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Freeze-drying of nanoparticles Formulation, process and storage considerations
ews 58 (2006) 1688–1713 /locate/addrAdvanced Drug Delivery ReviFreeze-drying of nanoparticles: Formulation, process and storage considerations☆ Wassim Abdelwahed a, Ghania Degobert a,?, Serge Stainmesse b, Hatem Fessi a a Laboratoire dAutomatique et de Génie des Procédés (LAGEP) UMR-CNRS 5007 CPE Lyon, ISPB, Université Claude Bernard Lyon 1, 43, Boulevard du 11 Novembre 1918, 69622 Villeurbanne cedex, France b Conservatoire National des Arts Métiers-Chaire des Techniques Pharmaceutiques, 292, rue Saint Martin, 75141 Paris, Cedex 03, France Received 14 September 2006; accepted 29 September 2006 Available online 6 October 2006Abstract Freeze-drying has been considered as a good technique to improve the long-term stability of colloidal nanoparticles. The poor stability in an aqueous medium of these systems forms a real barrier against the clinical use of nanoparticles. This article reviews the state of the art of freeze-drying nanoparticles. It discusses the most important parameters that influence the success of freeze-drying of these fragile systems, and provides an overview of nanoparticles freeze-drying process and formulation strategies with a focus on the impact of formulation and process on particle stability. ? 2006 Elsevier B.V. All rights reserved.Keywords: Nanoparticles; Freeze-drying; Stability; Freezing; Cryoprotectant; Glass transition; Physical and chemical characterization; Formulation Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1689 2. Stability of nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1690 2.1. Physical stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1690 2.2. Chemical stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1691 2.2.1. Effect of polymer type . . . . . . . . . . . . . . . . . . . . . . . .
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