title: A new and improved method for the preparation of drug nanosuspension formulations using acoustic mixing technology.
abstract: Drug discovery and development is a challenging area. During the drug optimization process, available drug compounds often have poor physicochemical and biopharmaceutical properties, making the proper in vivo evaluation of these compounds difficult. To address these challenges, drug nanoparticles of poorly soluble compounds have emerged as a promising formulation approach. Herein, we report on a new drug sparing technology utilizing low shear acoustic mixing to rapidly identify optimized nanosuspension formulations for a wide range of compounds with dramatically improved material and time efficiencies. This approach has several key advantages over typical methods of preparing nanoparticles, including miniaturization of the milling process, the ability to evaluate multiple formulation conditions in a high throughput manner, and direct translation to optimized formulation scale-up for in vivo studies. Furthermore, there are additional benefits obtained with this new approach resulting in nanosuspension formulations with significant stability and physical property enhancements over those obtained using traditional media milling techniques. These advantages make this approach highly suitable for the rapid evaluation of potential drug candidates in the discovery and development space.
authors.affiliation: Merck & Co., Inc., Rahway, NJ, United States. Electronic address: dennis_leung@merck.com.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Leung
authors.affiliation: Merck & Co., Inc., Rahway, NJ, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lamberto
authors.affiliation: Merck & Co., Inc., Rahway, NJ, United States.
authors.forename: Lina
authors.initials: L
authors.lastname: Liu
authors.affiliation: Kwong Eureka Solutions, Montreal, Quebec, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kwong
authors.affiliation: Merck & Co., Inc., Rahway, NJ, United States.
authors.forename: Todd
authors.initials: T
authors.lastname: Nelson
authors.affiliation: Merck & Co., Inc., Rahway, NJ, United States.
authors.forename: Timothy
authors.initials: T
authors.lastname: Rhodes
authors.affiliation: Merck & Co., Inc., Rahway, NJ, United States.
authors.forename: Annette
authors.initials: A
authors.lastname: Bak
mesh_terms: D000162:Acoustics; D003198:Computer Simulation; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D057446:Hydrodynamics; D053758:Nanoparticles / Q000737:chemistry; D009288:Naproxen / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013535:Suspensions; D014783:Viscosity
chemical_list: D011108:Polymers; D013501:Surface-Active Agents; D013535:Suspensions; D009288:Naproxen
keywords: Formulation; High throughput technologies; Milling; Nanoparticles; Nanotechnology; Naproxen CID: 156391; Particle size