J. MICROENCAPSULATION, 1997, VOL. 14, NO. zyxwvu 5, 567-576 zyxw Chitosan microcapsules as controlled release systems for insulin K. AIEDEH, E. GIANASI, I. ORIENT1 and V. ZECCHI* Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Bologna, Via San Donato 19, zyxwvu 1-40127 Bologna, Italy zyxwv (Received 18 April 1996; accepted 20 August 1996) This study analyses the use of chitosan for the production of surface crosslinked microparticulate systems containing insulin. The microcapsules were prepared by an innovative technique based on interfacial crosslinkage of different amounts of chitosan solubilized in the inner phase of a water/oil emulsion by means of ascorbyl palmitate. The correlation between the main formulation parameters and the functional properties of the microcapsules were analysed. Insulin is incorporated with high efficiency. The peptide release is constant for appreciable periods of time. The content of chitosan modulates the main physico-chemical properties of the matrix. Keywords: Chitosan, insulin, microcapsules, interfacial crosslinkage, release kinetics. Introduction The controlled release of peptidic drugs from microparticulate systems is at present mainly based on lipophilic biodegradable polymers allowing microparticle preparation by extraction or evaporation of the organic solvent solubilizing the polymer in an oillwater dispersion (Maulding 1987, Hora et al. 1989, Wyse et al. 1989, DamgC et al. 1990, Bodmeier et al. 1992). These techniques are less disruptive for the peptide drugs utilized in microparticle preparation, as the organic solvent does not appreciably solubilize peptidic drugs which are namely hydrophilic, so avoiding undesired alterations or reactions of the peptidic mole- cule. However, a drawback of these techniques is the production of poorly loaded microparticles due to drug solubilization in the external aqueous phase of the preparative dispersion before solidification of the polymeric matrix following solvent extraction or evaporation (Bodmeier and McGinity 1987, 1988). Drug release is hindered in the polymer systems by the slight solubility and diffusivity of peptidic drugs in the lipophilic polymeric matrix. As bulk erosion takes place, the changes in the physico-chemical characteristics of the matrix affecting drug solubility and diffusivity over time make the release rate neither linear nor predictable (Wang et al. 1991, Shaha et al. 1992, Sah et al. 1994). The design of microparticulate systems based on hydrophilic surface cross- linked polymers could therefore provide a means to overcome the problems in the preparation and release of the microparticulate systems based on lipophilic polymers containing peptidic drugs. *To whom all correspondence should be addressed. 0265-2048/97 $12.00 zyxwvut 0 1997 Taylor zyxwvu & Francis Ltd. Journal of Microencapsulation Downloaded from informahealthcare.com by D S Diffusioni Scientifiche - Unical on 05/07/14 For personal use only.