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.
Highlights
- Optimal liquid-to-solid ratio can be determined using only 4 g of material.
- FT4 rheometer is a viable alternative to the MTR for torque rheometry applications.
- IKA Magic Plant can assess wet mass stages despite being low-shear.
- More microcrystalline cellulose may contribute to mixing heterogeneity.
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.
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Materials
The materials considered for the preparation of the granules included Microcrystalline Cellulose (MCC, Avicel PH-101, FMC Corp, Ireland), Lactose Monohydrate (LAC, Granulac 200, Meggle GmbH, Germany) and Polyvinylpyrrolidone K30 (PVP, BASF, Germany) (Table 1). Demineralized water served as granulation liquid throughout the study.
Catarina Luz, Ricardo Sousa, João F. Pinto, Slavomira Doktorovová, Material-sparing method development for liquid-to-solid ratio determination for wet granulation process development, International Journal of Pharmaceutics, Volume 681, 2025, 125821, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125821.
Read also our introduction article on Microcrystalline Cellulose here:
