it moves from air into a sample
and is typically used to determine the index of refraction (aka refractive index or n) of a liquid sample.
The refractive index is a unitless number, between 1.3000 and 1.7000 for most compounds, and is normally
determined to five digit precision. Since the index of refraction depends on both the temperature of the sample
and the wavelength of light used these are both indicated when reporting the refractive index:

The italicized n denotes refractive index, the superscript indicates the temperature in degrees Celsius, and the
subscript denotes the wavelength of light (in this case the D indicates the sodium D line at 589 nm).
The refractive index is commonly determined as part of the characterization of liquid samples, in much the
same way that melting points are routinely obtained to characterize solid compounds. It is also commonly used
to:

Help identify or confirm the identity of a sample by comparing its refractive index to known values.
Assess the purity of a sample by comparing its refractive index to the value for the pure substance.

Determine the concentration of a solute in a solution by comparing the solution's refractive index to a
standard curve.

Refractive index
The speed of electromagnetic waves in vacuum, c=2,99792458108 m/s, is one of the most important
constants in physics. A human eye is able to detect electromagnetic waves in a range from 360 nm (violet
color) to 750 nm (red color). It is called a visible range of light.
When light waves travel through a medium (optical medium), its electric part interacts with the electrons
of that medium, causing them to vibrate. The electrons of the medium thus become radiating light waves as the
secondary sources. However, the speed of new waves, v, changes accordingly to the optical properties of the
particular medium. It is always smaller than the speed of light in vacuum, v<c. All materials are characterized
by their ability to slow down the light waves, known as optical refractive index n

PHYSICAL PHARMACY LABORATORY: PRELIM

The refractive index is a unitless parameter, equal to 1 for a vacuum and larger than 1 for any other
material (e.g. n=1.33 for water). The speed of light in air is only slightly less than c, resulting into the refractive
index of 1.0003. Typically, it is truncated to 1. The difference between a light speed in different media results
into the change of direction along which the light propagates, refraction (Fig. 1). Refraction occurs when the
light passes from one medium to a medium with a different index of refraction, except the light that approaches
the boundary between the two media perpendicularly. Accordingly to the properties of an optical medium, some
portion of light approaching the interface at an incident angle a is reflected back to the first medium while the
rest propagates into the other medium at an angle of refraction b. The angles of incident, reflection and
refraction are defined as angles between the particular ray and the interface normal (see Fig. 1).

Note, that the reflection angle is always equal to the incident angle.

On the other hand, the refractive angle is determined by the Snell's law

where n1 is the refractive index of medium 1 and n2 is the refractive index of medium 2.
It is possible to define an optical density for the media of different refractive indices.
Medium A has a higher optical density than medium B, if

its

refractive index is higher than that of medium B.

According to the Snell's law, the light ray is "bending

towards

the normal" (b<a), if it enters the medium with a higher

optical

density (Fig. 1). When it enters the medium with a lower

optical

density, it is "bending away from the normal" (b>a).

Refractive index can be measured by the
refractometer. We will use the double prism system
the Abbe's refractometer, shown in Fig. 2. It consists of
optical prisms (illuminating and refracting) with the thin

called
Fig. 1. Refraction of light

the two
layer of

a liquid sample between them. The measuring prism is made of a glass with a high refractive index (n2>1,75),
which allows this refractometer to measure refractive indices up to n1<1.75. The light enters the refractometer
from the left side of the illuminating prism at many different angles. The bottom part of this prism (AB') is rough,
i.e. it consists of many small areas oriented in different directions. As such, this surface can be imagined as a
source shining the light into all directions. Part of this light passes through the sample into the refracting prism,
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where the biggest possible angle of incident, amax, corresponds to the ray that propagates from point A to
point B (Fig. 2). According to the Snell's law, the refraction of this ray is then described by the maximum angle
of refraction bmax. All other rays enter the refracting prism at smaller angles and thus end up to the left of point
C.
Consequently, detector located at the bottom of the refracting prism detects the illuminated region to the left of
point C and a dark region to the right of this point. Since the maximum angle, amax, and the refractive index of
the refracting prism, n2, are known constants, it is straightforward to determine the refractive index of a
measured liquid, n1. The interface between an illuminated and dark region (position of point C) changes as a
function of angle bmax, which is different for samples with different refractive indices n1. The simple readout
from the scale of refractometer then provides the refractive index directly, or it can be readily determined using
a conversion table.

Fig. 2.The schematic of the Abbe's refractometer.

The refraction index depends on the wavelength of light, because the speed of light waves depends on
their wavelength. Light of different colors (different wavelengths) is bending at different angles even if it comes
at the same angle of incident(dispersion). As a result, the white light, that comprises all the wavelengths,
produces a rainbow after passing through the optical prism (or droplets of moisture in the atmosphere).
However, despite the beauty of a rainbow, this is an unwanted effect in refractive index determination. It
causes the smearing of an interface between the illuminated and dark regions in the Abbe's refractometer. To
increase the precision of a measurement, it is therefore preferable to use a monochromatic light (light of a
single wavelength). The most commonly used source is sodium light of a wavelength equal to 589 nm.
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The refractive index depends also on the density of the measured sample, which is affected by its
temperature. Typically, refractive index decreases with the decreasing density (increasing temperature). The
measurement of a refractive index is therefore reported together with the temperature and the wavelength of
light used. Symbol 20D n then represents the refractive index measured at t=20 C using the sodium line D
light (low pressure sodium lamp).
Note:

The speed of light in a substance is slower than in a vacuum since the light is being absorbed and
reemitted by the atoms in the sample. Since the density of a liquid usually decreases with temperature, it is
not surprising that the speed of light in a liquid will normally increase as the temperature increases.

Thus, the index of refraction normally decreases as the temperature increases for a liquid.
For many organic liquids the index of refraction decreases by approximately 0.0005 for every 1 C increase
in temperature. However for water the variation is only about -0.0001/C.

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ABBE REFRACTOMETER

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EXPERIMENT 4: BUFFER SOLUTIONS

Buffers
Theory:
A buffer is a solution that resists change in pH upon addition of acid, addition of base, and upon
dilution. Buffer solutions contain significant quantities of both partners of a Bronsted-Lowry conjugate acidbase pair. To understand how buffers accomplish this, it will be necessary to review some Bronsted-Lowry
acid-base chemistry.
According to Bronsted and Lowry an acid is a proton (an H+ ) donor. A base is definedas a substance
that can accept a proton. When an acid gives up a proton, a species that can accept a proton, a base, is
formed from the acid. That base is called the conjugate base of the acid.
HA -----------------------> H+ + A Acid

Conjugate Base

For example, acetic acid ( CH3COOH) loses a proton to form acetate (CH3COO - )which will be the
conjugate base. The acetate is a potential proton acceptor and, as such,it must be considered to be a base.
The acetate is considered to be the conjugate base of acetic acid, and acetic acid is considered to be the
conjugate acid of the base, the acetate ion. In a similar manner sodium bicarbonate (HCO3 - ) may lose a
proton to become sodium carbonate (CO3-2 ).. Sodium bicarbonate is the acid, and sodium carbonate is the
conjugate base. Finally, note the sodium dihydrogen phosphate and disodium monohydrogen phosphate
system. The sodium dihydrogen phosphate (H2PO4- ) is the proton donor, the acid, while its product, disodium
monohydrogen phosphate (HPO4 -2), is the proton acceptor and hence, the conjugate base.
Although we frequently represent the proton in water (aqueous) solution as H+, actuallythe proton
combines with water to form ions like H3O + , H5O2+ , and H7O3+. The main form is the hydronium ion,
H3O+.
Acids and bases can be divided into two broad categories, strong and weak. Strong acid lose their
acidic protons virtually 100 % and strong bases accept protons virtually 100 %.Weak acids and bases lose and
gain protons respectively less than 10 %. All the acids and bases described above would be considered to be
weak.
To form a buffer one may mix a weak acid with its conjugate base or a weak base with itsconjugate
acid. The mixture that results will resist any attempt to change the pH and willact as a buffer. In this theory we
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will refer to a buffer as a mixture of a weak acid and itsconjugate base. Suppose we mix the acetic acid
(CH3COOH) with its conjugate base, acetate, (CH3COO - ) . There will be present in the mixture both an acid
and a base that would tend to react with any added acid or base.
Suppose that a source of H+ is added. The conjugate base, acetate, will react as follows:
H+ + CH3COO - ---------> CH3COOH
Suppose that a source of OH - is added. The weak acid, acetic acid, will react as
follows:
CH3COOH + OH - -------> H2O + CH3COO In either case, the invading species is not allowed to change the pH of the solution.
One must use weak acids in buffers so the conjugate bases will have a tendency to react with protons.
If a strong acid were mixed with its conjugate base, the conjugate base would have no tendency to react with
protons.( A strong acid reacts 100 % to lose its protons, so there must be no tendency of the reaction to go in
reverse to pick up protons.)This would leave the solution susceptible to attack by protons.
In this experiment you will make several mixtures of weak acids with their conjugatebases to create
buffers. You will test these by adding both acid and base to the mixtures. You will also test distilled water and
single components of the buffers in the absence of their conjugates to see how they hold up to the challenge of
added acid and base.
When working with a buffer one must be concerned with two major questions:
1) Over what pH range will the buffer work and
2) What is the capacity of this buffer to resist pH change?

Buffers do not buffer only at a pH of 7.0. Some do, but others buffer in the acidic rangeof pH's, and
others buffer in the basic range of pH's. The initial pH of a buffer dependsupon two factors:
1) the strength of the weal acid or weak base and
2) the ratio of weak acid to its conjugate base.

Considering the first fact, the stronger the weak acid the more acidic will be the pH of the buffer;
The weaker the weak acid the more basic the initial pH.

After the range is determined by the strength of the weak acid component, the actual initial pH is
determined by the ratio of the weak acid to the conjugate base.
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The pH of the buffer will be a bit more basic if more of the conjugate base is present than the weak
acid, and it will be a bit more acidic if more of the weak acid is present than the conjugate base.

The buffer capacity depends upon two factors:

1.) Concentration of the buffer

In general the more concentrated the buffer, the more ingredients areavailable to attack added
H+ and OH - ions.

2.) What is beingadded to the buffer and how much of each component, acid and conjugate base, is available
to react.

Suppose that a buffer had 100 times as much acetic acid as it hadacetate. This buffer could
resist a challenge by base because there would be plenty of acetic acid to react with the base. It
would not, however, be able to resist an attack by acid, because there would be relatively little
acetate to react with the acid.

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