Research paper Preparation of amorphous cefuroxime axetil nanoparticles by sonoprecipitation for enhancement of bioavailability Ravindra S. Dhumal a , Shailesh V. Biradar a , Shigeo Yamamura b , Anant R. Paradkar a,c, * , Peter York c a Department of Pharmaceutics, Poona College of Pharmacy and Research Centre, Bharati Vidyapeeth University, Maharashtra, India b Department of Pharmaceutical Sciences, Josai International University, Chiba, Japan c Institute of Pharmaceutical Innovations, University of Bradford, West Yorkshire, UK Received 19 November 2007; accepted in revised form 4 April 2008 Available online 11 April 2008 Abstract The aim of the present work was to prepare amorphous discreet nanoparticles by sonoprecipitation method for enhancing oral bio- availability of cefuroxime axetil (CA), a poorly water-soluble drug. CA nanoparticles (SONO-CA) were prepared by sonoprecipitation and compared with particles obtained by precipitation without sonication (PPT-CA) and amorphous CA obtained by spray drying. Spray drying present broad particle size distribution (PSD) with mean particle size of 10 lm and low percent yield, whereas, precipitation without sonication resulted in large amorphous aggregates with broad PSD. During sonoprecipitation, particle size and yield improve with an increase in the amplitude of sonication and lowering the operation temperature due to instantaneous supersaturation and nucle- ation. The overall symmetry and purity of CA molecule was maintained as confirmed by FTIR and HPLC, respectively. All the three methods resulted in the formation of amorphous CA with only sonoprecipitation resulting in uniform sized nanoparticles. Sonoprecip- itated CA nanoparticles showed enhanced dissolution rate and oral bioavailability in Wistar rat due to an increased solubility attributed to combination of effects like amorphization and nanonization with increased surface area and reduced diffusion pathway. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Cefuroxime axetil; Sonoprecipitation; Amorphous; Nanoparticles; Bioavailability 1. Introduction CA is 1-acetoxyethyl ester of a b-lactamase-stable ceph- alosporin, cefuroxime (C) with a broad spectrum of activity against Gram-positive and Gram-negative microorganisms [1]. After oral administration CA is absorbed and rapidly hydrolysed by esterases in the intestinal mucosa and portal blood to produce C. The 1-acetoxyethylester group in posi- tion 4 of CA ensures lipophilicity and promotes the intesti- nal absorption of C but at the same time compromise on solubility and hence, the prodrug shows poor and variable oral bioavailability [2]. CA exists in crystalline as well as amorphous form, of these latter exhibits higher bioavail- ability owing to improved solubility. But, its bioavailability is variable and limited to 30% in fasted and 50% in fed states [3,4]. The most successful attempt for achieving amorphous CA from commercial point of view was through spray drying [3,4]. Nanoparticles are known to improve dissolution rate and bioavailability of poorly water-soluble drugs [5–9] owing to increased surface area available for dissolution as described by the Noyes–Whitney equation [10]. Nano- particles are generally obtained by ‘top–down’ process which relies on mechanical attrition [9]. However, it is energy-intensive, time-consuming and show some disad- vantages in practice such as the introduction of impurities, inadequate control of particle size and electrostatic effects. In the last decade, ‘bottom–up’ techniques like supercritical 0939-6411/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2008.04.001 * Corresponding author. Department of Pharmaceutics, Bharati Vidy- apeeth University, Poona College of Pharmacy and Research Centre, Erandawane, Pune 411038, Maharashtra, India. Tel.: +91 20 2543 7237; fax: +91 20 2543 9383. E-mail address: arparadkar@rediffmail.com (A.R. Paradkar). www.elsevier.com/locate/ejpb Available online at www.sciencedirect.com European Journal of Pharmaceutics and Biopharmaceutics 70 (2008) 109–115