Continuous twin screw granulation: Robustness of lactose/MCC-based formulations.

Abstract

In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response behavior of four formulations containing APIs (5-10% drug load) with diverse characteristics was compared to the behavior of the corresponding placebo formulation consisting of lactose, microcrystalline cellulose (MCC) and hydroxypropylmethylcellulose (HPMC). API selection was based on extensive material characterization, combining conventional testing with in silico descriptors. For each formulation, a design of experiments was set up, evaluating the impact of liquid to solid (L/S) ratio and screw speed. Response ranges, response behavior and processability of each of the four formulations proved very similar to the placebo formulation when an appropriate center point L/S ratio was chosen. Hence, this robust placebo formulation could prove useful by decreasing drug product development time and consequently providing patients with a faster access to innovative medicine. Additionally, APIs with similar properties exhibited highly comparable response behavior at similar L/S ratios, indicating the potential use of surrogate APIs in novel drug product development.