Foam Granulation part 1

Due to changing philosophies towards continuous developing, new equipment has been introduced into pharmaceutical production facilities. The twin-screw extruder is an exemplory case of such equipment for make use of in wet granulation. The authors critique developments in wet granulation using a twin-screw extruder; lay out the issues with wetting in this machine; and introduce a novel approach, foam granulation, that uses the twin-screw extruder to totally satisfy the unique needs of granulation.

plastic sheet extruder

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 mixing of the twin-screw extruder allows lower ideal liquid concentration for granulation while delivering denser granules for both placebo formulations and highly dosed drugs in comparison to a high-shear batch mixer. As a total result, drying and milling operations may be significantly reduced with use of this machinery in solid oral-dosage production.

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 inside the extruder, which affects power consumption and the exiting temperature of granules. You can find crucial concerns to be solved in regards to introducing liquids into this sort of machinery to acquire rapid and uniform wetting of excipients so that the process exhibits stability in operation, boundaries become lubricated to lessen equipment wear and granule heating immediately, and high quality granulates are obtained.

A basic variant of extruder useful for granulation may be the fully intermeshing, co-rotating twin-screw extruder. Differences between vendors are largely using the available internal volume of the machine plus the screw diameter, both which can drastically affect granulate real estate in both granule size and intragranular porosity. The machine is modular highly, making it a flexible program for constant manufacturing of different products during its lifetime of program to a company. The intermeshing location between the two screws creates a self-wiping actions that minimizes materials accumulation within the machine but also offers 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 extreme consolidation.

Wet granulation inside the co-rotating twin-screw extruder is a starve-fed process, and therefore the available internal volume of the machine is hardly ever completely filled with material during operation. This modus operandi is essential to extrusion since it minimizes dissipative high temperature build-up in conveyed drug formulations as it limits compression against the barrel wall, it decouples the parameters of output pace and screw speed to provide formulators more control over their procedure, and it more easily permits the downstream addition of substances because the system isn't pressurized except for small mixing regions. The zones of the screws which are starved encounter dominant drag flow, where powders happen to be pushed by the rotating flights of conveying-type elements downstream. These screw elements have been located to contribute minor to granule growth. Actually, screw designs only using conveying elements show very poor distribution of the binding liquid within exiting solids. It really is rare, however, that a screw design is totally comprised of conveying factors or that the entire length of the machine is ever totally starved. Significant granule progress necessitates the inclusion of pressure-driven mixing zones, which are necessarily completely filled as powders happen to be squeezed through these sections. Kneading blocks and comb elements are types of mixers commonly used in sparing numbers across the screw length to create granule growth alongside minor attrition. Keeping these mixing elements nearer to the finish of the extruder reduces attrition.

Powder flow charge is among the most crucial parameters influencing the level of granule development, with larger outputs producing bigger granules. The result is caused by the bigger volumes of powder that build up before pressure-motivated mixing zones as movement rate increases, producing greater axial compressive forces on the particles present. In fact, it has been shown that the dispersion of binder within poorly wetted mass could be improved for granulation if the screw design and flow cost are adjusted to provide appropriate compressive forces. The affect of flow price on granule growth, on the other hand, is not seen in smaller extruders or highly starved operations often. Increasing screw speed has less effect on granule size but generally increases the amount of chopping events provided by mixing zones to lessen the occurrence of oversized contaminants. For a set flow rate, increasing the screw speed shall decrease the volume of powder that fills the conveying screw elements, resulting in lower power intake by the process.

Among the published studies for wet granulation, an essential point that's mentioned, yet recognized to the pharmaceutical industry widely, is the difficulty of wetting a formulation in an extruder uniformly. The problem arises as a result of earlier mentioned carefully confined space inside the extruder, which effects in the liquid injection port being in immediate proximity to the powder flow. This confinement prevents atomization of the binder remedy into micro-sized droplets ahead of contacting the powder solids, as is done in high-shear batch mixers. Due to this fact, parts of the powder become oversaturated while others remain dry virtually. This presssing issue was highlighted in the industrial-oriented article by Shah, who reported procedure surging, though electric motor overload events are common also. Shah demonstrated several tactics linked to screw design and the sequential addition of smaller liquid quantities into the process as means to minimize surging occurrences. Such adjustments greatly raise the complexity of operating the extruder and do not eliminate the root reason of the issue. Alternatively, a new solution called foam granulation uses the unique behavior of aqueous foam to cause quick spreading of the binding liquid over a large area of the powder during wetting.

Write a comment

Comments: 0