There has been strong and increased interest in twin-screw melt granulation (TSMG) for solid oral dosage forms. TSMG relies on the dispersive and distributive mixing at the kneading zone for granule formation and growth. Therefore, proper design of kneading elements plays a predominating role in the success of TSMG.
Despite extensive research conducted on the impact of screw geometry in melt compounding, there has been limited literature for TSMG in pharmaceutical applications. Disc width for the kneading elements used in TSMG was 2 mm, contrary to the standard 5 mm used in other melt compounding processes. Considering that overflight clearance (OC) and disk width (DW) are the two key geometrical parameters that define the mixing dynamics when the formulation blend passing through the kneading elements, the main focus of our research is to elucidate the impact of varying OC and DW on the granule properties during TSMG.
We found that the new elements we designed did reduce the peak shear at kneading zone. However, a higher barrel temperature and degree of fill (DoF) are required to compensate for that change in order to attain similar granule attributes. Our study showed the higher DoF was achieved through a combination of modified screw configuration with pre-densified powders that allowed the kneading and processing to occur at a lower screw speed. On the other hand, process optimization was explored as an approach to minimize the impact of higher barrel temperature to drug stability. A thermally unstable drug, gabapentin, was utilized as a model for this process optimization study. Using the new kneading elements, compressible granules (Tensile strength > 2 MPa) with low % GABA-L content were manufactured successfully despite increasing OC to 0.4 mm. Granules obtained were stable at 40 C and ambient humidity up to 6 months, indicating gabapentin was stable (% GABA-L ≪0.4 %) despite a high barrel temperature of 120 C. In conclusion, the overflight clearance (OC) and disk width can be optimized to successfully melt-granulate even the thermally non-stable drugs.