As a result of changing philosophies towards continuous developing, new equipment has been introduced into pharmaceutical production facilities. The twin-screw extruder can be an example of such equipment for make use of in wet granulation. The authors analyze advancements in wet granulation using a twin-screw extruder; construct the presssing issues with wetting found in this machine; and introduce a novel technique, foam granulation, that uses the twin-screw extruder to fully satisfy the unique requirements of granulation.
The twin-screw extruder provides highly consistent granulates because of its continuous operation and closely confined flow path, which requires that all particles experience a similar shear history. The intensive blending of the twin-screw extruder allows lower optimal liquid concentration for granulation while providing denser granules for both placebo formulations and highly dosed drugs compared to a high-shear batch mixer. As a total result, drying and milling operations could be reduced with use of this machinery in solid oral-dosage production significantly.
The binding liquid in wet granulation has a profound influence on product granule properties and affects the friction between conveyed powders and the barrel wall in the extruder, which affects power consumption and the exiting temperature of granules. There are crucial concerns to be solved in regards to introducing liquids into this type of machinery to acquire rapid and uniform wetting of excipients so the process exhibits stability in operation, boundaries become promptly lubricated to lessen equipment wear and granule heating, and top quality granulates are obtained.
A basic variant of extruder used for granulation is the fully intermeshing, co-rotating twin-screw extruder. Differences between suppliers are largely using the available internal level of the machine in addition to the screw diameter, both of which can substantially affect granulate homes in both granule size and intragranular porosity. The machine is highly modular, rendering it a flexible program for continuous manufacturing of different products during its lifetime of system to a company. The intermeshing region between your two screws creates a self-wiping actions that minimizes material accumulation within the machine but also provides a complex flow route for powders to mix and consolidate. For wet granulation, the die end of the extruder is generally open to collect granules without unnecessary consolidation.
Wet granulation inside the co-rotating twin-screw extruder is a starve-fed method, and therefore the available internal volume of the machine is under no circumstances completely filled up with material during operation. This modus operandi is essential to extrusion because it minimizes dissipative heating build-up in conveyed medication formulations as it limitations compression against the barrel wall, it decouples the parameters of output screw and rate speed to provide formulators even more control over their procedure, and it more readily enables the downstream addition of substances because the system is not pressurized aside from small mixing regions. The zones of the screws that are starved knowledge dominant drag flow, in which powders are pushed by the rotating flights of conveying-type elements downstream. These screw elements have already been identified to contribute little to granule growth. In fact, screw designs using only conveying elements show inadequate distribution of the binding liquid within exiting solids. It really is rare, however, that a screw design is completely comprised of conveying components or that the entire amount of the machine is ever totally starved. Significant granule expansion necessitates the inclusion of pressure-driven mixing zones, which are necessarily fully filled as powders will be squeezed through these sections. Kneading blocks and comb elements are types of mixers popular in sparing numbers across the screw length to create granule growth alongside minor attrition. Keeping these mixing elements closer to the final end of the extruder reduces attrition.
twin screw extrusion
Powder flow charge is among the most crucial parameters influencing the level of granule progress, with higher outputs producing larger granules. The result is induced by the higher volumes of powder that build up in front of pressure-powered mixing zones as move rate increases, producing much larger axial compressive forces on the particles present. In fact, it's been shown that the dispersion of binder within poorly wetted mass can be increased for granulation if the screw design and flow charge are adjusted to supply ideal compressive forces. The impact of flow amount on granule growth, however, is not often seen in smaller extruders or highly starved processes. Increasing screw speed has less effect on granule size but generally escalates the number of chopping events provided by mixing zones to lessen the occurrence of oversized particles. For a fixed flow rate, increasing the screw speed will certainly reduce the quantity of powder that fills the conveying screw elements, leading to lower power consumption by the process.
Among the published research for wet granulation, a crucial point that's rarely mentioned, yet well known to the pharmaceutical industry, is the difficulty of wetting a formulation in an extruder uniformly. The problem arises because of the earlier mentioned carefully confined space inside the extruder, which outcomes in the liquid injection port staying in immediate proximity to the powder flow. This confinement prevents atomization of the binder formula into micro-sized droplets prior to contacting the powder solids, as is done in high-shear batch mixers. Due to this fact, regions of the powder become oversaturated while some remain dry virtually. This matter was highlighted in the industrial-oriented document by Shah, who reported method surging, though electric motor overload events are as well common. Shah demonstrated several approaches linked to screw design and the sequential addition of more compact liquid quantities into the process as means to minimize surging occurrences. Such improvements greatly raise the complexity of operating the extruder and do not eliminate the root trigger of the problem. Alternatively, a new solution called foam granulation uses the initial behavior of aqueous foam to cause rapid spreading of the binding liquid over a large section of the powder during wetting.