COMMERCIAL MANUF PART 1 Flashcards
1
Q
It deals with a subject both fascinating and vitally important for the pharmaceutical industry
A
Pharmaceutical process scale-up or commercial manufacturing
2
Q
It is generally defined as the process of increasing the batch size.
A
Scale-up
3
Q
It is the operation that brings about separation or isolation of a single chemical constituent or a group of
chemically related substance.
A
Separation
4
Q
It uses a single mechanical manipulation.
A
Simple process
5
Q
It is used to separate two immiscible liquids.
A
Separatory Funnel
6
Q
For two miscible liquids
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Distillation
7
Q
For two solids
A
Garbling
8
Q
Used to separate solid from liquid
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Centrifugation, filtration, expression
9
Q
Requires the formation of a second phase by the addition of a liquid, solid, or gas plus mechanical manipulation
A
Complex Process
10
Q
A separation process where an optically transparent liquid is obtained, which passes through a porous
substance (filter/filtering medium)
A
FILTRATION
11
Q
Nature of precipitate is known → larger particles are easier to filter than smaller particles
A
FILTRATION
12
Q
Have the tendency to occlude the pores of the bed, thus hinders passage of filtrate
A
Smaller particles
13
Q
Build up on the filter tends to form a non-porous, densely packed bed that resist passage of the
filtrate
A
Smaller particles
14
Q
It has channels that impart porosity (Porosity is defined as being full of tiny holes that water or air can
get through)
A
Filtering media
15
Q
ability of the filter medium to eliminate solid material form the liquid
A
Retention
16
Q
Speed at which the purified liquid/filtrate is recovered
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Filtration rate
17
Q
Speed of the flow of the liquid through the filter bed
-retarded by the viscosity of the liquid
A
Flow rate
18
Q
5 types of filtering media
A
- Filter paper
- Membrane Filters
- Cotton Fibers
- Glass wool filters
- Sintered Glass filters
19
Q
Types of filtering media that is FOLDED or FLUTED
A
Filter paper
20
Q
Type of filtering media that is similar to a cloth; pure or derived cellulose products with uniform micropore structure (10nm to 10um)
✓ used in chemical, microbiological, and bacterial analyses
A
Membrane filters
21
Q
Types of filtering media that is:
✓ Absorbent
✓ loosely inserted in the neck of the funnel
✓ disadvantage: refiltration is necessary
A
Cotton fibers
22
Q
Type of filtering media that is resistant to chemical action, thus, are used for highly reactive chemicals (ie: strong acids)
A
Glass wool filters
23
Q
Type of filtering media that is:
✓ flat or convex plate with Jena powdered glass that are molded together
✓ vacuum attachment required
✓ used to filter parenteral solutions
A
Sintered glass filters
24
Q
to avoid loss and/or explosion, cover the funnel and the receiving vessel.
A
Filtration of volatile liquids
25
- increases the efficiency of the filtration process
- must be soluble and inert
Adsorbents
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✓ not the palpable kind (impalpable: incapable of being felt by touch; so finely divided that no grains or grit can
be felt)
Purified Talc
27
✓ for general filtration processes
✓ inert
✓ adsorbs liquid
Kieselguhr or pure silica
28
✓ fuller’s earth or kaolin in hydrated form
✓ used to filter fixed oils but should not be used for liquid with coloring matter or alkaloidal principles
Siliceous earth or clay
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✓ adsorbs color, odor, alkaloids, and glycosides
Charcoal
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✓ readily react with acids and possess a finite solubility in water with a production of an alkaline aqueous solution
which can precipitate alkaloids
✓ not for general filtration processes
Chalk, magnesium carbonate
31
- aids in the filtration process; can use pump-acting process by water pressure where no leaks should be present
in the connections
- Ex. Buchner filter; Gooch crucible (perforated) and flask
Vacuum filtration
32
- the process by which finely divided solids and colloidal materials are separated from liquids without the use of
filters
CLARIFICATION
33
It is employed when the contaminating material is finely subdivided, amorphous, or colloidal in nature
CLARIFICATION
34
Tends to plug a filtration medium rapidly
CLARIFICATION
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✓ simplest method; least amount of labor and expense
✓ the sediment formed is a sludge which separates due to gravity from a liquid
✓ Ex. Fixed oils and vegetable oil
Gravitational sedimentation
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(ie: paper, talc albumin, gelatin, and polyamines)
✓ added, shaken and removed by filtration
✓ acts to reduce turbidity by physical adsorption
Use of a clarifying agent
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- a process of depriving solutions of color by use of an adsorptive medium
- Ex: Animal charcoal/bone black, wood charcoal, activated charcoal, bentonite, kaolin, fuller’s earth
DECOLORIZATION
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- simplest method for the separation of a solid from its soluble impurities
- involves washing and subsequent agitation of the solid with an appropriate solvent, allowing the solid to settle
then removing the supernatant liquid
DECANTATION
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repeated to attain the degree of desired purity of the solid
- conveniently done with a lipped vessel that is not filled to capacity
- stirring rod is used as a guide to steady the hand of the operator
DECANTATION
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- straining
- it separates the solid from the liquid by pouring the mixture on a cloth or porous material that will permit the
fluid to pass through but will retain the solid
COLATION
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it is filtration using larger pores in the straining medium/ cloth (flannel, muslin, wool, cheesecloth) which is
colorless and washed before use (soak in distilled water for a few hours, rinsed, boiled in distilled water then
rinsed well)
COLATION
42
Forcibly separating liquids from solids
EXPRESSION
43
Best method; uses a cloth
Spiral twist press
44
for large scale pressing of oily seeds, fatty substances; uses rubber
- care must be taken to apply the force gradually and not to use it on corrosive materials
Roller press
45
- expensive but most economical in terms of the increased power obtained with the least labor
the principle is based on the fact that pressure exerted upon an enclosed liquid is transmitted equally in all
directions
Hydrostatic or Hydraulic press
46
PRECIPITATION and CRYSTALLIZATION
Occurs in 3 steps:
1. Supersaturation
2. Formation of nuclei
3. Growth of crystals
47
It evaporate solvent → cool → formation of crystals
Supersaturation
48
thought to consist of 10 to a few hundred molecules having the spatial arrangement of
the crystals that will be grown ultimately from them
Formation of nuclei
49
suspension → Ostwald ripening (formation of hard cake)
Growth of crystals
50
careful temperature control and seeding with desired crystal form is necessary
existence of polymorphs
51
It depends highly on impurities in the solution, pH, rate of
stirring, rate of cooling, and the solvent.
the habit or shape of the crystal form
52
- putting together of ingredients in one mass or assemblage with more or less thorough dispersion of the
constituted elements among one another
MIXING
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- objective: to obtain dosage units which contains the same quantity of drug substance
MIXING
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✓Involves the movement of a relatively large portion of the fluid being mixed from one location in the
system to another
Bulk Transport
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✓Makes use of paddles, revolving blades or other mechanisms or shuffling which move adjacent
volumes of the fluid in three dimensional directions
Bulk transport
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✓Must result in a rearrangement or permutation of the various portions of the fluid being mixed to be
considered effective
Bulk transport
57
Direct result of turbulent fluid flow which is the random fluctuations of fluid velocity at any given point
within the system
Turbulent mixing (turbulent: moving in an irregular or violent way)
58
based on streamline or laminar flow
and encountered in processing highly viscous liquids, but also in stirring that is gentle and adjacent to
stationary surfaces in a vessel
Laminar mixing
59
achieved by mixers which stretches and sometimes even folds the fluid being mixed (the mixing
produces a folding effect as the layers of the fluid are stretched)
laminar mixing
60
Involves diffusion which results from thermal motion of the molecules (involves heat to cause vibration
of molecules)
Molecular diffusion
61
Usually performed with laminar mixing to reduce sharp discontinuities at the interfaces between the
fluid layers
Molecular diffusion
62
✓ used when material to be mixed is limited in volume and can be conveniently contained in a suitable
mixer
Batch mixing
63
✓ system consists of two primary components
(a) a tank or other container suitable to hold the material being mixed
(b) a means of supplying energy to the system so as to bring about reasonably rapid mixing
Batch mixing
64
✓ propellers produce radial flow; turbines produce axial and tangential flow
Impellers (propellers and turbines)
65
✓ propellers are most efficient when they can run at high speed in liquids of relatively low viscosity
Impellers (propellers and turbines)
66
Usually arranged in a way that allows the buoyancy of the bubbles to lift the liquid from the bottom to
the top of the mixing vessel
Air jets
67
Used in liquids of low viscosity, non-foaming, unreactive with the gas employed and non-volatile
Air jets
68
Fluids are pumped through nozzles arranged to permit good circulation of material throughout the
tank
Fluid jets
69
Generate turbulent flow in the direction of their axes (like propellers); does not generate tangential
flow
Fluid jets
70
✓ this produces an uninterrupted supply of freshly mixed material; desirable in handling very large
volumes of material
✓ accomplished through the use of:
a. a tube or pipe (through little back flow or recirculation)
b. in a chamber (in which a considerable amount of holdup and recirculation occur)
✓ the feed rate within the tube is carefully controlled and should be uniform via an exact metering
device
✓ if the rate is difficult to control, the tank type is used
✓ complex arrays of interconnected tanks (series or parallel) can be used for mixing
Continuous mixing
71
Factors to consider in mixer selection
a. Physical properties of the materials to be mixed (ie: density, viscosity, miscibility)
b. Economic considerations regarding processing (ie: time required for mixing, and the powder expenditure
necessary)
c. Cost of equipment and its maintenance
72
Selection of equipment depends on viscosity and density of the fluid to be mixed
Monophase Systems
73
▪ Best mixed by method that generate a high degree of turbulence and circulate the entire
mass of material
▪ Mixed air jets, fluid jets, and high-speed impellers
Low viscosity
74
▪ Mixed by turbines of flat blade design (relative insensitivity of their power consumption to
density or viscosity)
High viscosity
75
- Composed of several liquid or solid phases
- Involves the subdivision or deaggregation of one or more of the phases present with subsequent dispersal
throughout the mass of material to be mixed (may involve homogenization, suspension formation, and
emulsification)
Polyphase Systems
76
- Mixing requires the subdivision of one of the phases into globules which are successively reduced in
size and are then distributed throughout the bulk of the liquid
- Selection of equipment depends on viscosity of the fluid to be mixed
Immiscible liquids
77
▪ Requires high shear rates produced by passing the fluid under high pressure through small
orifices or by bringing it into contact with rapidly moving surfaces
Low viscosity (ie: emulsions)
78
▪ Dispersed by the shearing action of two surface in close proximity and moving at different
velocities with respect to each other
▪ Achieved in paddle mixers (in which the blades clear the container wall by small tolerance)
▪ Relatively efficient since they (1) generate sufficient shear to reduce globule size and (2)
induce sufficient circulation of material to ensure a uniform dispersion throughout the
completed mixture
High viscosity (ie: ointments)
79
▪ Mixing depends on separation of aggregates into primary particles and the distribution of these
particles throughout the fluid
Finely-divided solids in Liquids
80
▪ Mixing is done with the help of equipment like high speed turbines which generate shear forces of
sufficient intensity to disrupt aggregates
Finely-divided Solids in Liquids
81
efficient in deaggregation of solids but are typically inefficient in distributing
the articles uniformly through the entire mass
Muller mixers
82
composed of abrasion-resistant rollers arranged to come into close
proximity to each other which are rotated at different rates of speed (materials coming in between the rollers are crushed, depending on the gap, and are also sheared by the
difference in rates of movement of the two surfaces)
Roller mixers
83
▪ Consists of a container of one of several geometric forms which is mounted so that it can be
rotatedabout an axis
▪ The resulting tumbling motion is accentuated by means of baffles or simply by virtue of the shape of
the container
Tumbling mixers
84
a device used to restrain the flow of a fluid, gas, or loose material or to prevent the spreading of
soundor light in a particular direction
BAFFLE
85
Twin-shell blender
o Takes the form of a cylinder that has been cut in half approximately a 45-degree angle with its long
axis and then rejoined to form a “V” shape
o As the blender tumbles, the material randomly mixes which causes the final blend to be very
homogenous
86
Takes the form of a cylinder that has been cut in half approximately a 45-degree angle with its long
axis and then rejoined to form a “V” shape
Twin-shell blender
87
As the blender tumbles, the material randomly mixes which causes the final blend to be very homogenous
Twin shell blender
88
Consists of a stationary container to hold the material and moving crews, paddles or blades to bring
about mixing
Stationary mixers
89
Does not depend entirely on gravity; useful in mixing solids that have been wetted (sticky or plasticstate)
Stationary mixers
90
consists of a horizontal cylindric tank usually opening at the top and fitted with helical blades
• Blades are mounted on a shaft through the long axis of the tank and are often of both right -
and-left-hand twist
Ribbon blender
91
powders are lifted by a centrally located vertical screw and allowed to cascade to the bottom of the tank
Helical flight mixer
92
- mechanical process of reducing the particle size of solids
MILLING
93
aka: comminution, crushing, disintegration, dispersion, grinding and pulverization
MILLING
94
Reasons in MILLING
a. reduce bulk volume
b. improve solubility
c. aid in processing
95
Factors Affecting Size Reduction
1. Energy
2. Rate of feed
96
size reduction begins with the opening of any small cracks that were initially present
Energy
97
in general, fine grinding requires more energy (because of the increased new surface and more energyis needed
to initiate cracks)
Energy
98
slow: less reduction in particle size (material is discharged readily)
fast: greater reduction of particle size (material stays longer in the milling chamber)
Rate of feed
99
Classifications of Milling Equipment
- based on size measured in mesh (number of openings per linear inch of a screen)
1. coarse (larger than 20 mesh)
2. intermediate (200 to 20 mesh; 74 to 840 microns)
3. fine (smaller than 200 mesh)
100
Basic Parts of a Milling Equipment
1. feed chute (delivers the material)
2. grinding mechanism (consists of a rotor and a stator)
3. discharge chute
101
Three basic actions involved in comminution:
1. attrition
2. rolling
3. impact
102
breaking down of materials by rubbing action between two surfaces
attrition
103
use of heavy rolling member to crush and pulverize the materials
rolling
104
involves the operation of hammers (or bars) at high speeds; these strike the lumps of materials and throwthem
against each other or against the walls of the containing chamber
impact
105
✓ The choice depends on the use of the product and its subsequent processing.
Wet and Dry Milling
106
- recommended in products which undergo chemical or physical change in water
- limit of fineness in reached in the region of 100 microns when the material cakes on the milling chamber
- may use grinding aids to facilitate size reduction
- ie: ammonium salts, aluminum stearate, arylalkyl sulfonic acid, calcium stearate, oleic acid
andtriethanolamine salts
Dry Milling
107
- beneficial in further reducing particle size but flocculation restricts the lower limit to approximately 10 microns
- eliminates dust hazards and is usually done in low speed mills (which consume less energy)
- may use dispersing agents to increase milling efficiency
- ie: silicates and phosphates
Wet milling
108
- removal of liquid from a material (usually by the application of heat)
- accomplished by the transfer of a liquid from a surface to an unsaturated vapor phase
DRYING
109
systems in which there is no relative
movement among the solid particles
being dried, although there may be
bulk motion of the entire drying mass
Static Bed Dryer
110
only a fraction of the total number of
particles is directly exposed to heat
sources
Static Bed Dryer
111
exposed surface can be increased by
decreasing the thickness of the bed
and allowing drying air toflow
through
Static Bed Dryer
112
• systems that allow drying of materials through movements of plates, trays and conveyors
Moving Bed Dryer
113
• systems that allow the dried solid material to become partially suspended in gas streams
• gas is allowed to flow upward through a bed of particulate solids at a velocity greater than the settling
velocity of the particles and less than the velocity for pneumatic dryers
Fluidized Bed dryers
114
• also known as compressed air dyer
• systems that remove water vapor from compressed air
• may be used in drying fluid materials such as solutions, slurries, and thin pastes
Pneumatic Dyers
115
- powder particles adhere to one another to form agglomerates
- operation which increases the density and uniformity of the mixture for the compression process
- pharmaceutical process that attempts to convert materials into aggregates called granules which possess
improved flow characteristics
GRANULATION
116
Reasons for granulation:
a) to impart good flow properties to the material
b) to increase the apparent density of the powders
c) to change the particle size distribution
d) uniform dispersion of active ingredient
117
METHODS OF GRANULATION
1. Wet Granulation
2. Dry Granulation
118
- oldest and most common granulation technique
- process involves blending at high and low/or low forces with the addition of a liquid
Wet Granulation
119
✓ promote size enlargement to produce granules and thus improve the flowability of the blend during the
manufacturing process
Binders
120
Examples:
a) Natural polymers: starch, pregelatinized starch
b) Synthetic polymers: PVP, Methycellulose, HPMC
these are called
Binders
121
-an atomized liquid is sprayed from the top or bottom directly onto the solids under a continuous air
stream with little or no shear
Fluid-bed Granulation
122
-a liquid containing dissolved or suspended solids is atomized and rapidly dried using a controlled air
stream to produce a dry powder which is agglomerated by forcing it again intothe atomizing zone
Spray-dry Granulation
123
-a liquid containing dissolved or suspended solids is atomized and rapidly dried using a controlled air
stream to produce a dry powder which is agglomerated by forcing it again intothe atomizing zone
Spray-dry Granulation
124
may be applied in continuous granulation process and is suitable for active pharmaceutical ingredientsthat are moisture and/or temperature
Dry Granulation (also known as the Fusion Method)
125
Dry Granulation also known as the?
Fusion Method
126
Small-scale production system used to test and validate a production technology before commercialization
PILOT PLANT
127
Filtration technique exemplified by Buchner Filter
Vacuum Filtration
128
Clarification technique employed for fixed oils and vegetable oils
GRAVITATIONAL SEDIMENTATION
129
A separation technique employed to segregate two solids
Garbling
130
Filter used in chemical and bacterial analysis
MEMBRANE FILTERS
