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Physical Pharmacy
Q1) Explain the following:
Babylon University / College of Pharmacy
Final exam.
1st attempt
2nd semester 2010/2011
(10 mark)
a) A small displacement of highly bound drugs to plasma proteins may lead to toxicity.
b) None of the measurements for determining particle size are truly direct methods.
c) In most cases, -cyclodextrin can not be used in pharmaceutical dosage forms.
d) Some vessels containing chemical substances should be immersed in ice before opening.
Q2)
(5 mark)
a) Discuss the effect of geometric isomerism in the formation of chelates complexes.
b) What is the equivalent spherical diameter, with examples?
Q3)
(5 mark)
Higuchi and Zuck investigated the complex formation between caffeine and butyl paraben by the
solubility method. The results at 15°C were: Solubility of butyl paraben when no caffeine is
present was 0.58×10−3 M. The concentration of added caffeine 6.25×10−2 M. Solubility of butyl
paraben when above amount of caffeine is present 3.72×10−3 M. Assuming that the complex has a
stoichiometric ratio of 1:1, compute the stability constant, K.
Q4)
(5 mark)
a) Define transference number and mention the factors affecting it.
b) In a certain electrical cell, the current carried by cations was three folds of that carried by
anions, and the total current of the cell was 480 ohm. Calculate the transference numbers.
Dr. DHAFIR QAHTAN SAEED
Good Luck
Answers for final exam
Q1) Explain the following:
(10 mark)
a) A small displacement of highly bound drugs to plasma proteins may lead to toxicity.
In many cases, the free drug concentration, rather than the total concentration in plasma, is correlated to the effect. Drug displacement
from drug-protein complex can occur by direct competition of two drugs for the same binding site and is important with drugs that are
highly bound (>95%), for which a small displacement of bound drug can greatly increase the free drug concentration in the plasma.
Drug bound 95% then free is 5, if another 5 % is displaced the free active form will be 10% which mean that the concentration of the free
drug increased by 100% which may lead to toxicity, while the drug that are moderately bound to protein , for example 50% then free is
50, if 5 % is displaced then free active form will be 55% which mean that the concentration of the free drug increased by 10%
b) None of the measurements for determining particle size are truly direct methods.
Many methods are available for determining particle size. Only those that are widely used in pharmaceutical practice and are typical of a
particular principle are presented like Microscopy, sieving, sedimentation, and the determination of particle volume None of the
measurements are truly direct methods.
Although the microscope allows the observer to view the actual particles, the results obtained are probably no more "direct" than those
resulting from other methods because only two of the three particle dimensions are ordinarily seen. The sedimentation methods yield a
particle size relative to the rate at which particles settle through a suspending medium, a measurement important in the development of
emulsions and suspensions. The measurement of particle volume, using an apparatus called the Coulter counter, allows one to calculate an
equivalent volume diameter. However, the technique gives no information as to the shape of the particles. Thus, in all these cases, the size
may or may not compare with that obtained by the microscope or by other methods.
c) In most cases, -cyclodextrin can not be used in pharmaceutical dosage forms.
Unfortunately, the water solubility of -cyclodextrin (1.8 g/100 mL at 25°C) is often insufficient to stabilize drugs at therapeutic doses,
and is also associated with nephrotoxicity when cyclodextrin is administered by parenteral routes. The relatively low aqueous solubility of
the cyclodextrins may be due to the formation of intramolecular hydrogen bonds between the hydroxyl groups, which prevent their
interaction with water molecules.
Q2)
(5 mark)
a) Discuss the effect of geometric isomerism in the formation of chelates complexes.
Ions such as Cu and Ni, which form square planar complexes, and Fe and Co, which form octahedral complexes, can exist in either of two
geometric forms. As a consequence of this isomerism only cis-coordinated ligands-ligands adjacent on a molecule will be readily replaced
by reaction with a chelating agent. Vitamin B 12 and the hemoproteins are incapable of reacting with chelating agents because their metal is
already coordinated in such a way that only the trans-coordination positions of the metal are available for complexation. In contrast, the
metal ion in certain enzymes, such as alcohol dehydrogenase, which contains zinc, can undergo chelation, suggesting that the metal is
bound in such a way as to leave two cis positions available for chelation.
b) What is the equivalent spherical diameter with examples?
The size of a sphere is readily expressed in terms of its diameter, however, as the degree of asymmetry of particles increases, so does the
difficulty of expressing size in terms of a meaningful diameter. Under these conditions, there is no one unique diameter for a particle.
Recourse must be made to the use of an equivalent spherical diameter, which relates the size of the particle to the diameter of a sphere
having the same surface area, volume, or diameter. Thus, the surface diameter, ds, is the diameter of a sphere having the same surface area
2
as the particle in question. The diameter of a sphere having the same volume as the particle is the volume diameter, dv, whereas the
projected diameter, dp, is the diameter of a sphere having the same observed area as the particle when viewed normal to its most stable
plane. The size can also be expressed as the Stokes diameter, dst, which describes an equivalent sphere undergoing sedimentation at the
same rate as the asymmetric particle.
Q3)
(5 mark)
Higuchi and Zuck investigated the complex formation between caffeine and butyl paraben by the
solubility method. The results at 15°C were: Solubility of butyl paraben when no caffeine is
present was 0.58×10−3 M. The concentration of added caffeine 6.25×10−2 M. Solubility of butyl
paraben when above amount of caffeine is present 3.72×10−3 M. Assuming that the complex has a
stoichiometric ratio of 1:1, compute the stability constant, K.
caffeine + butyl paraben = caffeine-butyl paraben
K
[caffeine  butylparaben]
[caffeine][butylparaben]
[caffeine-butyl paraben]complex = 0.00372-0.00058 = 0.00314
[caffeine]=0.0625-0.00314= 0.0593
[butyl paraben] = 0.00058
K
[caffeine  butylparaben]
0.00314
0.00314


 91
[caffeine][butylparaben] 0.0593  0.00058 0.0000343
Q4)
(5 mark)
a) Define transference number and mention the factors affecting it.
Transference number: The fraction of total current carried by the cations or by the anions is known as the transport or transference number
t+ or t–
The transference numbers are related to the velocities of the ions, the faster-moving ion carrying the greater fraction of current. The
velocities of the ions in turn depend on hydration as well as ion size and charge. Hence, the speed and the transference numbers are not
necessarily the same for positive and for negative ions.
b In a certain electrical cell, the current carried by cations was three folds of that carried by anions,
and the total current of the cell was 480 ohm. Calculate the transference numbers.
currentcarriedbycations 3
    360ohm
480ohm
4
t 
Current carried by cations 360

 0.75
Total current
480
t  t  1
t  1  t  1  0.75  0.25
3