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Article / Jun 20, 2025

Material-sparing method development for liquid-to-solid ratio determination for wet granulation process development

Authors:
  • Catarina Luz
  • Ricardo Sousa
  • Joao Pinto
  • Slavomira Doktorovova
Source:
International Journal of Pharmaceutics, 20 August 2025

Abstract
The liquid-to-solid (L/S) ratio is a key process parameter in wet granulation processes, which ensures that the final granules meet the desired quality attributes. Mixer torque rheometer (MTR) is an established instrument to determine this parameter by measuring torque changes as a function of liquid content. Therefore, this study aimed to assess whether IKA Magic Plant and Freeman FT4 powder rheometer could serve as reliable alternatives to the MTR for developing a material sparing method for L/S ratio determination. Three different formulations, each containing the same excipients in different ratios and water as granulation liquid were tested. Torque profiles from the IKA equipment and the “Total Energy” data from the FT4 equipment were compared with the MTR torque data. Both IKA and FT4 demonstrated good correlations with the MTR in identifying the ideal L/S ratio for high-shear wet granulation (HSWG) processes. However, these conclusions are based on literature data. Furthermore, the L/S ratios registered for twin-screw wet granulation (TSWG) processes were only similar between the MTR and the FT4. Consequently, IKA and FT4 can be regarded as valid alternatives to MTR for determining L/S ratios in HSWG processes, whereas FT4 is the only alternative for MTR when determining L/S ratios for TSWG processes. Consequently, FT4 rheometer emerged as the most reliable tool for predicting the optimum L/S ratio in both HSWG and TSWG with small material samples (4 g). Despite requiring more material, IKA is a proven production-scale system with semi-continuous capabilities, reducing the need for larger equipment.

Read the full article on ScienceDirect.com