International Journal of Pharmaceutics 288 (2005) 35–49 Hyaluronan-based microspheres as tools for drug delivery: a comparative study Elisabetta Esposito ∗ , Enea Menegatti, Rita Cortesi Department of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 19, I-44100 Ferrara, Italy Received 2 March 2004; received in revised form 18 August 2004; accepted 5 September 2004 Available online 5 November 2004 Abstract The present paper describes the production of biodegradable microparticles using different hyaluronan polymers, such as native hyaluronan, the esterified derivative of hyaluronan Hyaff 11p50 (where 50% of the carboxy groups of hyaluronic acid are esterified with benzyl alcohol) and the autocross-linked polymer (ACP) internally esterified derivative of hyaluronan, by solvent evaporation and spray-drying methods. As model drugs cromolyn sodium salt, metronidazole and prednisolone hemisuccinate sodium salt were employed. The influence of polymer and preparation procedure has been evaluated on microparticle characteristics (i.e. morphology and encapsulation yield) and on the drug release profiles. The use of solvent evaporation method, a polymeric matrix constituted of Hyaff 11p50 3% (w/v), a dispersing phase constituted of 80 g of mineral oil (w/o ratio: 0.1), Span 85 0.1% (w/w) as stabilizer, and a stirring speed of 700 rpm resulted in the production of microspheres characterized by spherical shape, absence of aggregates, a mean diameter of 6.4 m and a recovery of 90% (w/w). The production of drug containing microspheres led to an increase of mean diameter of microspheres and to high encapsulation yields. Moreover in vitro models have demonstrated that in all cases drugs were released from Hyaff 11p50 microspheres in a controlled fashion. Finally mathematical analysis of the drug release modalities has evidenced that drug release from Hyaff 11p50 microspheres is more consistent with kinetics of the diffusion rather than of the dissolution type. © 2004 Elsevier B.V. All rights reserved. Keywords: Hyaff 11p50; Microspheres; Solvent evaporation; Spray-drying 1. Introduction Hyaluronan (HA) is an abundant non-sulfated gly- cosaminoglycan component of synovial fluid and ex- ∗ Corresponding author. Tel.: +39 0532 291259; fax: +39 0532 291296. E-mail address: ese@unife.it (E. Esposito). tracellular matrices. It can be considered as an attractive building block for new biocompatible and biodegrad- able polymers, having applications in drug delivery, tissue engineering, and viscosupplementation (Pouyani et al., 1994; Vercruysse and Prestwich, 1998). Never- theless, the poor biomechanical properties of hyaluro- nan prevent the fabrication of new biomaterials. At this regard a variety of chemical modifications of native 0378-5173/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2004.09.001