A continuous manufacturing concept for a pharmaceutical oral suspension

Abstract

The aim of this study was to investigate the applicability of an innovative continuous manufacturing system for semi-solid and liquid pharmaceutical formulations. A commercially available pharmaceutical oral suspension was selected as model formulation. Premixes of the raw materials were dosed via peristaltic pumps to the mixing compartment, which consists of two consecutive mixing units. An experimental design was used to study the influence of several process parameters (throughput, mixing speed in mixing unit 1 and mixing speed in mixing unit 2) on the quality attributes of the oral suspension. The pH, density, active pharmaceutical ingredient (API) concentration, sedimentation after 30 days (expressed by the sedimentation volume) and rheological characteristic (yield stress) of the suspension were determined. No significant influence of the process parameters on the pH, density and API concentration was observed. The throughput and mixing speed in mixing unit 1 had a significant impact on both the sedimentation volume and yield stress, and were therefore critical to acquire physical stable suspensions. Furthermore, the yield stress measured one day after production was predictive for the occurrence of sedimentation in the suspensions after 30 days. When selecting the optimal process settings, the continuously manufactured suspension had a similar product quality as the original batch-processed suspension and even possessed a higher yield stress. This study demonstrated that the investigated innovative continuous manufacturing technology is suitable for the manufacturing of a commercially available pharmaceutical suspension and that the product quality can be optimized by adjusting the process parameters.