UNIVERSITY OF EAST ANGLIA
School of Pharmacy
Main Series UG Examination 2013-14
SPECIAL PAPER FOR:
PHARMACEUTICAL TECHNOLOGY
PHA-2FGY
Time allowed: 2 hours
Part ONE
Answer ALL questions. Use the answer grid provided for ALL of your answers.
For each of the following questions there is ONE correct answer only.
Part TWO
Answer THREE of the FOUR questions. Use a SEPARATE answer book for EACH
question.
Each question within a section has the same value. The marks distribution is shown
as a percentage for each section of the question. Answer all parts of each of the
individual questions you select.
The mark allocation for the paper is:
 Part ONE carries 30% of the total mark.
 Part TWO carries 70% of the total mark.
The following is provided: Multiple choice answer grid.
Graph paper.
This paper consists of 13 pages in total.
Notes are not permitted in this examination.
Dictionaries are not permitted in this examination.
Do not turn over until you are told to do so by the Invigilator.
Do not take this question paper out of the examinations room.
(PHA-2FGY)
Copyright of the University of East Anglia
Module contact: Dr Sheng Qi, PHA
Version 1
2
PART ONE
Answer ALL questions. Use the answer grid provided for ALL of your answers.
For each of the following questions there is ONE correct answer only.
1.
Which of the following statements is FALSE concerning the methods of
particle size determination?
(A)
(B)
Coulter counters report the equivalent volume diameter of particles
Photon correlation spectroscopy can only be used for particles that are
smaller than about 1 nm
Different particle sizing methods can give different results when the particles
are not spherical
Laser diffraction provides information about particle size distributions in a
single measurement in the 1-1000 μm range
Air-jet sieving tends to give more reproducible results than sieving by
mechanical agitation
(C)
(D)
(E)
2.
Which of the following statements is FALSE considering hoppers?
(A)
(B)
A good hopper design ensures mass flow
A hopper angle of about 20° ensures good flow for most pharmaceutical
powders
When discharging powder from a hopper, the powder flows most slowly near
the walls of the hopper
Bridging is a common problem with powders that flow poorly, while rat-holing
occurs mainly for powders that flow well
Uneven powder flow from hoppers can lead to non-reproducible doses in the
final product
(C)
(D)
(E)
3.
Which of the following statements is FALSE regarding particle size
distributions?
(A)
(B)
(C)
(D)
A bimodal distribution shows two local maxima
75% of the particles have a smaller diameter than the upper quartile
The interquartile range indicates how widely the distribution is spread
If the difference between the median and the lower quartile is less than the
difference between the upper quartile and the median, then the distribution is
negatively skewed
The mean and the median of a normal distribution have the same value
(E)
(PHA-2FGY)
TURN OVER
Version 1
3
4.
Which of the following statements is TRUE regarding the chemical stability of
drugs?
(A)
The most common chemical routes of degradation are oxidation, reduction
and photolysis
Molecules with only single bonds are more susceptible to photodegradation
than those that have multiple bonds
Hydrolysis reactions are the slowest at low pH values, typically at pH < 3
Linear amides are less stable than -lactams
The presence of chelating agents in the formulation can reduce the rate of
oxidation reactions
(B)
(C)
(D)
(E)
5.
Which of the following statements about the ICH/WHO guidelines for stability
testing is TRUE?
(A)
(B)
The United Kingdom is in Climatic Zone II
Only extrapolated long-term data are required if accelerated conditions show
no significant change
The re-evaluation date cannot be later than 6 months after the last actual data
point measured under long-term conditions
The accelerated conditions for Zones I and II are 25 °C/60% RH
Products that are intended for storage in a fridge must be tested at a storage
temperature of 0 ± 3 °C
(C)
(D)
(E)
6.
Which of the following statements is FALSE with respect to the temperature
dependence of reaction rates?
(A)
Deviation of the Arrhenius plot from a straight line can indicate a change in
reaction mechanism with temperature
Endothermic reactions proceed faster at higher temperatures, while
exothermic reactions proceed more slowly
When constructing an Arrhenius plot, the temperature should be given in
Kelvin
The frequency factor is related to the chance of productive collisions between
the reacting atoms or molecules
The activation energy can be calculated from the slope of the Arrhenius plot
(B)
(C)
(D)
(E)
7.
Which of the following statements is FALSE considering drug degradation
reactions?
(A)
(B)
Oxidation reactions often involve free radicals
The rate of photolysis reactions is influenced significantly by storage
temperature
The rate of hydrolysis reactions is influenced significantly by pH
The stages of free radical reactions are initiation, propagation and termination
Deamidation of proteins is a hydrolysis reaction
(C)
(D)
(E)
(PHA-2FGY)
Version 1
4
8.
Which of the following statements is FALSE concerning simple compressed
tablets?
(A)
(B)
(C)
(D)
(E)
Tablet shape is always an issue
They are suitable for formulating non-potent drugs
Loose powder on surface may lead to cross-contamination of products
The tablet can be compressed from either powder or granules
Drug release from these tablets can be immediate, controlled or targeted
9.
Which of the following statements is FALSE concerning film coated tablets?
(A)
(B)
(C)
(D)
(E)
Polymers are commonly used as materials for film coating
The film coat is approximately 2 to 4% (w/w) of the core tablet weight
Film coating can be used to modify the drug release
Core tablet shape is not important for film coating
Film coats can be coloured to aid tablet identification
10.
Which of the following is NOT the possible mechanism that holds the
granules together with regards to granulation?
(A)
(B)
(C)
(D)
(E)
Covalent forces
Solid bridges from deposition of binders
Solid bridges from deposition of other dissolved materials in the formulation
Surface-tension type forces from residual moisture
Van der Waals force between the particles
11.
Which of the following is FALSE concerning the wet granulation process?
(A)
(B)
(C)
(D)
(E)
Dried granules should be milled to remove large lumps
Lubricant is added to milled granules immediately before tabletting
Dried granules usually have a porous structure
The granules should be oven dried followed by air-drying for as long as
possible
Undergranulation normally results in very soft tablets
12.
Which of the following statements is TRUE concerning tabletting?
(A)
(B)
(C)
(D)
(E)
Sticking problems may be solved by increasing the quantity of the lubricant
Typical compression pressure is from 0.1 MPa to 1 MPa
Temperature will remain the same during compression
Tablet hardness is only determined by the compression pressure
Segregation can be improved by increasing granule friability
(PHA-2FGY)
TURN OVER
Version 1
5
13.
Which of the following statements is TRUE concerning film coating?
(A)
(B)
(C)
(D)
(E)
Rough surfaces can be improved by decreasing spray rate
Enteric coating material is soluble in acid media
HPMC shows good film strength
Coating suspension concentration is usually approximately 1%
The tablet bed is always heated up to 100 ºC
14.
With regards to water loss from a wet solid, which of the following statements
is FALSE?
(A)
(B)
(C)
(D)
(E)
It is most rapid during the constant rate period
It has the highest rate at the end of the process
It may involve a first and second falling rate period
It may take place from an effectively free water surface
It may take place from within the bed itself
15.
With regards to fluidised bed drying, which of the following statements is
TRUE?
(A)
(B)
(C)
(D)
(E)
It involves water loss from individual particles
It involves application of a vacuum to cause flotation
It is a slow and expensive process
It involves formation of a bed that behaves like a gas
It is used to obtain dry proteins from solution
16.
When considering the freezing of an aqueous solution of a pharmaceutical,
which of the following is FALSE?
(A)
(B)
(C)
(D)
(E)
Ice crystals may be formed
The concentration of the solute will increase
The system may form a eutectic
The system may form an amorphous dispersion
The system will freeze at 0 °C or 273 K
17.
Which of the following statements is FALSE with respect to radioactivity?
(A)
(B)
(C)
(D)
(E)
99m-Technetium emits gamma radiation with an energy of 250 keV
Beta decay can be either "positive" or "negative"
111-Indium decays to 111-Cadmium via electron capture
Alpha particles consist of two neutrons and two protons
After isomeric transition, the atomic number of the daughter nuclide is the
same as the parent nuclide
(PHA-2FGY)
Version 1
6
18.
Which of the following statements is FALSE in terms of wet granulation end
point detection?
(A)
(B)
(C)
‘Manual determination’ cannot be used on production scale
The ‘temperature rise’ method is suitable for a small scale
The ‘pressure detector’ should be placed vertically away from the chopper
blade
The temperature will be stabilised at the end point of the ‘temperature rise’
measurement
A ‘power meter’ is not suitable for modern powerful mixers
(D)
(E)
19.
Which of the following statements is TRUE with respect to
radiopharmaceuticals?
(A)
(B)
(E)
99m-Technetium has a half-life of 2 days
99m-Technetium can be attached to a range of carriers to manipulate its
biological distribution
The 99m-Technetium generator is known as a "pig"
Radiopharmaceuticals are subject to the normal "manufacture-test-use"
protocol
Radiopharmaceuticals must be autoclaved before use
20.
Which of the following statements is TRUE concerning the mixing of powders?
(A)
(B)
(C)
Agitator mixers rely mostly on the diffusive mechanism of mixing
A longer mixing time will always lead to a more uniform mixture
When testing the uniformity of a powder mixture it is best to take all samples
from the bottom of the powder bed
The variation in the percentage drug content of a drug / excipient mixture will
appear lower if larger samples are taken for analysis
Trajectory segregation leads to the accumulation of smaller particles near the
edge of the powder bed
(C)
(D)
(D)
(E)
21.
Which of the following statements about the chemical degradation of drugs is
FALSE?
(A)
(B)
(C)
(D)
(E)
Heat often can accelerate hydrolytic degradation
Trace metals can often catalyse oxidation
Ester hydrolysis is pH dependent
Amide hydrolysis can only be base-catalysed
Photolysis can be catalysed by some pharmaceutical excipients
(PHA-2FGY)
TURN OVER
Version 1
7
22.
Which of the following statements about amorphous materials is FALSE?
(A)
Amorphous materials are not stable thermodynamically, but may be stable
kinetically
Under identical experimental conditions, the dissolution rate of an amorphous
drug is higher than the dissolution rate of the same drug in a crystalline state
Plastics used for pharmaceutical packaging are usually amorphous materials
Amorphous materials become brittle when cooled below their glass transition
temperature
Amorphous materials are structurally disordered and the spatial arrangement
of molecules in them is completely random
(B)
(C)
(D)
(E)
23.
Which of the following statements is TRUE considering colonic delivery?
(A)
Transit times in the colon are dramatically different between male and female
patients
Colonic delivery is useful for conditions such as Crohn’s disease
The harsh conditions of the colon region make it an unfavourable
administration site for the systemic delivery of protein drugs
The extent of proteolysis in the colon is similar to the small intestine
Azo-polymers used for colon targeted delivery are soluble in neutral pH
(B)
(C)
(D)
(E)
24.
Which of the following statements is FALSE concerning the process of filling
powders into hard gelatin capsules?
(A)
(D)
(E)
The filling uniformity of the dependent-type fillers is less dependent on the
powder flow properties than the independent-type fillers
A dependent-type filler uses the capsule itself as a powder measure
Powder is compressed into a solid rod before it is transferred to the capsule
shell in an independent-type filler
The volume of the dosing tube of an independent-type filler is adjustable
The process must be conducted in a low humidity environment
25.
Which of the following statements is TRUE considering softgel capsules?
(A)
(B)
(C)
(D)
(E)
Softgel capsules can only be mono-coloured
Softgel capsules are made from high bloom gelatin
Glycerol can be used as a plasticiser in softgel capsule shells
Softgel capsule shells contain 20% water
Softgel capsules are mostly used for controlled drug delivery
(B)
(C)
(PHA-2FGY)
Version 1
8
26.
Which of the following statements is TRUE concerning packaging design and
labelling?
(A)
(B)
(C)
(D)
(E)
The batch number is not required on the packaging
Legal category POM refers to pharmacy only medicine
The strength of the medicine is required to be labelled on the primary packing
only
The labelling must follow official regulation requirements
Sophisticated packaging design is encouraged for POM medicines
27.
Which of the following statements is FALSE concerning tamper-proofing?
(A)
(B)
(C)
(D)
(E)
Foil seals for creams can provide tamper-proofing for the product
Push-through lidding of blister packs is good for tamper-proofing
Seals on the secondary packaging can enhance tamper-proofing
Metal strips are good for tamper-proofing
Tamper-proofing is more important in POM than OTC products
28.
Which of the following statements is TRUE concerning tablet specifications?
(A)
Under the content uniformity specification, 20 tablets should be tested at the
stage 1 test
Stage 2 of the pharmacopoeial "Content Uniformity" specification allows a
range of 75 to 125% around the mean value on the 20 tested tablets
A batch passes the content uniformity test, if all of tablets tested have values
between 85 and 115% of the mean
The BP specifications for the friability test allow up to 2% tablet weight loss
The same general pharmacopoeial specifications apply to all tablet and
capsule products
(B)
(C)
(D)
(E)
29.
Which of the following statements is FALSE concerning the polymers used for
oral controlled drug delivery?
(A)
(B)
(C)
(D)
(E)
Film coats made from azo-polymers are used to provide colonic targetting
HPMC may be used as a matrix former for monolithic devices
Eudragit S is a polymer for enteric coating and is soluble at pH 4-6.
Chitosan is a polymer with mucoadhesive properties
Ethylcellulose is commonly used to make drug release rate limiting
membranes
(PHA-2FGY)
TURN OVER
Version 1
9
30.
When preparing hard gelatin capsule shells, which of the following statements
is TRUE?
(A)
The gelatine is first dissolved in cold deionised water during capsule
manufacture
The hard gelatin shells are made from dipping pins into a concentrated gelatin
solution then followed by drying
A size 3 capsule shell has approximately a 3 ml volume
Titanium dioxide is often used as colourant for producing red capsules
Hard gelatin capsule shells can only be used for solid powder filling
(B)
(C)
(D)
(E)
END OF PART ONE
(PHA-2FGY)
Version 1
10
PART TWO
Answer THREE of the FOUR questions. Use a SEPARATE answer book for EACH
question.
31.
Answer ALL parts (a) to (e).
As an industrial pharmacist, you are studying the solid-state behaviour of new drugs.
One drug is found to exist in two polymorphic crystalline forms.
(a)
Define the term ‘polymorphism’, as used in this context.
[10%]
(b)
Discuss the importance of polymorphism to the formulation of solid oral
dosage forms.
[25%]
(c)
The two polymorphs are found to have different angle of repose and tap
density values. Explain the principles behind these testing procedures, including any
relevant diagrams and equations. Why are these tests commonly used during the
formulation of solid oral dosage forms?
[25%]
(d)
The two polymorphs are found to have different particle size distributions.
Explain the importance of particle size and particle size distribution for the
formulation of solid oral dosage forms.
[20%]
(e)
Explain the principles of sieve analysis as a means of assessing the particle
size distribution of a powder. Include in your answer a consideration of the data
processing required.
[20%]
(PHA-2FGY)
TURN OVER
Version 1
11
32.
Answer ALL parts (a) to (c).
You are a formulation scientist developing a controlled-release tablet formulation
targeted for colon drug delivery intended for once daily use.
(a)
Describe the rationale behind the colon-targeted drug delivery. Discuss the
advantages and disadvantages.
[40%]
(b)
Describe different formulation approaches for achieving colon-targeted drug
delivery.
[40%]
(c)
Describe an experiment that could be performed to determine the transit of
controlled-release oral formulations in human volunteers.
[20%]
(PHA-2FGY)
Version 1
12
33.
Answer BOTH parts.
You work in the "Formulation and Process Development" department of a
pharmaceutical company and are currently developing an immediate-release soft
gelatine capsule formulation of a new poorly water-soluble drug. The oral absorption
data of the new soft capsules showed dramatic enhancement of absorption in
comparison to the directly compressed tablet formulation. The intended capsule
strength of the drug is 30 mg and the capsule weight is 500 mg.
(a)
Explain the possible reason for enhanced oral absorption of the drug in the
soft gelatin capsule in comparison to tablet formulations.
[30%]
(b)
During the manufacture of the capsules, the following data set on one batch of
the uncoated capsules is listed in the table below.
Test
Capsule weight uniformity
(mg)
Content uniformity
(mg)
Disintegration time at 37C
(mins)
Results
495, 498, 505, 501, 506, 494, 509, 493, 501, 503,
505, 506, 494, 498, 506, 484, 502, 509, 497, 498
29.0, 25.6, 28.8, 26.6, 29.7, 31.3, 30.3, 28.9, 29.6,
30.1
13, 19, 15, 15, 14, 22, 18, 17, 16, 12
(i)
Briefly describe the BP method for measuring the weight uniformity of
soft gelatine capsule products. Comment on whether the batch meets the BP
specification for capsule weight uniformity.
[25%]
(ii)
Briefly describe the BP method for measuring the content uniformity of
soft gelatine capsule products. Comment on whether the batch meets the BP
specification for capsule content uniformity.
[25%]
(iii)
Briefly describe the BP method for measuring the disintegration time of
soft gelatine capsule products. Comment on whether the batch meets the BP
specification for capsule disintegration time.
[20%]
(PHA-2FGY)
TURN OVER
Version 1
13
34.
Answer ALL parts (a) to (d).
Stress-testing of the drug nitazoxanide by intensive UV irradiation gave the following
results. The main route of photodegradation was identified as:
Nitazoxanide
The concentration of the drug in a solution preparation during irradiation was
measured to be:
Time / h
0
1
2
3
4
Concentration / ( μg mL-1 )
19.4
16.6
13.8
10.7
7.9
(a)
Explain the term ‘stress testing’ and its role in the development of
pharmaceutical formulations.
[20%]
(b)
Determine the reaction order by plotting the appropriate linear graph.
Determine the reaction rate constant (k) and the half-life of the drug from the graph.
Show your working.
[40%]
(c)
When stored in the dark, nitazoxanide solutions degrade by a different route.
Give the most likely degradation reaction.
[10%]
(d)
Suggest strategies to minimise the degradation of nitazoxanide, taking into
account both its photodegradation and the reaction discussed in part (c).
[30%]
END OF PAPER
(PHA-2FGY)
Version 1