1. ERT 320 Bio-Separation Engineering Semester 2 2012/2013 Huzairy Hassan School of Bioprocess Engineering UniMAP

2. Product Formulation and Finishing Operations

3. “ Ability to evaluate process and polishing important parameters involved in purification and polishing steps of bio-products for selected bio-separation units ” Product Formulation and Finishing Operations

4. DRYING

5. -Usually last step in bio-separation process, which is the process of thermally removing volatile substances (often water) to yield a solid. -Reasons for drying a biological product:  It is susceptible to chemical (e.g., deamidation or oxidation) and/or physical (e.g., aggregation and precipitation) degradation during storage in a liquid formulation.  for convenience in the final use of product.  Although many bioproducts are stable when frozen, it is more economical and convenient to store them in dry form rather than frozen.

6. Drying Principle 1) Water in Biological Solids and in Gases -Water contained within biological solids is in 2 forms: Unbound or free water Bound water - is free to be in equilibrium with water in the vapor phase, - Thus, has the same vapor pressure as bulk water - is mainly held in the voids of the solid. - can exist in several conditions: 1)Water in fine capillaries that exerts an abnormally low vapor pressure because of the highly concave curvature of the surface 2)Water containing a high level of dissolved solids 3)Water in physical or chemical combination with the biological solids. - Solids containing bound water are called hygroscopic.

7. Drying Principle -The water content of the solid is plotted as a function of the relative humidity of air (Figure 10.1, for 3 products) -Humidity: the mass of water per mass of dry air. -The concentration of water, c w in moles per volume can be related to humidity, Ἥ and total pressure, p p w = partial pressure of water M = molecular weight R = ideal gas constant

9. Drying Principle -The relative humidity, R m, can be determined from p w and the saturation vapor pressure of water p ws as follows: -A convenient way of showing the properties of mixtures of air and water vapor mixtures is the humidity or psychrometric chart shown in Figure 10.2.

11. Drying Principle From Figure 10.2: -Any point on this chart represents a specific mixture of air and water. -The curved line denoted by 100 % represents the humidity of air saturated with water as a function of Temperature. -Any point below 100 % or saturation curve represents air that is unsaturated with water, and a point on the temperature axis represents dry air. -The wet-bulb or saturation temperature lines that slant downward from the saturation curve are called adiabatic cooling lines. -As T increases, the relative humidity decreases. - mole fraction of water & p w are contant as T rises, the p ws rises, thus causes R m to decrease.

12. Example 10.1 Drying of Antibiotic Crystals Air at 1 atm and 25 ⁰C with a relative humidity of 50% is to be heated to 50 ⁰C and then to be used in drying wet crystals of the antibiotic cefazolin sodium. The wet crystals contain 30 g of water per 100 g of dry antibiotic. In the drying process, the air at 50 ⁰C and the crystals reach equilibrium with respect to the moisture. Determine the following: a)The percentages of bound and unbound water in the wet crystals before drying, b)The moisture content of the crystals after drying, c)The water partial pressure at the drying temperature.

13. Drying Principle 2) Heat & Mass Transfer Heat Transfer - The principal heat transfer mechanisms:  Conduction from a hot surface contacting the material  Convection from a gas that contacts the material  Radiation from a hot gas or hot surface, and  Dielectric or microwave heating in high frequency electric fields that generate heat within the wet material.

14. Drying Principle 2) Heat & Mass Transfer Heat Transfer Conductive Drying Dominates in vacuum shelf dryers, batch vacuum rotary dryers, and freeze dryers -Heat is supplied through the surface of the dryer and flows into the solids being dried. - Either the solids on trays on heated shelves, or moving freely inside the dryer come in frequent contact with the surface of the dryer. Fourier’s Law: q = heat flux k = thermal conductivity y = the direction of heat flow

15. Drying Principle 2) Heat & Mass Transfer Heat Transfer Convective Drying Predominant in spray drying - Involves the transfer of heat from a moving gas phase, providing the heat for drying to a solid phase Q = rate of heat flow into solid A = surface area thru which heat flows T = gas bulk phase Temp. = Temp. at solid surface

16. Drying Principle 2) Heat & Mass Transfer Heat Transfer -For both, it is more convenient to describe the system by overall heat transfer coefficient, U: or using volumetric heat transfer coefficient, Ua:

17. Drying Principle 2) Heat & Mass Transfer Mass Transfer -Drying can be limited by mass transfer in convective drying. -The 1 st water to evaporate is that next to the gas moving across the surface of wet solids. -After an initial warming-up period, the rate of movement of water to the surface is rapid enough that the surface remains saturated, and the drying rate remains constant for a period of time called the “constant drying rate period”. -During this period, mass transfer is limited by a gas boundary layer at the surface of the solids. -At a critical moisture content X c, however, the internal rate of water movement is not fast enough to keep the surface saturated, and the drying rate begins to fall. -In the falling drying rate period, the drying rate asymptotically approaches the equilibrium moisture content X e.

19. Drying Principle 2) Heat & Mass Transfer Mass Transfer -The mass transfer of water being evaporated at the solid surface by gas flowing past the surface can be defined in terms of a mass transfer coefficient, k G : -During constant drying rate period, the steady-state relationship between heat and mass transfer at the liquid surface is: N w = molar flux of water Δp w = diff. in partial pressure of water between the surface and the bulk gas stream

20. Drying Principle 2) Heat & Mass Transfer Mass Transfer -Eq 10.2.13 allows us to estimate the evaporation rate if we know the heat transfer coefficient and the relevant temperatures. -The heat transfer coefficient has been found to vary from 10 to 100 kcal m -2 h -1 ⁰C -1 for forced convection of gas. -The temperature at the surface of a moist solid that is undergoing drying in the constant drying rate period is usually very nearly at the wet-bulb temperature, defined as the steady state temperature of a small mass of water that is evaporating into a continuous stream of humid air. -The wet-bulb temperature is very nearly equal to the adiabatic saturation temperature for air-water mixtures (Figure 10.2) on the curve denoted 100 %.

21. Figure 10.4 Drying rate curves for various types of materials and mass transfer conditions.

22. Drying Principle 2) Heat & Mass Transfer Mass Transfer During the falling rate drying period, the principal mass transfer mechanism are: 1) Liquid diffusion in continuous, homogenous materials, 2) Vapor diffusion in porous or granular materials, 3) Capillary flow in porous or granular materials, 4) Gravity flow in granular materials, and 5) Flow caused by shrinkage-induced pressure gradients.

23. Example 10.3 Mass Flux during the Constant Rate Drying Period in Convective Drying. Wet biological solids contained in a tray are dried by blowing air with 2 % relative humidity and at 60 ⁰C and atmosphere pressure across the tray. For the constant drying rate period, estimate the temperature at the surface of the solids and the maximum molar flux of water.

24. Dryer Description & Operation 1)Vacuum-Shelf Dryers

25. Dryer Description & Operation 1)Vacuum-Shelf Dryers -Trays filled with the product to be dried rest on shelves through which warm water or other suitable heat exchange medium is circulated. -Heat is conducted from the shelves to the trays and into the wet solids. -Vacuum is applied to the chamber containing trays to speed up the drying and allow drying to take place at lower temperature. -The evaporating water vapor is drawn off in the vacuum system. -Up to several square meters of shelf area. -Used extensively for pharmaceutical products such as antibiotics, which are often in crystalline from and exhibit moderate to high heat sensitivity.

26. Dryer Description & Operation 2) Batch Vacuum Rotary Dryers

27. Dryer Description & Operation 2) Batch Vacuum Rotary Dryers -Heat transfer is by conduction, also called vacuum tumble dryer. -Heat is supplied by warm water or other heat exchange medium circulated through a jacket on the rotating double-cone drum. -The solids are continually tumbled by rotation of the drum, so that solid particles comes in contact with the walls of the jacket and with each other. -Vacuum is applied to the rotating drum to be able to dry at lower temperature and more rapidly. -The volumes up to 30 to 40 m 3. -The biological products are like in vacuum-shelf dryer, but not when the tumbling motion causes the particles to form larger and larger balls or when the particles stick to the metal surfaces in the drum.

28. Dryer Description & Operation 3)Freeze Dryers Figure 10.7 Pharmaceutical Freeze Dryer

29. Dryer Description & Operation 3)Freeze Dryers -Requires both the temperature and pressure be controlled during drying process. -The product to be dried can be either in vials or in trays. -When the vials are placed on the trays, the stoppers are closed only partially to allow water vapor to escape. -The hydraulic piston allows for the stoppers to be completely pushed into the top of the vials at the end of drying. -A heat transfer fluid is circulated through the trays to provide temperature control of the vials.

30. Dryer Description & Operation 3)Freeze Dryers - Freeze drying process: 1 Cooling of the product to a sufficiently low temperature to allow complete solidification. The pressure in the chamber is then reduced to below vapor pressure at triple point of water (0.01 ⁰C and 4.6 mmHg) so that drying can occur by sublimation. 2 Thus the temperature of the shelves is raised to provide energy for sublimation. As drying occurs, a boundary between the dry solids and frozen solution can be observed in each vial (Figure 10.8). 3 Unbound water is removed in a drying phase called primary drying. A higher shelf temperature and additional time are required to remove the bound water in the secondary drying phase (Figure 10.9). Time to complete drying cycle: 24 to 48 h.

31. Dryer Description & Operation 3)Freeze Dryers

32. Dryer Description & Operation 3)Freeze Dryers

33. Dryer Description & Operation 3)Freeze Dryers - It is important that the product not exceed either eutectic temperature or the glass transition temperature. Otherwise the product can collapse. The temperature in crystalline systems below which no liquid exists. Exists only in amorphous systems and the temperature at which there is a change in viscosity of the system from a viscous liquid to a glass. Is the loss of either the crystalline or the amorphous structure of product.

34. Dryer Description & Operation 4) Spray Dryers Figure 10.10 Spray dryer with a pressure nozzle atomizer: 1-feed tank, 2-filter, 3-pump, 4- atomizer, 5-air heater, 6- fan, 7- air disperser, 8- drying chamber, 9- cyclone, 10-exhaust fan, 11-filter.

35. Dryer Description & Operation 4) Spray Dryers -Transform a feed in the liquid state into a dried particulate form by spraying the liquid into a hot gas, usually air. -Utilize co-current flow of gas and feed. -3 basic unit processes involved: liquid atomization, gas-droplet mixing, and drying from liquid droplets. -Spherical particles produced; either solid or hollow, range in size from 2 µm to more than 500 µm. -Drying is carried out at the air wet-bulb temperature, and drying time is measured in seconds. Inlet gas temp. can range from 150 – 250 ⁰C. -Applied in producing milk, coffee, blood, spores and antibiotics.

36. Dryer Description & Operation 4) Spray Dryers -Most important operation: Atomization -Types of atomizer determines the size and size distribution of drops and trajectory and speed. -3 types of atomizer: 1) rotary wheel (centrifugal disk), 2) pressure nozzle single-fluid 3) pneumatic two-fluid nozzles -Rotary wheel atomizer prefers for high flow rate feed streams (>5 metric tons/h), produces relatively small particles (30 – 120 µm)

37. Scale-up & Design of Drying Systems 1)Vacuum-Shelf Dryers -The effect of changes in conditions upon scale-up can be estimated using the time of conductive drying: -The thermal efficiency is usually between 60 % - 80 %. -Power can be estimated based on power to operate vacuum system; 0.06 to 0.12 kW/m 2 tray surface area for vacuums of 680 – 735 mmHg.

38. Scale-up & Design of Drying Systems 2)Batch Vacuum Rotary Dryers - In scaling-up, the heated surface area per internal volume is not constant. -Ex: if we assume the dryer is a perfect double cone, the heated area increases by a factor of 4.6 when the volume increases by a factor of 10 for geometrical similarity. -Meaning  the ratio of area to volume at large scale is 46% of the area-to-volume ratio of small scale unit with the volume -Assuming time for drying is inversely proportional to the area-to-volume ratio of dryer:

39. Scale-up & Design of Drying Systems 3)Freeze Dryers -Design conditions (as in Figure 10.9), determine; 1) The max allowable temperature during primary drying, using Differential Scanning Calorimetry (DSC) 2) Chamber pressure, shelf temperature and time for primary drying. 3) Chamber pressure and shelf temperature for secondary drying.

40. Scale-up & Design of Drying Systems 4)Spray Dryers -Key variable: residence time of the air in drying chamber -Residence time = chamber volume / total air flow rate -Average air residence time ≈ 35 s -Assumptions: 1) Drying conditions are uniform throughout the chamber 2) Drying occurs from the drop surface 3) The h (convective heat transfer coefficient) determined by assuming a representative drop is motionless fluid, with the drop moving at the same speed of air.

41. Please study and solve this on your own Example 10.5 Sizing of a Spray Dryer Estimate the dimensions of a drying chamber for a spray dryer that has an output of 1000 kg/h of a heat-sensitive biological material at 60 ⁰C containing 5 % moisture and having a mean particle size of 100 µm. The feed contains 40% solids by weight in an aqueous solution at 4 ⁰C. The inlet air has a humidity of 0.01 kg/kg dry air and is at 150 ⁰C, while the outlet air is at 80 ⁰C. Assume the specific heat of dry solids is 0.3 kcal kg -1 ⁰C -1.

42. ANY QUESTIONS THANK YOU