Preparation of gastroresistant mesalazine lipidic microcapsules

INTRODUCTION AND OBJECTIVES Mesalazine or 5-aminosalicylic (5-ASA), a typical antiinflatmmatory drug, is customarily used to maintain remission in inflammatory bowel disease (Carter, 2004). Mesalazine acts topically on the colonic mucosa: current 5-ASA delivery systems have been developed to avoid absorption of mesalazine in the small intestine, thereby delivering maximal amounts of the drug to colonic mucosa (Van den Mooter 2006). The aim of this work was to develop and characterize gastro-resistant multiparticulate system for mesalazine colon delivery in paediatric administration. MATERIAL AND METHODS Mesalazine was kindly supplied by Doppel (Cortemaggiore, Italy) and stearic acid was purchased by ACEF (Fiorenzuola, Italy). Carnauba wax (Produits Roche S.A. France) and Eudragit (Rhom Pharma, Germany) were also used. All other chemicals were of analytical grade. The 5-ASA microcapsules were manufactured in two steps through the spray-congealing technique. In the first step the mesalazine was disperded in a solution of Eudragit L in isopropyl alcohol prepared under stirring at the tempetature of 70°C. The carnauba wax was added to the dispersion and the temperature was raised up until 95°C to evaporate the isopropyl alcohol and io melt the lipid. The melted mass was sprayed through the WPN nozzle at 3.0 bar. In the second step the microcapsules were obtained by disperding the 5-ASA cores in a low melting point lipid as stearic acid at the temperature around 70°C. At this temperature the microsphere did not melt and remained well dispersed in the liquid mass. The dispersion was sprayed with the WPN nozzle at 1.2 bar and the microcapsules were obtained. The drug loading was determined by adding the samples to a simulated intestinal fluid (SIF) at pH 7.4 and heating up to 70°C or to 850C to melt the lipophilic carrier as stearic acid or carnauba wax, respectively. The process was carried out under magnetic stirring for 5 hours to extract completely the 5-ASA. The solution was filtered with microcellulose filter and then assayed by UV at 330 nm. The analysis was peformed in triplicate. The lipid microcapsules were examined both under an optical stereomicroscope (Citoval 2. Jena, Germany) connected to a video camera (JVC, Tokyo, Japan) and Scanning Electron Microscopy (SEM, JSM 6400, Jeol Ltd. Tokyo, Japan). Physical changes in microcapsules during heating were monitored by Hot Stage Microscopy (HSM). A hot plate (FP 52 Mettler, Grefensee, Switzerland) connected to a temperature controller (FP 5 Mettler) was used ...........