International Journal of Pharmaceutics 285 (2004) 87–96 Preparation and characterisation of poly(vinyl alcohol)/ cyclodextrin microspheres as matrix for inclusion and separation of drugs Marieta Constantin a,b , Gheorghe Fundueanu a,b , Fabrizio Bortolotti a , Rita Cortesi a,∗ , Paolo Ascenzi c , Enea Menegatti a a Department of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 19 44100 Ferrara, Italy b Department of Bioactive and Biocompatible Polymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iassy, Romania c Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University “Roma Tre”, I-00146 Rome, Italy Received 1 April 2004; received in revised form 13 July 2004; accepted 22 July 2004 Available online 15 September 2004 Abstract Poly(vinyl alcohol) (PVA) microspheres containing cyclodextrin (CD) were obtained by chemical cross-linking with glu- taraldehyde of an acidified mixture solution of PVA and -, - or -CD. The amount of linked CD in microspheres, estimated by tetrazolium blue method, decreases in the order -> -> -CD. The dimensions of PVA/-CD microspheres are much higher than those of PVA/- and -CD. The cross-linking density of microspheres was estimated by the amount of iodine retained by the polymer matrix. The pore size as well as the porous volume of PVA/CD microspheres decrease significantly on increasing the amount of glutaraldehyde, but are enough large to permit the access of drugs to the CD cavity. In order to test the PVA/CD microsphere inclusion ability, the microspheres were packed in a glass column and the liquid chromatographic behaviour by isocratic elution of different drugs or typical organic compounds, taken as model drugs, was investigated. © 2004 Elsevier B.V. All rights reserved. Keywords: Poly(vinyl alcohol)/Cyclodextrins; Microspheres; Inclusion complexes; Liquid chromatography Abbreviations: BA, benzoic acid; CAB, cellulose acetate bu- tyrate; CR, congo red; CD, cyclodextrin; EP, ethyl-paraben; GA, glutaraldehide; HPLC, high performance liquid chromatography; In, indol; ISEC, inverse size exclusion chromatography; MP, methyl- paraben; PE, propyl-paraben; PVA, poly(vinyl alcohol); S.D., stan- dard deviation; SEM, scanning electron microscopy ∗ Corresponding author. Tel.: +39 0532 291259; fax: +39 0532 291296. E-mail address: crt@unife.it (R. Cortesi). 1. Introduction Poly(vinyl alcohol) (PVA) is a hydrophilic polymer that is frequently used in biomedical applications such as implants (Juang et al., 1996), soft contact lenses (Hyon et al., 1994), artificial organs (Chen et al., 1994) and protein immobilization (Kobayashi and Ykada, 1991; Uhlich et al., 1999). The large applicability of PVA depends on its low price, easy 0378-5173/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2004.07.025