Application of the newest technological solution in production of pharmaceuticals, has become a necessity. However, desire for profit and winning as many customers as possible, unfortunately causes process machinery manufacturers to offer a technology which does not meet the requirements and even their own declarations. How much truth, a half-truth and marketing tricks is in their assurances ?
Very often, the most important parts of the machine are based on the solutions, which has already become insufficient and even dangerous for the pharmaceutical product, because of technological progress in this industry branch. Despite this fact, many process machine manufacturers still build their devices basing on the solutions which should never be offered for pharmaceutical industries. “GMP” is treated by them as a “magic key”, which shall open all the doors to customer.
For many years in Poland we can observer growing quantity of “western” process machinery manufacturers for pharmaceutical industries, used to process wet form products i.e. emulsions, gels, ointments, etc. While fighting for the customer, they try to convince him, that their technology is the best, the most innovative and in accordance with the newest trends. Often they underestimate the state of Polish technologists knowledge, who are known to be the leaders among new generation pharmaceuticals creators. Nowadays, within their reach, there are high quality process machines made in Poland – similar were only available in Germany – country which is an undisputed leader in this field.
The most common purely commercial trick is to lower the minimal useful volume of a mixer. It is not true that one can achieve a stable emulsion at 10% of maximum useful mixer capacity. This is due to the fact that considering the technological assumption of high shear force, therefore high efficiency of homogenizer and stirrer, a very negative phenomena such as cavitation, can occur – it is dangerous for the product as well as machine itself. It also has bad influence on homogenization effectiveness and accuracy of product averaging, which can cause instability of the final product.
In accordance with our calculation, the minimal useful volume, which can be assumed as an optimal in production of e.g. emulsion is ca. 30% of maximum useful volume, taking into consideration the fact that homogenizer as far as its efficiency, is comparable to the best one, manufactured by world leaders.
It is not true, that only process mixers equipped with contra rotating stirrers are able to average high viscosity products accurately. Application of anchor stirrer with properly phased baffles, including static wave breakers, enables to achieve even better mixing effect in shorter time, regardless product viscosity. Thanks to simplification, such construction of the stirrer, has good influence on product quality and does not cause microbiological contamination threat. Contra rotating stirrers do not guarantee it – these obsolete solutions, because of their construction, do not give full warranty of product protection against contamination which comes from the mechanical sealing, bearings or sleeves. If there is vacuum and high temperature inside the vessel, these contaminations will be sucked into production zone, thus into product. Many times, during servicing and renovations of such kind of mixers, when replacing the bearing sealings, old product was found – often remaining there from the first batch or the last renovation. The worst thing is, regardless type of the sealing, after ca. 2-3 months of intensive work, they will become ineffective and the product sooner or later will penetrate inside them. There are few basic rules which should be considered by stirrer constructor:
- no dead zone inside production area of the mixer, especially near the stirrer shaft
- reduced number of stirrer elements
- design enabling to mix the product in vertical and horizontal directions as well as its recirculation (which is very important for proper averaging without homogenizer)
An element which do not allow user to perform a proper validation is homogenizer driven by belt. Such solution applied to process machine, does not guarantee repeatability of the designed tip speed of homogenizer, which leads to a problem with repeatability of the technological formula for specified product. The also cause contamination of the production area because of the belt natural wearing tendency. Unfortunately, such machines are often used in pharmaceutical industries, placed in clean zones “C” or “B”, whereas they should not be allowed to be placed even in lower class rooms. The optimal solution is vertical homogenizer installed in the vessel bottom and direct power transmission from the motor shaft. It is not uncommon to find horizontal position of homogenizer, which makes product recirculation difficult – especially high viscosity and density products. Therefore, in order to help such homogenizer, some European manufacturers use additional mini-propellers and lobe pumps, which are supposed to help homogenizer by pumping it into its chamber. Despite such solution, homogenizing effect is still limited because of too long distance between vessel and homogenizer, and the above mentioned additional elements will become problematic during cleaning, servicing and fixing. Therefore, homogenizer should be designed in such way, its installation would be possible in the process mixer bottom center, and no other elements inside homogenizer chamber. At the same time, because of high viscosity or density of the product, it must guarantee efficient homogenization on every stage of production process – at high as well low temperatures. This versatility is especially important when technology requires introduction of one of the components in such moment, product becomes very viscous. In case homogenization is performed only inside the vessel, machine will not be able to guarantee proper averaging of the bulk, which is unacceptable, especially when API is to be introduced into the vessel. Averaging and making final product homogenous in its whole volume is the most important thing and only homogenization with external recirculation by-pass can guarantee it.
Not meaningless is also the vessel shape. Often there are vessels with conical bottoms, which are assured by manufactures to provide more efficient homogenizer wort, which only a half-truth. In fact, it is all about making easier for the product to flow into homogenizer with help of gravity. This supposes to ensure recirculation, when the product becomes very viscous. It’s especially important in case of horizontal homogenizer. However, the most often a conical bottom is used, when homogenizer parameters are not enough to properly homogenizer the high viscosity product. Conical bottom for production of viscous products is a bad idea, because in case only stirrer can be used, the whole process will be ineffective. At ca. ¾ of bottom volume, product recirculation bottom-top, top-bottom, is not efficient, which results in bad quality, not homogenous product. Every product containing API, especially when added in low temperature, must me well averaged.
Another marketing trick is the statement that the minimal gap between homogenizer rotor and stator (even ca. 0,2 mm) enables to achieve more stable product and makes possible to produce nano-emulsion. But this what we achieve for sure, is the temperature rise on the homogenizer teeth, which can lead to product crystallization of some ingredient types and significant noise increase.
Some of the process machine manufacturers used to call homogenizer an element made of propeller and toothed stator. But such part can be only used in auxiliary mixers – not in main process mixers, because it does not guarantee 100% of repeatability. Properly designed homogenizer should ensure achieving of stable emulsion at tip speed about 30 m/s, and if necessary – even higher. The best solution is four-row tooth-shaped homogenizer, enabling to process stable, multi-phase emulsion.
Very important design elements of homogenizer are the numbers which describe phase shift between rotor-stator, and not only the gap between them. Phase shifts of rotor-stator have important influence on the homogenizer work, because if these are not properly determined, can lead to cavitation, even at proper amount of product inside the vessel.
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Taking the above mentioned contents, the technologist should be careful when listening to the suppliers assurance that only their machines are the best. He should keep in mind the fact, that many of the manufacturers still apply old and technically obsolete solutions and they fall behind modern requirements. Therefore, before making any decision regarding the proper selection of the process machine, technologist should take into consideration only these constructions, which ensure achieving of the product in accordance with assumptions. Then he will be sure that the final product will be high quality and repeatable.