The twin-screw wet granulation (TSWG) is a manufacturing process showing versatility, straightforward scale-up and the possibility of integration in a continuous manufacturing line. The presentation will provide an overview of the TSWG and its applications in pharmaceutical development area. Then, it will focus on a case-study in which, a leading formulation containing a soluble drug (namely niacin), was used in a 2(5-1) fractional factorial design of experiment (DoE). This screening study was conducted to assess the influence of five factors (screw design, screw speed, liquid/solid ratio, powder feed rate and milling screen type) on the process outcomes (e.g. torque) and the quality attributes of granules (e.g. particle size distribution (PSD), density and flowability) and tablets (e.g. tensile strength, friability and disintegration time).
All statistical models were significant with p < 0.05 and a high level of goodness of fit (R2) was observed for the majority of responses. The TSWG was a viable approach to manufacture granules with suitable friability and flowability. The selection of the milling sieve was critical for the attributes of the granules: the screen type influenced the granule PSD, friability and density also as an interaction with other factors thus, the importance of the granulation downstream. The tablets showed adequate tensile strength and friability. With low screw speed and high L/S ratio (as a main effects) harder tablets were obtained. Faster disintegration was achieved with a low-shear screw configuration and high L/S ratio.
In conclusion, a screening design was implemented as a “model view” to evaluate the impact of key TSWG process parameters towards the properties of granules and tablets.
Learning Objectives:
Overview of the twin-screw wet granulation (TSWG) technology and its applications in the pharmaceutical development
Brief discussion of the granulation mechanisms through TSWG and potential effects of processing paramenters
A case study: evaluation of process factors in a TSWG influencing process responses as well as the critical properties of granules and tablets