amixon GmbH Halberstädter Straße 55

D-33106 Paderborn Phone: +49 5251 68 88 88-0 Fax: +49 5251 68 88 88-999

info@amixon.com www.amixon.com

FILTECH 2015 – February 24-26 2015 amixon GmbH – Booth B11 – Hall 11.1

amixon vacuum mixer-dryers and reactors

A number of different stages of synthesis are involved in the manufacture of pharmaceutical

agents. Whenever the synthesis results in flocculation or crystallisation of the desired product

it is subsequently necessary to wash the products with alcohol, acetone and/or with water or

with an aqueous solution. The washing process is most often followed by a mechanical

drying process, which takes place, as a rule, in centrifuges or pressure suction filters.

Because it is not possible to achieve the necessary desiccation ratio (TS greater than

99.95%) with this step alone, a more intensive, thermal drying stage is required. Convection

or contact dryers are used here. Contact dryers are most often used if the materials require

handling of a sort that will entail extremely little contamination. Contact dryers are also

preferred if the materials do not adopt unusual consistencies in the course of the drying. The

usual design of contact dryers includes a temperature-controlled boiler in which a mixing

gear rotates at high or low speed. A distinction is made between contact dryers whose

mixing shaft is oriented horizontally, vertically or inclined.

As an example of the horizontally oriented equipment we might mention here the classic

paddle-through or ploughshare dryers, particular versions of which have been produced by

various manufacturers. For decades, this design has been the standard dryer used both in

pharmaceutical manufacturing processes and in the chemical industry. In the meantime, new

types of mixer-dryers have begun to replace the classic paddle-through dryer; these are

dynamically operating vertical single-shaft mixer-dryers, such as those already successfully

introduced to the market by amixon® GmbH.

amixon® - vacuum mixer-dryers and reactors have a vertical helical band mixing gear. This

rotates within a thick-walled, round cylinder with a flat base, passing extremely close to the

walls and floor. The very high equidistance between the mixing gear and the fully heated

walls guarantees ideal thermal transfer, reliably avoiding wall adhesions. The special shape

of the helical spring creates mixing and flow, without compacting or pressing the materials. It

is of particular significance that all the surfaces of the mixing gear are also temperature-

controlled; the shaft of the mixing gear, the shovel-like arms and the helical spring.

Substantially shorter drying times So far, amixon® has replaced 30 horizontal paddle-through dryers with vertical dryers. These

are industrial dryers for pharmaceutical agents such as penicillin, analgesics, cardiac

medications and X-ray contrast media, as well as chemicals such as herbicides, fungicides,

adhesive glues and ceramic pigments. The batch sizes vary from 50 litres up to 18,000 litres.

According to the experience of the operators, the use of amixon® vacuum mixing-dryers can

enable the usual drying times of paddle dryers to be reduced by more than 40 %. The reason

for this is that the flow of the material to be dried extends throughout the entire chamber -

thanks to the patented mixing gear there are no dead spaces.

As on the other hand the mechanical energy input (drive power at the mixing tool) is

substantially lower, it is obvious that the exchange of heat and material takes place more

effectively. The goods to be dried are conveyed vertically in the periphery of the mixing

chamber by the helical spring and slide downwards in the centre, following the laws of

gravity. Static mixing tools prevent the rotation of the goods by combing with the rotating

mixing tool.

Laboratory and Trials

The Alloy and Hastelloy drying equipment in the amixon® laboratory is already part of the

apparatus manufacturer's standard equipment. This offers a major advantage to all

manufacturers and future customers interested in experimental trials: all products can be

tested in their true form; it is not necessary to make use of a dummy product. amixon®

mixer-dryers and reactors have hygienically designed CleverCut®-inspection doors, which

make the access for inspection and cleaning purposes much easier. The internally located

filters allow valuable building height to be saved, as does the equipment's compact

construction.

Safe design of large dryers

amixon® has profound practical experience with various drying goods and processes. For

example, the amixon®-engineers have developed an upscale programme based on

knowledge gained from thermodynamic experience, in order to be able to reliably base large-

scale dryer mixing results on experience from mixing tests. This means that amixon is able to

predict processing times and provide process guarantees on the basis of test results.

Also suitable for goods with delicate rheological properties

During the drying process, the most various consistencies occur at various stages. Beginning

with the pumpable suspension, the product characteristics change as the drying process

progresses. The products become increasingly less capable of flowing, compact and even

sticky, tough and pasty. In the next phase they become crumbly and form granulate, which at

a later stage is further reduced with the loss of moisture – until a finely dispersed powder

emerges.

Aqueous suspensions also develop tough and pasty consistencies. The mass can then be

compared with the viscosity and stickiness of chewing gum. Depending on the product,

classical rheological phenomena, such as shear thinning or shear thickening occur. These

states are difficult to handle from a processing point of view and pose high demands on the

dryer stability. Adhering to the mixing tool, the mass tends to follow the mixing tool rotation.

This, however, would interrupt the material and heat exchange.

Reliably controlling and effectively kneading viscoplastic products

Typical kneading properties of the amixon®-dryer are applied here, in which static and

dynamic mixing tools comb together. The mass is pulled apart at reduced mixing tool speed,

new surfaces are opened and dried, and the strands that were pulled apart join together

again, only to be pulled apart again afterwards. This way, the plastic mass is kneaded and

effectively dried with no dead space.

Crystalline materials, which are often found as initial pharmaceutical products, represent a

special case. Due to their crystalline structure they are not easily mixed and it is difficult to

generate a flow in the mixer. On the other hand, the mechanical or thermal input of energy

involved in the drying process must not damage the crystalline structures.

The amixon® vacuum mixer-dryer rises to this task magnificently. The process materials are

screwed upwards at the periphery of the container by the mixing gear, and flow down along

the shaft again under the influence of gravity. Moreover, this kind of mixer can be operated

with variable circumferential speeds from > 4 ms-1 to < 1 ms-1, as this does not affect the flow

without dead spaces.

The ability to choose circumferential speeds, when required, of < 1 ms-1 has another crucial

advantage for many companies: if dust or solvent can give rise to a risk of explosion in the

equipment as it is started up or shut down under atmospheric conditions, it is possible to

lower the circumferential velocity in order to satisfy the need for safety (see here also ATEX

94/2/EG).

The drive, the bearings and the seals for the mixing gear shaft are all above the mixing

chamber. Thermal expansion and mechanical stress do not have any effect on the face seal.

Both high excess pressures and high-quality vacua are sealed with extremely little leakage.

This reliably protects the environment of the mixer-dryer from the materials reacting within

the equipment, and at the same time lowers operating costs and preserves the purity of the

materials.

Hygiene and Cleaning

amixon® equipment is designed and built in accordance with the most recent EHEDG

guidelines, and conforms to GMP and FDA requirements. It can be used in all areas of the

pharmaceutical industry. For apparatuses that need to be operated under sterile conditions

(e.g. penicillin manufacture) amixon® has developed techniques and special solutions

particularly for this purpose.

For an automatic wet cleaning, amixon® can provide the „WaterDragon®“–system. The

washing lance moves automatically into the mixing chamber. Driven by the water pressure,

the washing head rotates and the nozzles spray the complete process apparatus. Once the

process is completed, the rotating washing lance returns to the parking position and seals

the processing chamber gas-tight and liquid-tight.

Vertical mixer with conical base for very thorough emptying of residues

If it is important to have very high residual emptying rates, the amixon® conical mixers and

mixer-dryers are particularly appropriate. Together with the patented "sliding blades", the

conical base ensures residual emptying rates of up to 99,9%. With the "sliding blades", the

mixing gear is tilted to a horizontal position. This improves removal of the product residues.

Otherwise, the same requirements related to and governing the technical aspects of the

process apply as have already been described for the vertical vacuum mixer-dryers with flat

bases.

Quality and service

All components of the amixon®-mixers are made in Germany. The production of the

machines takes place exclusively in the amixon®-factory in Paderborn, Germany.

For the testing of mixing and drying processes, amixon® runs the test centers in Paderborn /

Germany, Memphis / USA and Osaka /Japan. Further amixon® test centers are located in

Bangkok / Thailand and Satara / India.

In addition to the equipment itself, amixon® offers assistance with the qualification of the

supplied equipment as a service. All the necessary documentation is drawn up, and

qualification of the installation is carried out in co-operation with those who will later operate

the plant.