Influence of twin-screw wet granulation process parameters on granule quality of a high-dose hydrophobic drug

NAZARETH E. CESCHAN; M. CECILIA BALBI; RAVAZZOLI, PABLO; GERMÁN DRAZER ; FERNANDO MUZZIO; GERARDO CALLEGARI

North Bethesda

Congreso; IFPAC; 2023

Continuous manufacturing in pharmaceutical industry has received significant attention due to its advantages over batch manufacturing. While a batch process involves multiple steps taking place sequentially, continuous processes avoid hold times and intermediate products obtainment. Manufacturing of solid dosage forms may require a granulation step to improve flowability and tabletability of excipients and drugs. Twin-screw granulators are well-suited for continuous processes. Particularly, wet granulation of high-dose hydrophobic drugs is challenging since these characteristics greatly affect the extent of wetting of the powder, which may lead to non-uniform distribution of the drug in the final dose. In this work, the influence of process parameters on granules characteristics produced using a formulation with the high-dose hydrophobic drug ibuprofen was statistically analyzed. A full factorial design was conducted. Screw speed, throughput, and L/S ratio were selected as factors. Granule porosity, granulation yield (fraction with a granule size between 125-2000μm), content uniformity, tablet tensile strength, disintegration and dissolution was evaluated. Additionally, wettability of Ibuprofen, excipient, and full formulation was studied. Drug content uniformity was confirmed for all runs. Granule properties were highly affected by L/S ratio, however it was demonstrated that good quality granules were obtained at acceptable and relatively low L/S, an important factor to minimize the time to dry the granules continuously.