Daniel Nesgesa, Thomas Birrb, Markus Thommesa and Jens Bartscha
a Laboratory of Solids Process Engineering, Department of Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, Germany
b ENTEX Rust & Mitschke GmbH, 44805 Bochum, Germany
* Correspondence: jens.bartsch@tu-dortmund.de; Tel.: +49-231-755-3210
Introduction
The modification of bulk materials in terms of flowability is required for various methods of pharmaceutical technology, e.g. tableting and encapsulation. Granulation is a central unit operation for this purpose [1] by adjusting the particle size.
A promising alternative continuous method in this context is the use of a planetary roller granulator. The unique process concept involving planetary spindles orbiting a temperature controlled central spindle within a temperature controlled roller cylinder (Figure 1) leads to an enhanced ratio of heated surface to free process volume. The material transition patterns between the different spindles support material mixing and thereby particle-particle contacts, which is essential for granulation [2]. Moreover, the shear stress applied by the rotating spindles is a limiting factor regarding the particle size due to breakage and attrition effects.
Figure 1: Radial cross-section of planetary roller granulator. Roller cylinder, planetary and central spindle have a 45° helical toothing. Circulation direction of central and free-flowing planetary spindles is concurrent and self-rotation of planetary spindles is counter-current.
The application of planetary roller granulator for melt granulation matches several recent trends and requirements of the pharmaceutical technology. This includes the establishment of continuous methods [3, 4]. These offer significant advantages related to process control in terms of processing in a dynamic steady state. This leads to an enhanced product quality and cost efficiency as well as scalability [5]. Moreover, the handling of temperature sensitive materials requires an enhanced control level with respect to the thermal and mechanical energy input. Here, the enhanced ratio of heated surface to processed volume in addition to the individual temperature control concept is especially valuable. Finally, the enhanced level of process control in planetary roller processing is a fundamental basis for the automation of production processes. Therefore, the aim of this study is to evaluate planetary roller melt granulation (PRMG) as alternative continuous method for pharmaceutical technology. Therefore, the impact of directly adjustable process parameters on the energy input mechanisms related to material heating and the resulting product temperature is investigated as well as on the granulation performance represented by the derived product particle size distribution.
Materials and Methods
The experimental study was carried out on a lab scale granulator (PWE 30, Entex Rust & Mitschke GmbH, Bochum, Germany), which is driven by a motor. The rotation speed during the experimental investigations was varied on four equidistant levels in a range from 50 to 200 rpm. The processing section consisted of a single module, which was configured with five standard planetary spindles, and an open orifice at the end for a pressure-free product release. The model formulation was fixed at a composition of 90 wt% model compound (Lactos 310, Foremost Farms USA, Baraboo, USA) and 10 wt% meltable binder (Klucel EXF Pharm, Ashland Inc., Covington, USA). The premix was dosed with a gravimetric feeder (DDW-M-DSR 28-5, Brabender GmbH & Co. KG, Duisburg, Germany) and the feed rate was varied during the experiments in a range from 0.35 to 1.4 kg h-1 at four different levels. Thermal process control was realized by external oil-operated temperature control units (STO 1-24-60-D2, Single Group GmbH, Hochdorf, Germany) including a by-pass system. The set temperatures for both heat systems were fixed for all conducted experiments at 140 °C. While the product temperature was determined with an IR-camera (Test 875, Testo SE & Co. KGaA, Titisee-Neustadt, Deutschland), dynamic picture analysis (Sympatec GmbH, Clausthal-Zellerfeld, Germany) was utilized to characterize the product particle size.
Results and Discussion
Energy input during processing
During PRMG, the energy input per processed material mass refers to the specific mechanical energy input or specific thermal energy input. While in the first case this is related to material shearing by the rotating spindles, the second case is related to heat conduction over the heated surface of the roller cylinder or central spindle.
Both energy inputs decrease for an increase of the feed rate at constant rotation speed. This is caused by the general process concept and the rotation pattern of the spindles. The processed material is transferred between the central and planetary spindles. Therefore, the contact area between the three main components is filled first, while the free spaces in between are filled up at higher feed rates. Here, the energy input for the mechanical as well as the thermal energy input mechanism is less effective. Further, the residence time is shortened for an increase of the feed rate, which limits the time for energy transfer into the material. At the same time, the material distribution within the radial cross-section with respect to the general fill level of the machine is rather constant at a specific feed rate level. Therefore, an increase of the rotation speed results in an elevated mechanical energy input due to higher shear forces. Since the thermal energy input is barely affected by a variation of the rotation speed, this implies a sufficient kinetic of the heat conduction even at higher material substitution rate at the surfaces. The parameter variation also reduces the residence time, which limits the time for energy transfer into the material.
Figure 2: Specific mechanical and thermal energy as a function of the applied feed rate represented by the colors, while symbols encode for the rotation speed.
Product temperature
During PRMG, both energy input mechanisms occur simultaneously and define the overall material heating. Hereby, the temperature increase related to the thermal energy input is naturally limited by the set temperature. A temperature increase beyond this limit must be related to the mechanical energy input. Consequently, the product temperature results from the ratio of the energy input mechanisms. The results of the experimental investigations are displayed in Figure 2 for the product temperature normalized by the set temperature.
Overall, the results highlight the direct correlation between product temperature and energy ratio. This is valid for the investigated heating system and range of the energy input ratio. For most of the investigated process parameter sets, the thermal energy input is dominant (energy input ratio < 1). Here the overall product temperature is closer to the set temperature in comparison to a process state symbolizing a dominant mechanical energy input (energy input ratio >1). However, in both cases, a decrease of the energy input ratio leads to a decrease of the normalized product temperature. This is due to an increased energy input efficiency of conduction over the heated surface. Here, the corresponding kinetic is sufficient in terms of material softening or plasticization required for the transport and granulation
mechanism during PRMG. Therefore, the demand for mechanical energy input decreases.
Figure 3: Normalized product temperature in dependence of the energy input ratio as specific mechanical to thermal energy input. Applied feed rate represented by the colors, while symbols encode for the rotation speed.
Product particle size distribution
The impact of the feed rate and rotation speed in PRMG on the product quality represented by the cumulative size distribution are highlighted in Figure 4.
In general, by increasing the rotation speed the applied shear stress is enhanced, which promotes the mechanism of attrition and breakage [2] and shifts the size distribution to smaller values in comparison to the model compound (circular symbols). In contrast, a higher load due to a feed rate increase for a constant screw speed promotes particle-particle interaction. Therefore, the agglomeration mechanism [2] is enhanced and the median value of the size distribution is shifted to larger values. The impact of this effect increases for higher rotation speeds. However, for the highest screw speed there appears to be an optimal feed rate in between with respect to particle size enlargement. This is due to the balance of the different granulation mechanisms.
Figure 4: Volumetric particle size distribution of granular product. Applied feed rate represented by the colors, while symbols encode for the rotation speed. Circular symbols highlight model compound before granulation.
Conclusion
Melt granulation with a planetary roller granulator is a promising alternative for pharmaceutical technology, since the unique process concepts enables an enhanced level of process control. Direct process parameters are suitable to adjust the energy input mechanisms, which leads to an enhanced level of process control. Moreover, the variation of the direct process parameters manipulates the balance of the granulation mechanisms during processing and thereby affect the particle size distribution of the granular product. Finally, this new method matches the demand for continuous manufacturing methods
References
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