Wet granulation in laboratory scale high shear mixers: Effect of binder properties

Abstract

a b s t r a c t Keywords:High shear mixer granulator Torque curves Work of adhesion Viscosity Scale-up The effect of binder properties on torque curves, granule growth kinetics, wet mass consistency and dry granule strength has been investigated in this study. Granulation runs have been performed on a fine cohesive microcrystalline cellulose powder (Avicel 105, d 50 = 20 μm) in two types of laboratory high shear mixers: a MiPro high shear mixer using a 1.9 L bowl and a 6 L Diosna high shear mixer. Binders used included ultra-pure water and solutions of varying concentrations of PVP and HPMC allowing us to cover different values for parameters like viscosity and work of adhesion. Torque curves recorded during granulation are found to allow good control of the process. Optimum liquid requirement for granulation has been found to vary with binder type and decrease with increasing viscosity while granule growth kinetics has been found to be to be related to the work of adhesion for low viscosity binders. Granule strength has been evaluated for wet granules by the means of wet mass consistency measurements on a mixer torque rheometer and for dried granules by means of uniaxial compression tests on a Texture Analyser mechanical testing machine. For low viscosity binders both wet mass consistency and dry granule strength have been found to depend on the work of adhesion. For high viscosity binders higher wet mass consistencies but lower dry granule strengths have been observed. Granulating on the larger 6 L scale has shown that constant impeller tip speed offers good agreement in terms of mean granule size however granule size distribution seems to be scale dependant.

To Evaluate the Effect of Solvents and Different Relative Humidity Conditions on Thermal and Rheological Properties of Microcrystalline Cellulose 101 Using METHOCEL™ E15LV as a Binder

“…Wet granulation is defined as the process of mixing the drug and the filler powders together, and subsequently, wetting them by a binder solution to obtain agglomerates such that the individual particles can still be differentiated (2). The type and the concentration of the binder solution used plays a critical role in the wet granulation end point determination (3,4) and also on the various physical attributes of the tablets (5,6) such as hardness, friability (7), dissolution time (8), disintegration time (9), compressibility, and the content uniformity of the tablets (10).…”

Predictive modelling of the granulation process using a systems-engineering approach

“…The impeller shape is considered as an input variable in addition to three other variables, as listed in Table 1, while the speed of the vessel is kept constant at 170 rpm. Although, there are many parameters that affect the granulation process, the aforementioned ones are the most crucial for the high shear granulation (HSG) process using specific materials [18]. The levels of each variable have been defined by conducting a set of trial experiments.…”

Upgrading wet granulation monitoring from hand squeeze test to mixing torque rheometry

“…MTR curves were used to study the influence of binder characteristics during wet granulation inside the high shear mixer (Chitu et al, 2011). Binders used were ultra-pure water and solutions of varying concentrations of PVP and HPMC.…”