Rapid assessment of sedimentation stability in dispersions using near-infrared transmission measurements during centrifugation and oscillatory rheology
Martin Kuentz*, Dieter Rothlisberger
F. Hoffmann-La Roche Ltd., Basel, Switzerland
European Journal of Pharmaceutics and Biopharmaceutics 56 (2003) 355–361, https://doi.org/10.1016/S0939-6411(03)00108-5
(https://www.sciencedirect.com/science/article/abs/pii/S0939641103001085?via%3Dihub)
Research Topic:
The authors used the LUMiFuge to study the sedimentation of bentonite and xanthan gum dispersions. They also compared the results obtained by the LUMiFuge to rotational and oscillatory rheology. Rheological parameters compared well with the LUMiFuge results. The paper concludes that the LUMiFuge can be used to screen formulations for long-term stability and shelf-life tests and is a valued time-saving tool.
Keywords: Dispersion stability; Sedimentation; LUMiFuge; Rheology; Bentonite; Xanthan gum; Long term stability; Shelf-life
Paper Highlights:
“The critical parameters in early formulation development are time, resources, and availability of drug substances. It is therefore vital to enter as few formulations as possible into conventional long-term stability tests at different temperatures. Such formulations should be pre-selectable for stability throughout the anticipated shelf-life. This can only be achieved by rapid and effective physical screening.”
This publication compares LUMiFuge sedimentation stability and yield point determination with those obtained using a traditional rheometer. The authors used bentonite (Veegum) and xanthan gum (Vanzaan) based formulation.
Traditional views hold that the easiest and best way towards phase separation stability is to increase the viscosity of the formulation by adding more and more thickeners. While this is correct sometimes, it also often fails especially when working with hydrocolloids resulting in poor formulations that either fail or are overdosed with thickeners.
Figures 2 and 3 are beautiful graphs that illustrate this important and often seen phenomenon. While viscosity does continuously increase with the increasing concentration of Veegum and Xanthan gum, the phase separation undergoes a stability minima at intermediate concentrations. Meaning there is a range of concentration thickeners where the phase separation stability decreases despite increasing viscosity. For laboratories and formulators that only rely on rheological measurements to predict and measure shelf-life, this may lead to incorrect results.
The second part of the paper discusses the usage of yield points to induce phase separation stability. The authors performed oscillatory rheology measurement via the storage moduli to measure yield points and compared them with the yield points obtained using the LUMiFuge method. They found that the LUMiFuge and rheology-based yield points largely overlapped. The LUMiFuge slightly overestimated the yield point numbers compared to that of the rheometer. Based on my experience, this is likely due to the authors using the clarification rate analysis module that is part of the LUMiFuge software package and not the Sedimentation Front Tracking software module.
The findings are an excellent example of the difference between a direct and indirect stability measurement. Rheological measurements are extremely important and necessary for a variety of product applications (flow, feel, etc). However, rheology is an indirect measurement with regard to product stability. The LUMiFuge measures stability directly and thus correctly. It is a first principle method of analysis.
