Impact of Formulation Properties and Process Parameters on the Dispensing and Depositioning of Drug Nanosuspensions Using Micro-Valve Technology

Flexible manufacturing processes with continuously adjustable dose strengths are considered particularly innovative and interesting for applications in personalized medicine, continuous manufacturing, or early drug development. A piezo-actuated micro-valve has been investigated for the dispensing and depositioning of drug nanosuspensions onto substrates to facilitate the manufacturing of solid oral dosage forms. The investigated micro-valve has been characterized regarding dispensing behavior, mass flow, accuracy, and robustness. The amount of dispensed drug compound during 1 dispensing event could be continuously adjusted from a few micrograms to several milligrams with high accuracy. Fluid properties, dispensing parameters of the micro-valve, and the resulting steady state mass flow could be correlated adequately for low-viscous drug nanosuspensions. High-speed imaging was used to investigate the dispensing behavior of the micro-valve regarding the evolution of the dispensed drug nanosuspension after ejection from the nozzle and the behavior during impact on flat and dry solid substrates. The experimentally determined breakup length of the dispensed liquid jet could be correlated with a semiempirical equation. From image sequences of the jet impact, We-Re phase diagrams could be established, providing a profound understanding and systematic guidance for the controlled depositioning of the entire dispensed drug nanosuspension onto the substrate. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.