Nanosizing — Oral formulation development and biopharmaceutical evaluation ☆ Filippos Kesisoglou, Santipharp Panmai, Yunhui Wu ⁎ Department of Pharmaceutical Research, Merck & Co., Inc., West Point, PA, USA Received 21 March 2007; accepted 10 May 2007 Available online 25 May 2007 Abstract Poor aqueous solubility represents a major hurdle in achieving adequate oral bioavailability for a large percentage of drug compounds in drug development nowadays. Nanosizing refers to the reduction of the active pharmaceutical ingredient (API) particle size down to the sub-micron range, with the final particle size typically being 100–200 nm. The reduction of particle size leads to a significant increase in the dissolution rate of the API, which in turn can lead to substantial increases in bioavailability. This review describes the principles behind nanosizing, the production and characterization of nanoformulations as well as the current experience with utilization of such formulations in vivo. © 2007 Elsevier B.V. All rights reserved. Keywords: Nanosizing; Nanoparticle; Nanosuspension; Bioavailability enhancement; Dissolution; Formulation Contents 1. Introduction ............................................................. 632 2. Increasing dissolution rate through nanosization — theoretical aspects ............................... 632 3. Formulation development of nanoformulations ........................................... 633 3.1. Selection of excipients .................................................... 633 3.2. Characterization of nanoformulations ............................................. 633 3.3. Process development at lab and commercial scales ..................................... 634 3.3.1. Feasibility of nanosuspension ............................................ 634 3.3.2. Nanosuspension for toxicology study ........................................ 635 3.3.3. Nanoformulation for clinical applications ...................................... 636 4. Biopharmaceutical evaluations of nanoformulations ......................................... 637 4.1. Computational approach — predicting performance of nanoformulations .......................... 637 4.2. Nanoformulations for toxicology studies ........................................... 637 4.3. Nanoformulations for preclinical and clinical applications .................................. 639 4.3.1. In vitro studies ................................................... 639 4.3.2. Preclinical studies .................................................. 639 4.3.3. Clinical applications ................................................. 641 5. Nanosuspensions for non-oral applications ............................................. 641 Advanced Drug Delivery Reviews 59 (2007) 631 – 644 www.elsevier.com/locate/addr ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on “Drug solubility: How to measure it, how to improve it”. ⁎ Corresponding author. Merck & Co., Inc., WP75B-310, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486-0004, USA. Tel.: +1 215 652 6911; fax: +1 215 993 2265. E-mail addresses: filippos_kesisoglou@merck.com (F. Kesisoglou), santipharp_panmai@merck.com (S. Panmai), yunhui_wu@merck.com (Y. Wu). 0169-409X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2007.05.003