Module 3 Flashcards
________ is an essential element of many pharmaceutical processes. The ability to propel fluids through pipes and to direct materials from one
location to another is central to the successful manufacture of many products.
Fluid flow
_________ are a form of matter that cannot achieve equilibrium under an applied shear
stress but deform continuously, or flow, as long as the shear stress is applied.
Fluids
___________ is a property that characterizes the flow behavior of a fluid, reflecting the
resistance to the development of velocity gradients within the fluid.
Viscosity
Fluids having constant viscosity
and a zero shear rate at zero shear
stress
Newtonian Fluid
Fluids having variable viscosity,
and a variable relationship with
shear stress
Non-Newtonian Fluid
Deformation is not only a shear-induced phenomenon. If the stress is applied
normally and uniformly over all boundaries, then fluids, like solids, decrease in volume. This decrease in volume yields a proportionate increase in density.
COMPRESSIBILITY
______________ a property confined to a free surface and therefore not applicable to
gases, is derived from unbalanced intermolecular forces near the surface of a liquid.
This may be expressed as the work necessary to increase the surface by unit area.
Although not normally important, it can become so if the free surface is present
in a passage of small-diameter orifice or tube.
SURFACE TENSION
FLUIDS AT REST: HYDROSTATICS. For a fluid at rest, the force balance yields to:
Hydrostatic Equation
FLUIDS IN MOTION: At points along a horizontal streamline, higher pressure regions have lower fluid
speed and lower pressure regions have higher fluid speed.
The Bernoulli Equation
Used for measurements and flow
type determinations
The Reynolds Number
Reynolds for laminar flow
< 2000
Reynolds for turbulent flow
> 4000
Flow meters used for flow measurements in pipes containing steam. Used for flow testing purposes in production lines.
Orifice meter
Flow meters used in on-line installations. Used for flow measurement of gases.
Venturi meter
Flow meters used for flow measurements for a single point only.
Pitot tube
Flow meters used in bulk drugs and chemical industries. Used in fermentation systems for air control.
Rotameter
Valves used for isolation.
Gate Valve
Ball Valve
Diaphragm Valve
Valves used for control.
Globe Valve
Ball Valve
Butterfly Valve
Valves used for prevention of flow reversal.
Check Valve
Valves used for flow diversion.
Ball Valve
Plug Valve
Angle Valve
Pumps where energy is continuously applied to increase the fluid velocities
within the system.
Dynamic pumps
Pumps where energy is periodically applied unlike the dynamic pumps
Positive displacement pumps
Effective viscosity range of centrifugal versus positive displacement pumps
C: Efficiency decreases with increasing viscosity (max 200 cP)
PD: Efficiency increases with increasing viscosity
Pressure tolerance of centrifugal versus positive displacement pumps
C: Flow varies with changing pressure while efficiency decreases at both higher and lower pressures
PD: Flow insensitive to changing pressure but efficiency increases with increasing pressure
Priming of centrifugal versus positive displacement pumps
C: Required
PD: Not required
Flow at constant pressure of centrifugal versus positive displacement pumps
C: Constant
PD: Pulsing
Shearing (separation of emulsions, slurries, biologican fluids, food stuff) of centrifugal versus positive displacement pumps
C: High speed motor damages shear-sensitive mediums
PD: Low internal velocity ideal for pumping shear sensitive fluids
Pumps used for injection of polymerization inhibitors and in high pressure systems
Reciprocating pumps
Reciprocating pumps used in peristaltic and HPLC pumps and for spray systems in sugar coating and film coating operations
Piston pump
Reciprocating pumps used in transporting liquid containing solids, while hazardous, toxic, and corrosive liquids can also be handled
Diaphragm pump
Reciprocating pumps used for handling liquids at high pressure, used for transport viscous liquid and liquid contain suspended liquids
Plunger pump
Most used pump in the industry due to it being a low maintenance and high
efficiency pump
Rotary pumps
Rotary pump used for handling viscous or heavy liquid like vegetable oil, animal oil, waxes, used in aqueous film coating
Gear pump
Rotary (centrifugal) pump used for viscous liquid
Volute pump
Rotary (centrifugal) pump used for non-viscous and non-corrosive liquids
Turbine pump
Rotary (centrifugal) pump used for handling organic solvents
Deep well pump
Pumps used for pumping emulsions and creams, parenteral, in blood pumps for operations
Peristaltic pumps
Transfer of heat by means of molecular
excitement within a material without bulk motion of the matter.
Conduction
Law of conduction
Fourier’s law
The transfer of heat between two bodies by currents of moving gas or fluid.
Convection
Convection where Fluid flow is induced by an external force
Forced or Assisted Convection
Convection where Flow is caused by density differences cause by
temperature variations
Natural Convection
Heat transfer process by which the thermal energy is exchanged between two surfaces obeying the laws of electromagnetics
Radiation
Law of radiation
Stefan-Boltzmann law
Value of Stefan-Boltzmann constant
5.6073x10^-8 watt/m^2/K^4
_________ is conceptually and mathematically analogous to heat transfer. In most cases, unit operations and processes are diffusion limited.
MASS TRANSFER
Describes the movement of molecules from a higher concentration to a lower
concentration
Fick’s Law of Diffusion
FILTRATION
The process of separation of solids from a fluid by passing through a porous medium that retain the solids but allows the fluid to pass through. The liquid which has passed through the filter is called the filtrate.
The suspension of solid and liquid is
known as the _____.
slurry
The porous medium is known as the ______.
filter medium
The accumulation of solids on the filter is referred to as the _________.
filter cake
Factors affecting filtration:
- Fluid properties (density, viscosity, corrosiveness)
- Solid properties (particle shape, particle size, particle distribution,
compressibility) - Proportion of solids in the slurry
- Filtration objectives (do we collect the solid, liquid, or both?)
- Is washing necessary for the solids?
Flow of fluids through porous media which states that the rate of movement of water through porous media is
proportional to the hydraulic gradient.
Darcy’s law
The permeability coefficient, k, is a factor of the _________ and its _________.
bed porosity; specific surface area
___________ employing thick, granular beds are widely used in municipal water
filtration.
Gravity filters
Gravity filters operate at low pressures, usually less than _______, which gives low
rates of filtration unless very large areas are used. Their use in pharmaceuticals is very limited.
1.03x104 N/m2
_____ operate at higher pressure
differentials than gravity filters.
Vacuum filters
The vacuum filter pressure is limited naturally to about
________, which confines their use to the
deposition of fairly thin cakes of freely filtering materials.
8.27x104 N/m2
Despite this limitation, the principle of vacuum filters has been
successfully applied to _______ and
___________ cake filtration.
continuous; completely automatic
_____________ filters and _________ filters are most extensively used in the industry.
Rotary vacuum; leaf
_______ filters are used for slurries
requiring high pressure differentials
(i.e. low cake permeability). They may also be used when the
scale of the operation does not justify
the installation of continuous rotary
filters.
Pressure
In the ________, a material is placed in a rotating perforated basket,
which is lined by a filter cloth. This is used to separate a solid, which is retained at the cloth, from a liquid.
Centrifugal Filters
Centrifugal filtration is essentially a filtration process in which the ______ is of centrifugal origin.
driving force
The process is widely used for the separation of crystals and granular products from other liquors, but it is less effective if the slurry contains a high proportion of particles less than _____. The advantages of the process are _______.
1x10-4 m; effective washing and drying
The rate of the particle sedimentation is proportional to __________
particle size
The rate of sedimentation is proportional to the difference in the ________
density
Sedimentation rate is _____ when particle density is the same as the medium
zero
Sedimentation rate decreases as ___________ decreases
viscosity
The sedimentation rate increases as ___________ increases
gravitational force
Used for blood plasma separation, preparation of bacterial enzyme, manufacturing of insulin, clarification of olive and fish liver oil.
Sedimentation centrifuge
Centrifuge used for obtaining anhydrous product.
Filtration centrifuge
Centrifuge used in colloidal research for separate solid from liquid, with 85000 rpm.
Ultracentrifuge
Centrifuge used in colloidal research for separate solid from liquid, with 45 to 50 angle.
Angle centrifuge
Centrifuge used in colloidal research for separate solid from liquid, with 10000 rpm.
High speed centrifuge
Centrifuge used for separating crystalline drug like aspiring via filtration.
Perforated basket type
Centrifuge used when deposited solids offer high resistance to flow through sedimentation.
Non-perforated basket type
Semi-continuous type centrifuge through filtration.
Short cycle automated batch centrifuge
Centrifuge used for slurries contains 0.5 to 50% solids through sedimentation.
Horizontal centrifuge
Centrifuge used for separating liquid phase of emulsion through sedimenattion.
Super centrifuge
Centrifuge used in manufacture of antibiotics, separation of cream from milk, concentration of rubber wax removing solids from oils, inks through sedimentation.
De Laval Clarifier
Size Reduction in the Industry: Fine particles can be produced directly by controlled _______, in many cases the material is powdered in some kind of mill.
precipitation, crystallization,
or drying a fine spray of solution
Objectives of size reduction:
- Increases surface area to improve therapeutic efficacy
- Facilitates mixing and drying
- Allows particle size control
Factors affecting size reduction:
- Hardness
- Toughness
- Stickiness
- Moisture content
Common equipment for cutting
Cutter mill (100 - 80000 micron)
Common equipment for compression
Roller mill (50 - 10000 micron)
Comment equipment for impact
Hammer mill (50 - 8000 micron)
Common equipment for attrition
Colloid mill, roller mill (1 - 50 micron)
Comment equipment for impact and attrition
Ball mill, fluid energy mill (1 - 2000 micron)
Products produced from cutter mill
0.5 to 0.01 cm of fibrous, tough and soft material
Products that cannot be produced from cutter mill
Friable material
Products produced from roller mill
0.5 to 0.01 cm of soft material, cracking seeds before extraction
Products that cannot be produced from roller mill
Abrasive material
Products produced from hammer mill
0.5 to 0.01 cm for all types of material
Products that cannot be produced from hammer mill
Abrasive material
Products produced from fluid energy (jet mill) or microionized mill
1 - 30 micron for hard, friable, and therm labile substances like vitamin, antibiotics, enzyme, hormone
Products that cannot be produced from (jet mill) or microionized mill
Soft, sticky material
Products produced from ball mill
0.01 cm of soft, fibrous material and serial grinding
Products that cannot be produced from ball mill
Hard and abrasive
Products produced from end and edge runner mill
0.5 to 0.01 cm of fibrous, tough, sticky material
Products that cannot be produced from end and edge runner mill
Hard and abrasive
Powder standards
Coarse (sieve 10, 44%)
Moderately coarse (sieve 22, 60%)
Moderately fine (sieve 44, 85%)
Fine (sieve 85, 120%)
Very fine (sieve 120)
Microfine (350, 90% pass)
Superfine (90% pass thorugh a 10 micron)
Defined as an operation “in which two or more ingredients in separate or roughly mixed condition are treated so that each particle of any one ingredient is as nearly as possible adjacent to a particle of each of the other ingredients.
Mixing
Mixing objectives:
- to secure uniformity of composition, so that small samples withdrawn from a
bulk material represent the overall composition of the mixture, and - to promote physical or chemical reactions, such as dissolution, in which
natural diffusion is supplemented by agitation.
Systems that, given time, would spontaneously and
completely mix
Positive mixing
Any system in which phases will separate unless continuously agitated
Negative mixing
System where neither mixing or demixing will occur unless
acted upon by a system of forces
Neutral mixing
The transfer of groups of adjacent particles from one
location in the mass to another.
Convective mixing
The distribution of particles over a freshly developing surface.
Diffusive mixing
The setting up of slip planes within the mass.
Shear mixing
Used for low viscous liquid and rotate at <8000 rpm, not used for glycerin, liquid paraffin, castor oil. Various offset, angled, push-pull, baffled type propeller is use for liquid mixing.
Propeller mixer
It contains impeller and is used for viscous liquid like liquid glucose and due to high shear force use in emulsification and not for suspension. Various flat and curved blade, pitched vane and tilted type turbine is for mixing.
Turbine mixer
Agitator used for mixing and rotate at 100 rpm.
Paddle mixer
It is convective mixing, used for blending free flow material of uniform size and density.
Ribbon blender mixer (dry mixer)
It is shear and diffusion mixing. Rotation speed is 30-100 rpm. Various twin V-shape, double cone, cubicle, Y-shaped and cylindrical type tumbler is used for mixing.
Tumbling mixer
There are also mixers for semi-solid systems. ________ are also considered mixers.
Homogenizers
_______ are terms used to describe the extraction of soluble constituents from a solid or semisolid by means of suitable solvents.
Leaching or solid-liquid extraction
_________ is used to obtain therapeutically desirable portion and eliminate inert
materials by treatment with a selective solvent known as the menstruum.
Extraction
Solid ingredients are placed in a
stoppered container with the whole of
solvent and allowed to stand for a
certain period of time (with frequent
agitation) until soluble matter is
dissolved.
Maceration
The process in which a comminuted drug is extracted of its soluble constituents by the slow passage of suitable solvent through a column of a drug.
Percolation
_________ are dilute solutions containing the readily soluble constituents of the
crude drugs
Infusions
_______________ may be prepared by macerating the drug for a shorter period of time
Fresh infusions
Factors affecting choice of extraction process
Characteristic of the drug
Therapeutic value of the drug
Stability of the drug
Cost of the drug
Solvent choice
Concentration of the product
Recovery of the solvent from the marc
__________ is a process in which a liquid mixture is separated into its component
parts by vaporization. The vapor evolved from a boiling liquid mixture is normally
richer in the more volatile components than the liquid with which it is in
equilibrium.
Distillation
Factors affecting distillation method choice
Miscibility of the mixtures
Formation of azeotropes
Volatility of the mixtures (solvents and impurities)
Aqueous vs organic nature of the mixture
Removal of liquid from a solution by boiling the liquor in suitable vessel and
withdrawing vapor, leaving concentrate liquid residue.
Evaporation
Evaporation in the pharmaceutical industry is primarily associated with the
removal by boiling of water and other solvents in batch processes. However,
the principles that govern such processes apply more generally and are
derived from
a study of the transfer of heat to the boiling liquid, the relevant
physical properties of the liquid, and the thermal stability of its components.
Factors affecting evaporation
- Surface area of the liquid
- Temperature
- Agitation
Evaporator that contains liner as pan and use for aqueous and thermostable liquor through natural circulation.
Evaporating pan
Evaporator used for thermo labile materials through natural circulation.
Vacuum pan; evaporating stills
Evaporator used in sugar industry, concentrate cascara extract and not for foamy liquid through natural circulation.
Vertical tube evaporator (CALENDRIA)
Evaporator used for liquor that do not crystallize and not form scale and non-viscous through natural circulation.
Horizntal tube evaporator
Evaporator used for sugar, salts, and heavy chemical through natural circulation.
Vertical tube (basket type) evaporator
Evaporator used for insulin, vitamin, blood plasma, liver extract like thermolabile material and for foamy, corrosive liquid through natural circulation. Not for viscous liquids.
Climbing film (Kestner Tube) evaporator
Evaporator used for viscous liquid and when high percentage of evaporation is required through natural circulation.
Falling film evaporator
It’s a modified falling film evaporator used for highly viscous liquid through natural circulation.
Wiped/Rotary film evaporator (also LUWA)
As a unit operation, the term crystallization describes the production of a ________.
solid, single component, crystalline phase from a multicomponent fluid phase
In general, _________ is the most important underlying property of a solid
dictating many of its physicochemical properties including stability.
crystallinity
In the pharmaceutical industry, crystallization is usually performed on a small scale from solutions, often in jacketed or agitated vessels. The conditions of _________, , are usually established by experiment.
crystallization, necessary for suitable purity, yield, and crystal form
Nucleation and growth where particles mediated nucleation mechanism in amorphous Bi to nanocrystal transformation.
non-classical
Nucleation and growth where atoms or ions attached as a mechanism.
Classical
CRYSTALLIZATION EQUIPMENT
A. Cooling crystallizer
B. Evaporative crystallizer
C. Batch vacuum crystallizer
The vaporization and removal of water or other liquid from a solution,
suspension, or other solid-liquid mixture to form a dry solid.
Drying
Drying may be carried out to:
- improve handling characteristics, as in bulk powder filling and other
operations involving powder flow and - stabilize moisture sensitive materials, such as aspirin and ascorbic acid.
Convection dryer used for drying of chemical, powder, crude drugs, equipment, tablet granules not used for continuous processes.
Tray dryer (shelf dryer)
Convection dryer used for a short drying time (30 minutes), drying of tablet granules, plastic material, coal, inorganic salt, in fertilizer. It produces explosion and attrition and only for batch process.
Fluidized bed dryer (FBD)
Convection dryer used for drying of powder and granular solid not used for batch processes.
Rotary dryer (modified tunnel)
Convection dryer used for drying of paraffin wax, gelation, and soap not for batch processes.
Tunnel dryer (belt or conveyor dryer)
Conduction dryer for solids (granules)
Tray dryer (batch process)
FBD (batch process)
Tunnel/belt/conveyor dryer (continuous process)
Rotary dryer (continuous process)
Turbo dryer (continuous process)
Freeze dryer (batch process)
Pneumatic dryer (continuous process)
Vacuum dryer (batch process)
Conduction dryer for solution
Rotary dryer
Tunnel dryer
Pan dryer
Spray dryer
Drum dryer
Conduction dryer for paste or sludges
Vacuum dryer
Agitator dryer
Formulation and Pre-formulation Development
- Initial stages of the drug R&D
- Evaluation of uniformity and stability of formulations
- Dosage form development
Blending of Pharmaceutical Ingredients
- Excipient blending prior to dosage form
- API blending
- Uniformity of the drug ingredients
- Control of final blend (PSD, particle shape, moisture content, etc.)
Granulation
- In the simplest sense, granulation is the opposite of milling.
- Process by which small particles are bound together to form larger
particles, called granules. - Used to improve flow characteristics of powders and improve
compactability for tablet formation.
