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.
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.
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.
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.
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.
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.
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.
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.
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.