A comparative study of approaches used to improve solubility of roxithromycin Shailesh V. Biradar, Arpana R. Patil, Guditi V. Sudarsan, Varsha B. Pokharkar ⁎ Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra State, India Received 16 November 2005; received in revised form 25 July 2006; accepted 25 July 2006 Available online 11 September 2006 Abstract Roxithromycin (ROX), a class IV drug has 50% absolute oral bioavailability due to poor aqueous solubility. The present study deals with exploring the effect of homogenization, homogenization followed by freeze drying and homogenization followed by spray drying in the presence of solubilizers on drug solubility and dissolution rate. Homogenization and subsequent freeze drying resulted in 3–4 fold increase in saturation solubility and 18 times faster dissolution as compared to the pure drug. In this study, a more preferred aqueous system was developed for enhancement of the saturation solubility and dissolution rate and compared with the non-aqueous system. Interestingly the aqueous system was found equally effective and comparatively more stable. Enhancement of the saturation solubility and dissolution rate was a result of significant particle size reduction, improved hydrophilicity and complete or partial transformation to amorphous form as evidenced by DSC and XRPD studies. The study focused on utilization of solubilizer to synergistically enhance the efficiency of the processing techniques. The effect of processing and formulation variables on the saturation solubility, in vitro dissolution, drug crystallinity, physical interaction, antimicrobial activity and stability was also monitored. © 2006 Elsevier B.V. All rights reserved. Keywords: Freeze drying; Spray drying; Roxithromycin; Ultra turrax; Homogenization 1. Introduction It is estimated that 40% or more of active substances being identified through combinatorial screening programs are poorly soluble in water, which is a critical determinant of oral bioavail- ability [1,2]. Solubility of many newly developed high-potential drugs is an obstacle in formulation development, especially when they show poor solubility simultaneously in aqueous and organic media, which leads to a poor and/or varying bioavail- ability after oral administration. Biopharmaceutical Classifica- tion System for drugs highlights dissolution as the rate-limiting step for oral absorption of class II and IV drugs [3]. Conven- tional dosage forms of these drugs, therefore, often have erratic and variable performance in preclinical and clinical evaluation leading to sub-optimal therapeutic concentration. Generally, it is more expeditious and cost effective to chemically re-design the molecule, than to move a blemished molecule through the development process [4]. In such cases, there is a need for development of an effective formulation, which is capable of overcoming this limitation and delivers the drug at optimal concentration for the desired therapeutic effect. Particle size and crystallinity are most important physico- chemical properties to affect physico-chemical stability, solu- bility and absorption of drug substances as well as compression properties in the manufacturing process. The amorphous state, the complement of the crystalline state, is characterized by disordered molecular or atomic arrangement, which is produced by the grinding of a single component, grinding it with some excipients, mixing it with porous substances, freeze drying, compression, desorption of water of crystallization or spray drying [5,6]. The dissolution behavior and bioavailability of water insoluble drugs could be improved by producing them in more soluble amorphous form [7,8]. The preparation, charac- terization and stabilization of amorphous pharmaceutical solids have been well discussed in several reviews [9–11]. Several approaches have been attempted to improve the solubility and dissolution characteristics of poorly water-soluble Powder Technology 169 (2006) 22 – 32 www.elsevier.com/locate/powtec ⁎ Corresponding author. Tel.: +91 20 25437237; fax: +91 20 25439383. E-mail address: varshapokharkar@yahoo.co.in (V.B. Pokharkar). 0032-5910/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.powtec.2006.07.016