Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants
The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.
Download the full article here: Immediate-Release Formulations Produced via Twin-Screw Melt Granulation
Article information: Steffens, K.E., Wagner, K.G. Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants. AAPS PharmSciTech 22, 183 (2021). https://doi.org/10.1208/s12249-021-02056-0
More on CMC and Croscarmellose Sodium
Material
PCM (d50 = 7.6 μm (laser diffraction, Helos KF (Sympatec GmbH, Clausthal-Zellerfeld, Germany) dry-dispersed with a pressure of 1 bar, focal length 200 mm, calculated according to Frauenhofer theory, software Windox 4.2.1.) was obtained from Mallinckrodt Pharmaceuticals (Staines-Upon-Thames, UK). Due to its low melting point (55–60°C), the binder PEG 6000 was used and purchased from Carl Roth (Karlsruhe, Germany). Granulation of PCM required the addition of 1% (w/w) colloidal silicium dioxide (AEROSIL® 200) which was a gift from Evonik (Evonik Resource Efficiency GmbH, Hanau-Wolfgang, Germany). Sodium starch glycolate (Vivastar® P) and croscarmellose sodium (Vivasol® GF) were donated by JRS (J. RETTENMAIER & SÖHNE GmbH + Co KG, Rosenberg, Germany). Additionally, crospovidone (Kollidon® CL-F) was tested as a disintegrant, which was a gift from BASF (BASF SE, Ludwigshafen, Germany). Magnesium stearate (Ligamed® MF-2-V) was donated by Peter Greven (Peter Greven GmbH & Co. KG, Bad Münstereifel, Germany).
Conclusion
The current study showed that especially extra-granular addition of superdisintegrant revealed fast disintegrating tablets with subsequently short Q80%. At the same time, the benefits of tablets from TSMG like excellent tensile strength and friability could be remained even in combination with a high drug load (> 80% (w/w)). The rank order in efficiency for extra-granular addition was CPV > CCS > SSG. For SSG, higher concentrations of >6% (w/w) were needed, whereas already 4% (w/w) achieved acceptable results for CPV and CCS. Intra-granular addition showed mainly negative effects on the disintegration performance. This effect was very pronounced, when CPV was added into the granulation process and to a lesser extent for CCS. In contrast, SSGs disintegration efficiency was unaffected by the granulation process. The results are of fundamental importance, when using TSMG in a continuous processing line and additional mixing steps after granulation should be avoided.