Comparing integrated continuous process “LaVortex®” and conventional batch processes for the pharmaceutical manufacturing of acetaminophen oral dosage formulations: Challenges and pharmaceutical properties of the granular and tableted products

Abstract

LaVortex® was developed as a novel free-flow continuous granulation/drying (CGD) system. In this study, we compared the advantages and disadvantages of granules prepared by continuous and batchwise manufacturing systems. Granules containing 30 % acetaminophen were manufactured under various operating conditions using CGD system, with comparison granules manufactured using conventional batch systems that involve a combination of fluid bed granulation (FG), agitation granulation (AG), continuous drying, fluid bed drying, and/or shelf drying, after which the pharmaceutical properties of each type of manufactured granule were evaluated. Cumulative particle-size distributions were determined by sieving, powder flowabilities were determined by angle of repose measurements, and scanning electron microscopy was employed to examine granule morphologies. The CGD system produced fine-to-large spherical or ellipsoidal granules that exhibited excellent powder fluidities and tabletabilities that are almost identical to those of AG granules. Moreover, the CGD granules exhibited better powder flowability than the FG granules. The addition of water promoted CGD-granule growth and improved significantly powder flowability, and did a little in tabletability. Small spherical granules with good fluidity suitable for fine-particle-coating core materials, or large granules with excellent fluidity and tabletability, were prepared by adjusting the values of the elemental parameters of the CGD process.