In pharmaceutical technology, in order to achieve a well-defined technological purpose, heat is frequently transferred to some material to change its temperature, state of matter, or any other physical-, chemical-, biological estate.
Most common compounding processes which also require the operation of heating:
dissolving,
melting,
evaporation,
distillation,
extraction,
drying,
lyophilization,
sterilization.
Temperature (T) is a non-additive physical property of materials. Quantity of heat (Q) is the quantity of energy absorbed or lost after thermal interaction. The amount of heat invested into heating a body, is in linear proportion with the mass of material (m) and the specific heat capacity (C) and the difference of temperatures (ΔT):
t mC
Q = ∆ (1.)
Specific capacity of heat defines how much heat has to be transferred to a body with unified mass in order to increase its temperature with one Celsius degree.
Heating can be performed directly or in an indirect way.
Most commonly, direct heating is done with flame or other heat source (e.g.
immersion heaters), which means a heat transfer without any transfer medium. The most major disadvantage of this kind of heating is risk of overheating.
Indirectheating is slower, but allows a more even, consistent warming up. In this case, several transfer medium is used such as: air bath, liquid bath, sand bath. Air bath can be produced with hot air, liquid bath with heated water or oil depending on the temperature which should be achieved. Sand bath warms up much more slowly than the latter ones, but can provide temperature from room temperature to 200 Celsius degree deep in sand.
Mixing of the medium, which should be heated, assists the more even and consistent heat transfer in both cases.
At heat transfer, depending on material properties, and magnitude of transferred heat several phenomena can occur:
phase transition,
polymorphism,
pyrolysis.
Heat can be transferred by:
conduction
convection
radiation.
Conduction occurs in every case, if two bodies with different temperature contact with each other, or if temperature difference occurs between certain parts of the body.
Heat transfer happens in molecular size, in which the particles connecting to each other give the energy to each other. During this process, the higher temperature molecules with higher kinetic energy give a part of their energy to the nearby molecules having less energy. Due to this, temperature of the particles having less energy is risen, thus the heat has been conducted. In solid medium this is the only way of heat transfer, though in fluid or in gas state of matter may also occur. During the process, heat is transferred due to movement of electrons, longitudinal vibration and crashing of molecules with different speed depending on state of matter. The conduction becomes equilibrium or steady state, if the temperature in all part of the body remains invariable (stationary conduction).
Fig. 7.1.
Most major determining parameters of conduction Fourier’s basic formula for conduction:
L T A∆ λ
ϕ = (2.)
φ
heat transferλ
conduction factorA
surfaceL
thicknessΔ T
temperature differenceConvective heat transfer (convection) means a heat transfer with transportation
Chapter 7: Heat transfer
According to the Newton’s cooling law, the specific formula for convective heat transfer:
T A∆ α
ϕ = (3.)
α
convection factorOn the 2. Fig. it can be seen, that in practice the main types of heat transfers can be appeared simultaneously, thus may be mixed. The heat energy (Bunsen burner, electric hot plate) comes with conduction through the wall of flask, which induces an internal movement (convection) in the medium, which should be heated (Fig. 2.).
Fig. 7.2.
Convective heat transfer
In contrast with the previously mentioned heat transfers, the one developed by radiation can be prescinded from material, since it is a possibility of heat transfer without any transfer medium. Radiation spread with electromagnetic waves, which means that the radiation of warmer body is absorbed in the colder body.
The process of radiation can be specified by the Stefan-Boltzman formula:
AT4
εσ
ϕ= (4.)
ε emission capability
σ radiation constant of body T absolute temperature
Two wavelength ranges of electromagnetic wave are used during compounding:
infrared rays (10-12 -10-14 Hz), and
microwaves(10-8 -10-12 Hz).
The infrared rays are inter alia used to heat, melt, dry, while the microwaves are principally used for dielectric heating.
At the application of infrared ray, penetrating rays and energy input warm up the material. Its advantage, that there is no need of intermediate transfer medium, therefore the material does not contact directly with heat source.
Fig. 7.3.
Melting of ointment basis by infra lamp
During heating with microwaves internal heating develops, thus the heat absorption is more even and consistent, and the process heat of transfer lasts much shorter. This method of heat transfer is considerable in many view of pharmaceutical applicability, thereby the energy of microwaves is not usually sufficient to degrade bonds of the molecules, but in certain circumstances it is able to modify biological structures (damaging in bonds of molecules, cell membrane).
The temperature increase of heated material depends on:
time of heating,
composition,
dielectric properties of components,
water and salt content of composition.
The disadvantage of process of heating with microwaves is the possibility of
“selective heating” because of the dielectric properties of the different ingredients in the composition. The variant absorption capability of microwave, thus the different temperature within the material leads to difference in heating, so called “selective heating”.
The heat transfer can be carried out:
1) directly (e.g. cooling water with ice, warming it with addition of warm water) by contact of materials
2) indirectly (e.g. through wall of a tube) by without any contact of
Chapter 7: Heat transfer
The heat exchanger provides careful, even and indirect heat transfer with avoiding local overheating, in addition to the possibility to supply cooling too. These are essentially the devices and equipment, in which the two medium flowing in different area is separated by a wall, therefore they will not mix with each other. The heat transfer occurs on the surface of the separating wall.
Absorbed and lost quantity of heat equal in the heat exchanger, therefore:
2 2 2 1 1
1C T m C T
m ∆ = ∆ (5.)
from which the proportion of temperature differences:
1 1
2 2 2 1
C m
C m T T =
∆
∆ (6.)
The heat exchanger can be warmed up by hot water or steam through its cape, and can also be suitable for cooling by the flow of cold water. Heat transferred to the wall in unit time is a proportion with contact surface through the medium (heating medium) with higher temperature and with the thickness of the created layer around the wall and with the conduction factor.
In continuous mode the flow speed of liquid has to be regulated to obtain enough time for heat transfer. The affected media are separated by a solid wall.
The heat exchanger devices can be grouped into three main groups:
1) plate heat exchanger 2) cape heat exchanger and 3) tube bundle heat exchanger.
Plate heat exchanger consists of series of internal, pressed patterned heat transferring plates, which are restricted between plates closed by external plates. This type of exchanger are used to heat and cool liquids. The waviness of plates allows the turbulence of liquids, thus the better heat transfer developed through the wall of plates.
The heating and the medium which should be heated, flow in opposite direction in constrained path in two separated flow area and on different side.
Fig. 7.4.
Structure of plate heat exchanger
The cape heat exchangers are essentially two-layered equipments (duplicators), which are considered containers, surrounded by the external covering plate, namely the cape area. In the duplicators a determined amount of material is generally processed in the same time. Heat transfer is provided by transmission of warmed water, steam or oil or perfusion, depends on desired temperature. Mixing of the media assists the heat transfer between the wall of container and medium, and the heat convection inside the fluid.
In laboratories in pharmaceutical practice, duplicators with double walls and made of glass are used for heating materials, careful tempering. Connected with perfusion thermostat, liquid is warmed to appropriate temperature, or kept in constant temperature. Heat transfer can be helped by mixing.
Chapter 7: Heat transfer
Fig. 7.5.
Glass laboratory duplicator
The cape heat exchanger depending on task and usage with or without mixer, are suitable to perform chemical, namely exothermic and endothermic processes including dissolution, melting, evaporation, crystallization, fermentation, or other operations in a closed structure. The control of processes can be carried out with several integrated sensor (e.g. pH, temperature), or with periodic sampling. There is a possibility of control via computer.
Industrial duplicators with upper and lower driven mixer can be distinguished based on the modes of mixing.
Fig. 7.6.
Jacketed heat exchanger
Contrary to duplicators, tube bundle heat exchangers are continuous operating and dynamic devices. The flow speed between the continuously flowing media (fluids) determines the time of stay in devices, during which develops the heat transfer. This type of heat exchangers are devices consisted of parallel assembled tubes, in which the heat transfer is provided by mantle of tubes. Heat exchangers can be vertical or horizontal type.
The tube bundle wall closes the space between tubes. Chamber at the end of bundle can be influent or effluent, and turning (recirculating) chamber according to its function.
The flow of heat develops invariably due to the temperature difference, therefore is a precondition of heat transfer. The process of heat transfer lasts only until the temperature difference is persistent.
According to the flow direction of heat transferring medium and the medium, which should be heated, the heat transfer can be:
direct flow,
counterflow
cross-flow.
In case of direct flow tube bundle heat exchanger, heating medium, medium which should be heated flow in the same direction on the two side of separating wall.
Upon entry, the heated medium meets with high temperature heating medium, thus the temperature difference is initially high and then more and more decreases. The effluent temperature of heated medium cannot reach the effluent temperature of heating (cooling) medium.
Fig. 7.7.
Inflexible tube bundle heat exchanger with direct flow
In case of counterflow tube bundle heat exchanger, the input and output points of materials participating in heat transfer are not on the same side. At influent, the heated medium meet with a medium with low temperature (but warmer than the heated), which allows a slower and more careful heating. While the two media flows in an opposite direction, hence the heated medium meets with warmer and warmer heating medium and consequently end-temperature of heated medium can be higher than temperature of heating medium.
Chapter 7: Heat transfer
Fig. 7.8.
Inflexible tube bundle heat exchanger with counterflow
In case of cross-flow tube bundle heat exchanger, the two media flows in perpendicular direction to each other, thus the previously mentioned heating effect is mixed.
Fig. 7.9.
Inflexible tube bundle heat exchanger with cross-flow
Thermal expansion of inflexible tube bundle heat exchanger is limited. To achieve higher temperature, U-tube heat exchanger should be used, which is able to compensate developing internal tension by allowing thermal expansion of tubes.
Fig. 7.10.
U-tube heat exchanger Questions
1) What are the most common drug preparation operations that require heat transfer?
2) What are the principal methods and attributes of heat transfer?
3) What types of heat exchangers do you know of?
4) What are the possible types of heat exchange between the heating medium and the medium to be heated, according to their respective directions of flow?
5) To what type of flow does the Stefan-Boltzman law apply?
References
Banker G.,S.,. Rhodes Ch., T.: Modern Pharmaceutics, Marcell Dekker, Inc., New York, USA, 2002.
Langley A.,C., Belcher D.: Applied Pharmaceutical Practice, University Press, Cam-bridge, Great Britain, 2009.
Augsburger L.,L., Hoag S.,W.: Pharmaceutical dosage forms: Tabletts, Informa Healthcare, Inc. New York, USA, 2008.
Chowhana Z.T., Linna E.E.: Mixing of pharmaceutical solids. I. Effect of particle size on mixing in cylindrical shear and V-shaped tumbling mixers, Powder Technology,.24, 2, 237-244, 1979.
Aulton E.,A.: The Design and Manufacture of Medicines, Elsevier Ltd, New York, USA, 2007.
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