WO2006120117A1

WO2006120117A1 - Reactor and method for gentle product drying

Info

Publication number: WO2006120117A1
Application number: PCT/EP2006/061791
Authority: WO
Inventors: Andreas Karau; Manfred Dannehl; Kai Boldt; Ansgar Oelmann
Original assignee: Degussa Gmbh
Priority date: 2005-05-13
Filing date: 2006-04-24
Publication date: 2006-11-16
Also published as: DE102005022154A1

Abstract

The present invention relates to a reactor and a method for drying thermosensitive products, inter alia. The method can be applied with very particular advantage to drying temperature-sensitive material such as, for example, cells, biocatalysts, polysaccharides etc. The method works with a reactor which has a first unit which is capable of specifically generating droplets which have the said product. The droplets traverse an electromagnetic radiation field in which they are dried by means of energy input. The solid sample is subsequently collected.

Description

Reactor and method for gentle product drying

The present invention relates to a reactor and a method for gentle drying of sensitive organic materials. In particular, the invention is directed towards a method in which small droplets containing the sensitive organic material are generated which are heated without contact by an electromagnetic alternating field and are thereby freed from the solvent or suspension medium.

The gentle drying of sensitive organic materials plays a decisive role, in particular, in the drying of biological materials (for example cells, proteins, polysaccharides etc.), since these compounds, which are required for various biotechnological applications, are generally capable of having a long shelf life only if they are stored in the frozen state or when dry.

The drying of temperature-sensitive biological material is generally known. So-called freeze drying is the most common method in this field. This method is preferably applied because the products in question suffer a loss of activity at an excessively high temperature, and so drying under "normal" conditions is ruled out.

However, the method of freeze drying is a lengthy and very energy-intensive undertaking. It therefore appears to be disadvantageous, at least on the technical scale, from the economic and ecological points of view.

DE 2822370 discloses a method for producing solid particles in which solid particles are produced from droplets of a flowing medium by the action of microwave radiation. The method described here cannot be applied to the drying of, for example, biological materials, since the action of microwave radiation results in excessive heating of the material, and this can cause their deactivation. The method illustrated is thus also primarily applicapable to materials such as biologically harmful waste, synthetic resins and nuclear fuel materials in the case of which heating of the samples is to be seen as less critical.

The method described in DE 3826047 for drying finely divided solids works at temperatures of above 700 degrees Celsius, preferably in the range from 800 to 1000 degrees Celsius. Such temperature ranges are unsuitable for drying biological material which is to retain its biological activity after drying.

It therefore remains a concern of research to make available further methods for drying sensitive materials, in particular.

It was therefore the object of the present invention to find a further possibility which permits temperature- sensitive products such as, for example, biological materials, to be freed from adhering residues of suspension media and/or solvents in a way which is as gentle as possible, but yet advantageous against the background of the prior art. With reference to the use of the method according to the invention in the case of biocatalysts (enzymes) , particular attention is to be directed to the fact of retaining the activity of the biocatalysts to be dried, without losing sight of the drying costs in so doing.

The object is achieved in accordance with the claims. Claim 1 relates to a preferred apparatus for drying. Claims 2 to 4 are directed towards preferred embodiments of the drying apparatus . Claim 5 covers a method according to the invention while Claims 6 to 15 relate to preferred embodiments of the present method. By making available a reactor for drying products otherwise solid under the environmental conditions and which has a) a first unit which produces falling drops containing the product in at least suspended form, b) a reactor through which the drops can fall without contact in the longitudinal direction and which is at least partially transparent to electromagnetic radiation in the IR, optionally also in the UV and VIS region, c) an electromagnetic radiation source which is capable of applying electromagnetic radiation of the IR, optionally of the UV and VIS region to the falling drops, and d) a last unit for collecting the solid products after passage through the electromagnetic radiation field, the object set is achieved in an extremely advantageous way which is, however, no less surprising. The reactor presented permits the energy for the removal of the solvent and/or suspension medium to be transmitted without contact by IR, optionally by UV and VIS radiation and thus, without excessively high thermal stress, to dry even sensitive or thermally unstable products without the risk of baking the solid product constituents and with surprising efficiency, as conditioned by the high energy coupling. In the field of drying biocatalysts, these advantages are manifested in the fact that, by comparison with known freeze drying, the economic indices for the method and the costs of energy usage appear decidedly favourable in conjunction with a measure of retention of activity which is otherwise equivalent or even better.

The reactor can be configured as decided by the person skilled in the art under the boundary conditions addressed above. It should exhibit at least one region which is transparent to IR, optionally to UV and VIS radiation, and through which the drops generated can fall in such a way that they are detected by the emitted radiation in a fashion as far as possible without coming into contact with the wall of the reactor before the end of the drying process. Under these boundary conditions, a reactor which is configured in the shape of a tube (precipitation column) appears to be advantageous . The drops enter the reactor at the upper end thereof and traverse the subregion transparent to radiation, in which the drying of the material takes place. Subsequently, the dry material is collected at the outlet of the reactor by suitable apparatuses.

The drying can be performed in a very particularly gentle fashion when, in addition to the supply of energy by an IR, optionally an UV and VIS radiation source, the drops are exposed at the same time to a vacuum. The solvent or suspension medium present can in this case be converted into the gas phase at even lower temperatures, and thus more gently. Consequently, it is particularly advantageous to connect the reactor according to the invention to a vacuum pump in such a way that the drops generated are exposed to a vacuum at least up to the desired drying. If oxidation-sensitive materials are involved for the purpose of being dried, the entire apparatus can be put under a protective gas if desired. Simple nitrogen or inert gases such as helium or argon, in particular, are suitable here as protective gases.

The first unit of the reactor according to the invention comprises, as already set forth above, a unit which is capable of generating drops which include the material to be dried, at least in suspended form. The expression "at least in suspended form" is to be understood according to the invention such that the material to be dried can also be present in the drop in a fashion completely dissolved (homogeneously dissolved) , partially dissolved or suspended. Methods for generating correctly dimensioned drops are known in principle to the person skilled in the art (Lord Rayleigh: On the instability of jets; Proc. Lond. Math. Soc. 10, (1878), R. Bϋttiker: Erzeugung von Suspensionstropfen gleicher Grδβe und deren Trocknung zu einheitlichem Granulat [Generation of suspension drops of equal size and drying them to form uniform granules] ; CHIMA 31 (1977) , No. 8)

It is preferred for the first unit of the reactor according to the invention which been addressed here to be equipped with a so-called piezoceramic oscillator for drop generation. Such apparatuses for drop generation are likewise sufficiently well known to the person skilled in the art (Yang et al . : A simple piezoelectric droplet generator; Exper. in Fluids 23 (1997) 5, 445/447) . When liquids flow out from tubular nozzles, laminar liquid filaments are firstly formed which disintegrate into drops at a short distance from the exit point. The resulting drops have a virtually monodisperse drop size distribution. Depending on the Reynolds ' number and the excitation frequency, a wide spectrum of monodisperse drop diameters can be generated by exciting the beam with a superposed disturbing frequency which corresponds to the optimum wavelength. The excitation can be performed, for example, by means of a piezoceramic oscillator which is driven via a frequency generator. The atomizer design of such a system is illustrated in Figure 2.

The apparatus just described for generating drops can advantageously be coupled to an electro-optical system which permits the detection of the size and generating frequency of the drops . Such electro-optical systems are sufficiently well known to the person skilled in the art. To this end, the drop disintegration is detected, for example, via a triggered CCD camera with short shutter intervals. It is useful in this case to use a long-distance microscope in order to observe the drops. Triggering is performed via a stroboscope situated opposite the camera. This arrangement can be used to observe drop disintegration, and the formation of smaller satellite drops can be avoided.

Likewise, the subject matter of the invention is a method for drying products otherwise solid under the environmental conditions by means of a) generating falling droplets containing the product in at least suspended form, b) introducing the droplets into an electromagnetic radiation field of the IR, optionally also of the UV and VIS region, c) collecting the resulting solid products after passage through the electromagnetic radiation field.

By comparison with the methods of the prior art, the method represented here has the advantages addressed above for the apparatus. The definitions made above and preferred designs are valid here correspondingly.

Although the present method can be used to carry out any sort of drying of at least suspended material, the method can be applied with the advantages addressed above in a very particularly effective way to materials which react sensitively with regard to the introduction of gravity forces or thermal stress. It is therefore extremely preferable to use the present method for drying homogeneously or heterogeneously dissolved temperature- sensitive, in particular biological, materials. Materials with biological activity, for example antibodies, enzymes, sugars, nucleotides, bioactive agents for cosmetic applications, foodstuff additives etc., in particular, come into consideration as biological material.

As already indicated above, it is particularly advantageous to control the generation of drops by means of a piezoceramic oscillator. The driving can advantageously be carried out such that, as already indicated above, the oscillator is coupled to an electro-optical system in such a way that the formation of drops can be specifically controlled with regard to frequency and size. It follows that what has been said above with reference to this point is valid.

Energy in the form of electromagnetic radiation in the IR, optionally in the UV and VIS region is applied to the falling drops. The dissipative energy coupling thereby taking place leads to evaporation of the adhering solvent or suspension medium, and thus to a dry product which is discharged at the end of the reactor by suitable apparatuses . The feeding of energy in the form of electromagnetic radiation is preferably performed in the wavelength region of 172 - 12 000 nm, that is to say in the IR, optionally in the UV and VIS region. The wavelength region described below for water as solvent is more preferably used. This suffices for the purpose that, for example, the loss in activity of biocatalysts dried in such a way turns out to be surprisingly slight by comparison with the crude solution. Thus, for example, by comparison with the starting material before drying, residual activities of greater than 77% are still to be recorded when drying biocatalysts as far as a residual moisture of virtually 0% in the case of an emitter temperature of 400 degrees Celsius and a pressure of 30 mbar.

When biological materials are being dried, the wavelengths of the electromagnetic radiation used should be dimensioned such that optimum drying is possible in conjunction with the least possible loss of activity under the conditions given above. It is advantageous when a wavelength of the electromagnetic radiation is tuned to the absorption properties of the solvent to be removed. In the case of water, for example, the IR absorption maxima lie at 3 μm and 6 μm. Consequently, it is preferred to use a wavelength of 0.5 - 10 μm for drying aqueous systems. For this example of application, it is preferred to use a wavelength of 0.5 - 6 μm and, very particularly preferably, one of 0.5 -

3 μm. The optimum wavelength to be used depends greatly on the material to be dried and on the solvent or suspension medium used.

It can likewise be advantageous to facilitate drying by applying a vacuum. The vacuum can be achieved by connecting a vacuum pump to the reactor accoridng to the invention (see above) . Vacuums of 1 - 100 kPa, preferably 10 - 80 kPa, are advantageously set.

In order not to damage biological material during drying, the power of the radiation source is set to the maximum tolerable product temperature and drying time. Empirically, the energy densities to be set lie between >0 and

2.5 MW/m², preferably between 10 - 250 kW/m², and very particularly preferably between 20 - 100 kW/m².

Emitter temperatures from 200⁰C to 2600⁰C thereby result. Preference is given to emitter temperatures from 200 to

1000 degrees Celsius, preferably 200 - 800 degrees Celsius, and very particularly preferably around 400±100 degrees Celsius .

The droplet size has a deciding influence on the quality and rate of drying of the material introduced. It is a function of the material to be dried and is set by the person skilled in the art with regard to efficiency of the drying in conjunction with optimum energy input. A droplet size of 10 - 5000 μm is advantageous. The drop size can further advantageously be set between 10 - 800 μm, very advantageously between 10 - 100 μm, and extremely advantageously between 30 - 60 μm.

As already indicated, the thermal stress suffered by the product to be dried should be kept as slight as possible, at least in the case of thermally unstable substances . Consequently, it is of entirely particular advantage when drying such materials that a product temperature of below 100⁰C can be set in this case as far as possible by setting the above known parameters . In the case of biocatalysts intended to be dried using the method according to the invention, it is to be recommended to set a temperature of below 80, more preferably of below 70, and very particularly preferably of below 60 degrees Celsius.

In addition to the advantages of the method according to the invention which have been addressed above, it is particularly remarkable that, by contrast with other drying methods such as, for example, freeze drying, the present drying method can be operated continously. The procedure here is advantageously that the droplets generated by the drop generator are introduced continuously into the drying reactor and are withdrawn continuously at the outlet. This can be performed via suitable sluice systems, for example.

An experimental setup according to the invention can be described as follows: the monodrop atomizer device is mounted at the upper end of a reactor according to the invention (Figures 1/2) . The drops generated move in the terrestrial gravity field through the IR/ (UV and VIS) drying path, are collected at the lower end in a vessel, and can be continously sluiced out after the drying. Reaction/inert gas can be applied to the possibly gastight reactor via appropriate gas connections, and the desired atmosphere can be set.

As illustrated in Figure 1, the reactor according to the invention can have a DNlOO tubular stage of length 1.5 m and is heated from outside with the aid of IR/ (UV and VIS) emitters. Heat is transferred to the product located in the reactor without contact. The electromagnetic radiation is dissipated directly in the drops as heat. The reactor wall (here quartz glass) remains virtually cold. The rates of heat flow can be regulated very accurately via the emitter wavelength and the lamp power, and the drying conditions can thereby be set. The temperature measurement and regulation can be performed pyrometrically (Pyrometer Handbuch [Pyrometer manual] , company document from IMPAC Infrared GmbH, 2004) .

The IR radiation can be set steplessly with energy- densities of, for example, 0 to 250 KW/m² (correlation see above) and thus be tuned specifically to the drying and/or reaction properties of the drops generated. Each drop is exposed to the same conditions owing to the monodisperse distribution. Even temperature-sensitive products can be dried effectively at very low temperatures (< 5O⁰C) in the case of drying in vacuum.

Method parameters of IR monodrop dryers according to the invention can be:

• Drop size spectrum 10 - 5 μm monodisperse

• Production temperature regime: 3O⁰C- 95O⁰C

(temperature gradients are possible)

• Pressure regime: 1 mbar - 1.5 bar abs .

• Atmosphere freely selectable (inert/solvent)

The advantages achieved are:

• Closed reactor system contamination free drying/heat treatment (-> GMP possible)

• Identical reaction conditions for all particles, equal particle size and equal dwell time in the reaction space. • High space-time yield owing to compact design and specific energy use (up to 10 kg 200 μm powder/h in the plant described) .

• Setting the (particle) product morphology by means of setting the drying rate.

• Drying under a solvent atmosphere without a carrier gas stream

• Gentle drying/heat treatment for temperature-sensitive products .

The advantages set forth are surprising against the background of the prior art, and therefore not obvious.

Description of the figures:

Figures 1/2

1 Vacuum pump 5a Pressure/temperature sensor

IR emitter 6 Optional filter

3 Camera Piezoceramic oscillator

3a Computer/imager 8 Generator

4 Drop generator 9 Stroboscopic lamp

5 Reservoir 10 Removal unit

The material to be dried is fed from the reservoir 5 into the drop generator 4 via an optional filter 6. The generator 8 breaks up the material to be dried into individual drops in the drop generator 4 by means of the piezoceramic oscillator 7. The generation of the drops is observed via the camera 3, which is locked on the other side of the apparatus, through a stroboscopic lamp 9. The generation of the drops can be controlled specifically via the computerized control loop 3a-8-7. The drops fall through the IR/ (UV and VIS) -transparent part of the reactor in which electromagnetic radiation is applied to them by the IR/ (UV and VIS) emitter 2. The dried product is collected in the unit 10 and, if appropriate, removed. If required, the plant according to the invention can be connected to a vacuum pump 1 in order to be able to perform the drying in a vacuum. Procedure

In order to clarify whether a vacuum IR drying method is also possible in a continuous apparatus. The apparatus explained in Figure 1 was constructed for this purpose.

It is advantageous here that all the drops have the same drying kinetics owing to the generation of a monodisperse spray. Consequently, the irradiated radiant power can be matched exactly. A vacuum is advantageous for drying sensitive products in order to keep the evaporation temperature of the water low and not to overheat the particles .

The apparatus is placed in a defined vacuum by comparison with the surroundings by being connected to a vacuum pump. The solution to be dried is filled into the storage vessel, and a specific overpressure which is responsible for the exit speed of the jet is applied to the vessel by adding compressed air. The piezoceramic oscillator is excited with the aid of a frequency which is tuned to the exit speed and the nozzle geometry used. The monodisperse spray generated by means of this excitation passes into the quartz glass tube, where IV radiation is applied to it, the solvent being converted into the vapour phase. The material is collected by a filter.

Exemplary method

The first experiments were carried out with BSA solution having a concentration of 25% by weight.

Good results were attained with a nozzle having 7 bores

It emerged that for the BSA solution it is possible for drop sizes of 94.5 μm and 189 μm to be effectively dried in the apparatus. For this purpose, nozzle diameters of 50 μm and 100 μm are necessary. Figures 3 and 4 present particles which have been dried with the aid of these settings .

Examples : Biomass was introduced into a vacuum-proof vessel. Once a defined vacuum had been applied, the IR emitter was switched on at the temperature specified in Table 3, and the biomass was dried until it was no longer possible to establish any weight loss over a period of 60 min. The residual activities obtained lie between 40 and 77%.

Table 3: experimental parameters and residual activity

Comparison of the methods of monodrop atomization/freeze drying/spray drying

In addition to the abovedescribed method of monodrop atomization/radiation drying, freeze drying or classical spray drying can also be used to remove water and thus preserve the enzyme solutions or biocatalysts . However, a very high residual moisture is to be expected in the product when in the course of spray drying the temperature limits of <50°C product temperature (dryer output temperature) are adhered to. Furthermore, it is not possible to avoid overheating, above all of the smaller drops, in the event of a wide drop distribution. Consequently, the method of classical spray drying is not to be recommended here.

The advantages of the monodrop atomization with subsequent radiation drying in a vacuum as compared with freeze drying are presented in the following Table 4.

Table 4 : Comparison of the methods of freeze drying and monodrop atomization

Claims

Patent Claims :

1. Reactor for drying products otherwise solid under the environmental conditions, having a) a first unit which produces drops containing the product in at least suspended form, b) a reactor through which the drops can fall without contact in the longitudinal direction and which is at least partially transparent to electromagnetic radiation in the IR, optionally also in the UV and VIS region, c) an electromagnetic radiation source which is capable of applying electromagnetic radiation of the IR, optionally of the UV and VIS region to the falling drops, and d) a last unit for collecting the solid products after passage through the electromagnetic radiation field.

2. Reactor according to Claim 1, characterized in that the said reactor is connected to a vacuum pump.

3. Reactor according to one or more of the preceding claims, characterized in that the first unit has a piezoceramic oscillator for drop generation.

4. Reactor according to Claim 1 and/or 2, characterized in that the first unit has an electro-optical system for controlling drops .

5. Method for drying products otherwise solid under the environmental conditions by means of a) generating falling droplets containing the product in at least suspended form, b) introducing the droplets into an electromagnetic radiation field of the IR, optionally also of the UV and VIS region, c) collecting the resulting solid products after passage through the electromagnetic radiation field.

6. Method according to Claim 5, characterized in that the solid products are temperature-sensitive, if appropriate biological, material.

7. Method according to 5 and/or 6, characterized in that the generation of drops is controlled by means of a piezoceramic oscillator.

8. Method according to one or more of Claims 5 - 7, characterized in that the formation of drops is controlled by means of an electro-optical system.

9. Method according to one or more of Claims 5 - 8, characterized in that electromagnetic radiation of wavelength 172 - 12 000 nm is used

10. Method according to one or more of Claims 5 - 9, characterized in that the drying is carried out at a pressure of between 1 - 100 kPa.

11. Method according to one or more of Claims 5 - 10, characterized in that an IR (UV and VIS) power of >0 - 2.5 MW/m² is applied

12. Method according to one or more of Claims 5 - 11, characterized in that the emitter temperature is set between 200⁰C and 2600⁰C

13. Method according to one or more of Claims 5 - 12, characterized in that a droplet size of 10 - 5000 μm is set.

14. Method according to one or more of Claims 7 - 13 in the case of drying temperature-sensitive material, characterized in that the product temperature is kept below 100⁰C.

15. Method according to one or more of Claims 5 - 14, characterized in that the process is operated continuously.