title: New Approach and Practical Modelling of Bead Milling Process for the Manufacturing of Nanocrystalline Suspensions.
abstract: Stirred media milling is the main technology for producing colloidal nanocrystalline suspensions. A number of studies have been reported on the effect of different operating parameters for lab, pilot, and industrial scales. However, typical milling tool box that can be used to support candidate from selection up to phase III clinical supplies can involve different mill configurations. This article describes a parametric study and milling kinetic modelling of the different mills. The impact of active pharmaceutical ingredient (API) type and process parameters on milling kinetics was determined. The milling kinetics were modeled using an empirical model which allows for predicting and simulation of milling kinetics of stirred annular and pin mills. The proposed model was found to accurately fit milling kinetics whatever the API considered, technology employed, and the process parameters used for milling. Moreover, the model was found to be able to ensure the process transfer from one mill to another.
authors.affiliation: Sanofi R&D, 1, Impasse des ateliers, Vitry sur Seine 94403, France. Electronic address: mostafa.nakach@sanofi.com.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Nakach
authors.affiliation: Sanofi R&D, 1, Impasse des ateliers, Vitry sur Seine 94403, France.
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Authelin
authors.affiliation: Sanofi R&D, 1, Impasse des ateliers, Vitry sur Seine 94403, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Agut
mesh_terms: D000465:Algorithms; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D013535:Suspensions
keywords: Avrami equation; modelling; nanocrystalline suspension; stirred bead milling