Subject Code: PFM714 Duration: Approx.3 Hours Instructor: V. Shulman
Student Name:_________ ________________________
Student Number_____________
1.
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2.
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3.
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Question 1
List the three types of main processes
used in the Pharmaceutical Industry
Give a very brief description of the
process.
a)
Most difficult. Wet Granulation- The Mix
is wetted, made into a granule, dried, resized, and finally
remixed with additional lubricant and disintegrant
(Brief
Description).
b)
Next in degree of Difficulty. Dry Granulation-
‘Sticks’/wafers of chilsonate made by compaction using rollers are passed
through a oscillator/mill to make granules
(Brief Description).
c)
Easiest. Direct compaction- materials
are simply passed through a screen, and then blended without lubricant for 75%
of the mixing time. (recirculate is necessary). Afterwards, lubricant
is added, and eventually compressed
(Brief Description).
(6)
Question
2
What 3
parts of the tablet press that control the flow of the granulation to
the die?
a)
Hoppers
b)
Feed frames
c) Scrapers
c) d) The tablet press
(turrent and cams/controls) (3)
Question
3
a) In your
own words how are tablets compressed?
___Granules are fed into
feed frames by hoppers, and these feed frames
uses paddles to force granulations into the dies.
Scrapers then scrap off excess granules from the top of each die. Cams with
pressure sensors and tracks for upper and lower punches to be
filled and moved to a
compression roller, thus creating a compressed tablet. _____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
(5)
List the 7
stages of compression in detail, & state what part of the Tablet
press is responsible for each stage of the compression process.
Compression stages
1. __The cavity in the die is created
by the lower punch pulled down by the fill cam . Fill cam
size determines the depth of fill. ________________________________________________________________________________________________________________________________________________________________________________________________________________
2. _Suction created by the punch moving downward,
gravity, and/or paddles forcing granulation into the die (close feed frames)
fills the die. _________________________________________________________________________________________________________________________________________________________________________________________________________________
3. _The weight adjustment ramp/assembly and head corrects the volume of granulation into the die cavity. The spring loaded scraper then removes materials that escapes from the feed frame._________________________________________________________________________________________________________________________________________________________________________________________________________________
4. _Height of the fill die is then moved below the die bore chamber by having the lower punch moving along the pull-down cam. _________________________________________________________________________________________________________________________________________________________________________________________________________________.
5. _Precompression rollers expels air from between the granules and the die-making a soft tablet_________________________________________________________________________________________________________________________________________________________________________________________________________________
6. ____the main compression rollers then compresses the granules into a tablet______________________________________________________________________________________________________________________________________________________________________________________________________________
7. the ejection cam then pushes the punch tip to be 002” above the die table and the take off blade deflects the finished tablet down the discharge chute__________________________________________________________________________________________________________________________________________________________________________________________________________________ (21)
Question
#4
Most Hard
Gelatin Capsules can be made on automatic equipment using the active - plus
2 excipients / inactives, Name them and the function they play in the
formulation.
1. filler- fills
excessive space in capsule
2. glidant- allows materials
to be more free flowing and not stick to machines/mixers..etc
(2)
Question
#4a
In you own
words; explain
1. How Hard Gelatin
Capsules are orientated and filled.
Empty capsules enter an
orienting station(orienting blade and centrifugal force) from
the hopper and aligned correctly into respective slots. Caps are
then removed by vacuum suction. Powders are pushed into bodies by dosage
holes/plungers. Caps are then replaces back onto their bodies, and
eventually ejected by a set of upper and lower pings
(8)
2. List two (2) types of
filling methods used on Semi Automatic or Automatic machinery.
1.auger
2.piston/doser filling or vacuum filling
(2)
Question
#5
What colours
would you suggest for use in capsules containing the following?
1. Acetaminophen Caffeine
& Codeine (Narcotic).
White/orange
2. Flurazepam (tranquilizer).
blue/green
(2)
Question
#6
List the 5
stages in SUGAR COATING in order that they are applied
1. sealing
2. subcoating
3. grossing
4. addition of colour
5. polishing
6. Which of these steps
could be combined? (Circle them) steps 2,3,4
7.
How is the sugar coating applied-made in
conventional pans pouring liquid onto the product; or
sprayed on. (8)
Question
#7
List the
stages a drop of solution must go through to form a film during FILM
COATING.
1. ____formuation
of a drop________________________________________________________________
2. ____drop
contacts the solid surface_________________________________(impingement)_______________________________
3. ____drop
spreads________________________________________________________________
4. ____neighbouring
drops coalesce______________________________________________(wetting
and spreading)__________________
5. ________________________________________________________________________additional
drops form layers_____________________________________________
6. ________________________________________________________________________A
dry uniform film results after evaporation____(coalescence
adhesion&autohesion)_
7. How is film coating
applied to tablets____________________________________________droplets are
sprayed on, some penetrate core, and
some coalesce and build up a film on the core. A film is created when sufficient
solution is present._____________________
(8)
Question
#8
List four
uses of a fluid bed dryer (other than simple drying). What is the most
efficient way to use fluid bed equipment for granulating & drying?
1. .granulating and drying
2. .pellet coating
3. .pellet manufacturing
-spheronizing
4. .high shear granulating-
dense material
5.
.wurster coating
(4)
Question
#9
List 5
reasons for coating tablets.
1. .improve look
2. .mask odour
3. .increase ease of
swallowing
4. .easier to handle on high
speed packaging lines
5. .improved product stability
6.
.change drug release
properties (delayed/enteric release)
(5)
Question
#10
List 4
properties required in a tablet core to allow for a good coating to be applied
1. .it must not be too
soft/friable
2. .there should not be entrapped
air to prevent laminating or capping
3. .engraving cut should be
open enough or prepicked to allow coating
4. .it should have a correct
shape (caplet vs modified caplet)
(4)
Question
#11
What are
the 2 official methods for producing Water for Injection USP?
1. .distillation
2. .reverse osmosis
(2)
Question
#12
What 2
ingredients are required to be added during the production of Multi Dose Vials
containing Adrenaline? (Sensitive to Oxygen) Give the functional name and list
2 specific examples of each. -
1. ___ Anti-oxidants ---1.sodium
metabisulphite_________________ 2.tartaric
acid ____________________ __________________
2.
___perservatives_________________ ________1.benzyl alcohol__2.
parabenzoates__________ __________________
3.
sodium chloride+WFI = to balance ions (6)
Question
#13
How do we preserve
the Membrane in a Reverse Osmosis System and increase the amount of
water produced?
Sediment
filter and carbon filters first remove larger particles/chemicals
More pressure would be
used to force water through the membrane
Membrane is configure to
split feed water into 1.purified stream and 2. washed away stream that
carry away rejected contaminants.
(2)
Question
#14
How would
you prepare Simple Syrup for production of large quantities of cough
syrup?
Syrup
USP- sucrose is added to boiling water, stirred, filtered and
color is added. API are added when syrup cools to lower temperature
(3)
Question
#15
List 4
thickening agents used in the manufacture of Syrups and Suspensions.
1. .methyl cellulose
2. .carboxymethylcellulose
3. .guar gum
4.1.
4.
tragacanth
5.
xanthan, cellulose gums
(4)
List 4
Sweetening agents (Natural)
1. .liquid glucose
2. .maltose
3. .beet sugar
4. . natural sucrose/sugar (4)
Question
#17
List 3
Sweetening Agents (Synthetic)
1. .aspartame
2. .asulfame
potassium(nutrasweet)
3. .saccharine
(3)
Question
#18
List 4
popular flavoring agents with the appropriate colours to be used with them.
1. .chocolate mint-brown
2. .orange/ grapefruit- orange
3. .grape- purple
4. . strawberry/cherry - red
(4)
Question#19
Other than
using Synthetic sweeteners, is there another type of syrup that could be used
for Diabetics?
.
sorbitol syrups- poorly
absorbed from gut (2)
Question
#20
What part
do the following play in this Syrup of Acetaminophen? (Some have more than
one function)
Which ingredients
solubilize the active ingredient? (8)
|
ITEM # |
INGREDIENT |
PURPOSE
IN SOLUTION |
|
1 |
Acetaminophen |
API |
|
2 |
Alcohol
90% |
Soluabilizing
agent, preservative, sweetener |
|
3 |
Glycerin |
Solubilzer,
sweetener |
|
4 |
Propylene
Glycol |
Solubilzer,
sweetener |
|
5 |
Sucrose
Granular |
Preservative,
sweetener, thickening |
|
6 |
Liquid
Glucose |
Sweetener |
|
7 |
Parahydroxy
Benzoates |
Preservatives |
|
8 |
Acid
Orange G Colour |
Coloring |
|
9 |
Tutti
Frutti Essence |
Flavor |
|
10 |
Purified
Water to |
solubilizer |
Question
#21
Suggest a
method of manufacture the syrup above on a large scale – list some equipment to
manufacture a 1000L batch. Refer to table in question #20 for the ingredients
to be used in this syrup!
. STIRRING
WITH HEAT (Syrup USP)
-
.
1. add Sucrose and
preservatives to boiling water, then cool and
mix with dissolved actives
2. .stir with sylverson mixer
3. add all other ingredients
(colour,flavour,pH adjust)
4. filter using a filter press
5.
fill into bottles
3.1.
.
4.6.
.
5.7.
.
6.8.
.
7.9.
.
(10)
Question
#22
List four
(4) USP methods for Sterilization. List an item that could be sterilized with
the method
1. .Steam – injections, metal
tubes
2. .dry heat- empty glass
containers
3. .filtration- injections,
nasal/ophthalmic drops
4. .ionizing radiation-
disposable medical devices (eg. filters
5.
filling using aseptic
technique – (eg. blow
fill seal ampoules in ‘sterile’ environments) (8)
Question
#23
What are
the two main differences between a Syrup and a Suspension?
a)
(Syrup).concentrated colutions of sugar and contain
solvents that solubilize insoluble drugs
.
b)
(Suspension).particles are suspended in the solution. Particles
should settle slowly but readily disperse on gentle shaking of the container
.
(4)
Question
#24
What is the
filter size that must be used to produce a sterile solution?
.
0.22 Micron
What would
you do to prolong the use of this Sterile Filter?
.prefilter
solution in 0.45micron filter, filter solution in highly sterile environment,
use cross flow method instead of dead-end method
.
(2)
Question
#25
Complete
these tables by listing the use of the ingredient in these formulations
DIAZEPAM Tablets
|
INGREDIENTS |
PURPOSE IN FORMULATION |
|
Diazepam |
API |
|
Lactose |
Diluent/binder |
|
Cornstarch (3 uses) |
Diluent/lubricant/glidant |
|
Microcrystalline Cellulose |
Distegrant |
|
D&C Yellow #10 |
Color |
|
Sunset Aluminum Lake 40% |
Color |
|
Magnesium Stearate |
Lubricant |
CALCIUM TABLETS
|
INGREDIENTS |
PURPOSE IN FORMULATION |
|
Calcium Carbonate |
Ingredient for coating
(subcoating stage) |
|
Crosscarmellose Sodium |
Disintegrant |
|
Sodium Lauryl Sulfate |
Disintegrant |
|
Magnesium Stearate |
lubricant |
|
Hydroxypropyl Methyl
Cellulose |
Polymer for aq coating |
|
Poly Dextrose |
Increases polymer
permeability for coating |
|
Polyethylene Glycol |
Plasticizer for coating |
|
Titanium Dioxide |
Color (grossing stage in
coating) |
|
Brilliant Blue |
Color |
|
D&C Yellow # 10 |
Color |
|
Carnauba Wax |
Glossy finish/polish
coating |
(8)
Question #26
How would you produce this pink
oil in water cream? List the stages of manufacture, temperature, conditions
order of addition of ingredients.
1.
Stearic
Acid (Triple pressed) 0.760Kg
2.
White
Beeswax 13.590Kg
3.
Spermacetti 7.550Kg
4.
White
Petroleum Jelly
15.100Kg
5.
Mineral
Oil
56.850Kg
6.
Borax (Emulsifying Agent)
1.880Kg
7.
De-ionized
water
13.270Kg
8.
Rose
Oil Concentrate (Perfume) 0.010Kg
9.
Red
Dye #40 0.010Kg
1.
.melt 1-4 together in
jacketed kettle
2.
.heat to 65 Deg C
3.
.add 5
4.
.dissolve 6 in 7, heat to 65 Deg C
5.
add red dye #40 to water
phase
5.6. .slowly add oil phase to
water phase, and mix continuously
6.7. .cool to 25-30Deg C
7.8. .add perfume
8.9. . mix
(8)
Question
#27
A tablet
with the formula listed below has to be film coated (Aqueous Film).
At present,
the friability tends to be high after compression - especially in winter. What
precautions could be taken to ensure success of the final product. Without
changing any raw material?
INGREDIENT Per
Tab.
Acetylsalicylic Acid USP
(Crystals) 300
mg
Caffeine USP (Powder) 30 mg
Starch N.F. (9-13% moisture) 35mg
365
mg
1. .ensure correct speed of
drying to prevent sticking/picking
2. .control pan RPM, supply
air humidity, solution delivery rate
3. .prevent entrapped air in
tablet
4. .ensure correct(expanded)
core temperature before spraying
(4)
Suggest a formula for a CLEAR aqueous
film coating solution for this product. List the type and proper name of
the ingredients.
1. .polymer- HPMC ( and maybe
poly Dextrose to help permeability)
2. .plasticiser- polyethylene
glycol
3. .pigment- aluminum oxide
4. .water (8)
Question 29
Why is
Yellow Petroleum Jelly preferred in the manufacture of ophthalmic ointments? (2)
.white
always contain some residual sulfite from bleaching process
Question
30
List three
uses for transdermal patches. List BOTH the Medicinal use with the active
ingredient.
1.
.fentanyl- 72hr systemic delivery
of potent opiod analgesic
2.
.nicotine- continuous&systematic delivery of
nicotine as aid to cessation of smoking
3.
.Scopolamine- controled release of scopolamine for
continuously 72hrs. prevents nausea from motion sickness (6)
Question
31
Acetaminophen
Tablets 500mg.
These tablets were made in a fluid bed by spray granulation and fluid bed drying..
On compression the tablets started splitting and capping.
(Tablet Formula per tablet)
1. Acetaminophen 500mg
2. Hydroxy-propyl cellulose 5mg
3. Magnesium Stearate 2mg
4. Croscarmellose Sodium 2mg
1 is granulated with a mixture of 2 dissolved in sufficient water to allow a good spray for spray granulation. 3 & 4 are added to the mix after the granulation has been screened and dried.
What
could have caused this problem? List at
least 3 causes in granulating and 3 in compressing.
1.
granulation
2.
.too little liquid
2.3.
.over heating / drying
3.4.
.insufficient drying, too much liquid, too much
mixing
4.5.
.incorrect nozzle height
5.6.
.Compressing
6.7.
.excessive compression pressure
7.8.
.too rapid expansion on ejection
8.9.
.under weight/ thickness
10.
air entrapment in granules (6)
The formula from Question 31 is encapsulated - during encapsulation, the bottom of the capsules dented.
List three possible causes for
this.
1. .compression pressure too
high
2. .doser out of centre to
bodies
3. . too much wear in cap
bushings
(3)
Question
33
Metoprolol
Tablets compressed as a capsule shaped tablet with a full bisect are breaking
in the coating pan. Some cores are soft, others, comply with compression
specifications. Dissolution and all other tests are acceptable
Tablet
Formula Per
Tab Coating
Formula
Metoprolol USP 100mg Hydroxypropyl
methyl cellulose
Lactose NF
60mg Polyethylene
Glycol
Microcrystalline
cellulose 30mg Blue
Dye Lake #2
Cab-o-Sil 2mg Purified
Water
Croscarmellose
Sodium 2mg
Magnesium
Stearate
5mg
What could be causing this problem - list as many causes
that you can think of from compounding, granulation, compression and coating
1.
too little liquid in granulation
2.
layering or separation in hopper
3.
excess circulation causes too many fines
4.
pressure roll bearing or pivot worn
5.
inadequate circulation in compression stage
6.
air entrapment in granule from granulation stage
7.
humidity in compression area
8.
poor punch face conditions
9.
insufficient mixing time
10.
insufficient binder
11.
press running too fast
(10)
Question
#34
On coating,
the Blue coating fades in time. What could be the cause of this? (2)
1.
1.It has
different soluability characteristics.
2.
It might be light
sensitive
Name three (3) binders used to manufacture tablets. What is
it about the physical size or shape of the material that makes it an effective
binding agent?
1. .microstalline cellulose
ph102 – many empty places inside structure for material to enter
2. .dicalcium phosphate-
porous
3. .powdered cellulose-
stacked matrix of flakes allow material to get trapped inside (6)
Question #36
Name three (3) disintegrating agents used to manufacture
tablets. What is it about the physical size or shape of the material that makes
it an effective disintegrating agent?
1. .croscarmellose sodium-
worms like- brings water to center of tablet from exterior
2. .starch- porous and varying
size, allows water to enter tablet
3. . crospovidone-
porous and allows water to enter tablet (6)
Question #37
Using the guidelines of - “Ingredients required in a Mix” -
devise formulations for the following products. Each formulation must contain:
1. Active Ingredient
2. Binder (If required)
3. Filler (If required)
4. Glidant (0.5-1%) (If required)
5. Lubricant (0.5-1%) (If required)
6. Disintegrant. (If
required) (As per Raw material listing – 10% for Starch, 4-8% modified Starch,
0.5-2% Super Disintegrants)
You can make the product up to any weight required BUT
REMEMBER smaller is better. In each case, list your actives and inactives –
list the inactives by their property e.g. Glidant etc.
1. A tablet (to
disintegrate)
containing 500 mg of Acetaminophen, 30 mg of Caffeine and 8 mg of
Codeine
2. A tablet (to be
coated)
containing 300 mg of Ibuprofen – List some coating Ingredients.
3. A tablet (to chew
or dissolve)
containing 250 mg of Ascorbic Acid (Vitamin C)
Fill in your answers in the tables below. You do not have to use all the lines in the table to create a
tablet – IF YOU ONLY NEED 3 INGREDIENTS –
USE 3 LINES!
DISINTEGRATING TABLET
|
INGREDIENTS |
PURPOSE IN FORMULATION |
Estimated QUANTITY PER
TABLET |
|
ACETAMINOPHEN |
ACTIVE INGREDIENT |
500 mg |
|
Codeine |
Api |
8mg |
|
Caffeine |
Api |
30mg |
|
Magnesium stearate |
Lubricant |
7mg |
|
Crosscarmellose sodium |
Disintgrant |
7mg |
|
Starch |
Binder/filler |
100mg |
|
Cab-o-sil |
Glidant |
7mg |
|
|
|
|
|
|
|
TOTAL 650 – 900 mg |
(12)
TABLET TO BE COATED LIST SOME
COATING INGREDIENTS!
|
INGREDIENTS (Core) |
PURPOSE IN FORMULATION |
Estimated QUANTITY PER
TABLET |
|
IBUPROFEN |
ACTIVE INGREDIENT |
300 mg |
|
croscarmellose sodium |
Disintegrant |
4.5mg |
|
Magnesium stearate |
Lubricant |
4.5mg |
|
Cab-o-sil |
glidant |
4.5mg |
|
Starch |
Filler/binder |
140mg |
|
|
|
|
|
|
|
|
|
INGREDIENTS
(Coating) |
|
|
|
HPMC |
Polymer |
10mg |
|
Glycerine |
Plasticizer |
1mg |
|
Aluminum oxide |
dye |
5mg |
|
|
|
|
|
|
|
|
|
|
|
TOTAL 450-500 mg |
(12)
CHEWABLE TABLET
|
INGREDIENTS |
PURPOSE IN FORMULATION |
Estimated QUANTITY PER
TABLET |
|
ACSORBIC ACID |
ACTIVE INGREDIENT |
250 mg |
|
Guar gum |
Thickener/stabilizer |
50mg |
|
Aspartame |
Sweetener |
20mg |
|
Microcrystalline
cellulose |
Binder/ dispersing
agent |
25mg |
|
Magnesium stearate |
Lubricant |
5mg |
|
|
|
TOTAL 350 – 450 mg |
(12)
TOTAL
245
Grades:
A+ 90 % to 100%
A 80 %
to 89 %
B+ 75 % to 79 %
B 70 %
to 74 %
C+ 65 % to 69 %
C 60 %
to 64 %
D 55 %
to 59 %
F
0 % to 54 %