title: Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE).
abstract: Design of experiments (DOE), a component of Quality by Design (QbD), is systematic and simultaneous evaluation of process variables to develop a product with predetermined quality attributes. This article presents a case study to understand the effects of process variables in a bead milling process used for manufacture of drug nanoparticles. Experiments were designed and results were computed according to a 3-factor, 3-level face-centered central composite design (CCD). The factors investigated were motor speed, pump speed and bead volume. Responses analyzed for evaluating these effects and interactions were milling time, particle size and process yield. Process validation batches were executed using the optimum process conditions obtained from software Design-Expert® to evaluate both the repeatability and reproducibility of bead milling technique. Milling time was optimized to <5 h to obtain the desired particle size (d90 < 400 nm). The desirability function used to optimize the response variables and observed responses were in agreement with experimental values. These results demonstrated the reliability of selected model for manufacture of drug nanoparticles with predictable quality attributes. The optimization of bead milling process variables by applying DOE resulted in considerable decrease in milling time to achieve the desired particle size. The study indicates the applicability of DOE approach to optimize critical process parameters in the manufacture of drug nanoparticles.
authors.affiliation: Department of Pharmacy, Western University of Health Sciences, Pomona , CA , USA and.
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Nekkanti
authors.forename: Ashwani
authors.initials: A
authors.lastname: Marwah
authors.forename: Raviraj
authors.initials: R
authors.lastname: Pillai
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards*; D011345:Fenofibrate / Q000138:chemical synthesis / Q000592:standards; D053758:Nanoparticles / Q000737:chemistry* / Q000592:standards*; D010316:Particle Size; D058996:Quality Improvement / Q000592:standards*
chemical_list: D011345:Fenofibrate
keywords: Bead milling; QbD; central composite design; design of experiments; process optimization