A new approach to produce drug nanosuspensions CO2-assisted effervescence to produce drug nanosuspensions

摘要

The exploration of a simple and robust approach to produce nanosuspensions is a meaningful attempt for clinical translation. CO2-assisted effervescence was firstly developed to prepare nanosuspensions and was found to be easy for scale-up. Drug nanosuspensions were easily obtained by adding aqueous carbonate to the pre-treated mixture of drug, stabilizer and organic acid. The burst of CO2 bubbles resulted from the acid-base reaction insert a micro gas bubble smashing and mixing effect to the formation of nanosuspensions, leading to smaller sizes and a refined size distribution. We successfully prepared nanosuspensions with twelve structurally diverse drugs. Alternatively, solid carbonate blended with the mixture, allowing for later addition of water, also facilitates the formation of amorphous nanosuspensions. We defined this approach as in situ nanoamorphization (ISN). Intensive in vitro and in vivo investigations for itraconazole and cabazitaxel nanosuspensions validate the availability for administration. (C) 2016 Elsevier B.V. All rights reserved.