Research paper Tableting and stability evaluation of enteric-coated omeprazole pellets Murat Tu ¨rkog ˘lu * , Hakan Varol, Mine C ¸ elikok Pharmaceutical Technology Department, Faculty of Pharmacy, Marmara University, Istanbul, Turkey Received 7 March 2003; accepted in revised form 24 October 2003 Abstract In this study, fluidized-bed manufactured enteric-coated omeprazole pellets were compressed into tablets. The stability of the pellets and those of compressed tablets were evaluated for remaining omeprazole and for degradation products under an accelerated stability protocol. The data were analyzed using the artificial neural network (ANN) and analysis of variance (ANOVA). It was found that enteric-coated omeprazole pellets could be compressed into quickly disintegrating tablets using microcrystalline cellulose granules as the pressure absorbing matrix. The ANN, using the multilayer perceptron model, predicted that there was a positive correlation between tablet crushing strength and microcrystalline cellulose concentration. Microcrystalline cellulose matrix showed a strong plastic deformation and all the pellets inside the tablet maintained their integrity with no significant change in their surface properties. Omeprazole degradation in acid medium was mainly dependent on microcrystalline cellulose concentration. A 90-day accelerated stability test in brown glass bottles with a desiccant showed that all prototype formulations would result in an acceptable stability profile for both remaining omeprazole, and also for the increase of impurity concentrations. q 2003 Elsevier B.V. All rights reserved. Keywords: Pellets; Artificial neural networks; Pellet compression; Omeprazole; Accelerated stability 1. Introduction Tableting of multiparticulate systems such as pellets and microspheres is an attractive approach to prepare a single unit dosage form that will readily disintegrate into its essential components when exposed to gastro-intestinal fluid. That type of dosage form will maintain the advantages of pellets despite being a tablet. There are two points of interest when compressing a coated particle. The first one is the effect of excipients, and the other is the composition and the amount of coating on the particle. In this study, we only investigated the effect of excipients on coated particles. The polymer type and the polymer/plasticizer ratio were kept constant for the optimized enteric-coated product. Maganti and C ¸ elik reported that increasing the amount of polymer on the coated particles reduced their yield strengths and resulted in compacts with lower tensile strength and higher elastic recovery, pellets coated with increasing amounts of coating exhibited relatively more punch velocity depen- dence [1]. Schmidt et al. found that the most important factors were the coating polymer and the amount of coating when enteric-coating integrity was tested for bisacody pellets in acid medium after compression [2]. Another report by Schmidt et al. focused on the effect of excipients on enteric-coated pellets and for approximately 1 mm pellets, the larger size Avicel granules caused more deformation of pellets but less damage to the coating in comparison to Avicel PH 101 powder and it was also concluded that damage to the coating mainly occurred on the tablet surface during compression [3]. Beckert and Lieneweg reported that it was possible to compress enteric- coated pellets into tablets without significant damage using Eudragit L30 D-55 at 35% level and propylene glycol at 20% level as preferred plasticizers [4]. Lefranc et al. also reported similar findings for enteric-coated 5-ASA pellets [5]. Omeprazole is a member of acid-labile H þ K þ - ATPase inhibitors also known as gastric proton pump inhibitors. Omeprazole is sensitive to heat, humidity, light, and organic solvents. Discoloration ranging from light beige to deep purple will occur immediately when omeprazole is exposed to unfavorable conditions. Stability of omeprazole for different pH values in solution was reported by Bailey 0939-6411/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2003.10.008 European Journal of Pharmaceutics and Biopharmaceutics 57 (2004) 279–286 www.elsevier.com/locate/ejpb * Corresponding author. Address: Pharmaceutical Technology Department, Faculty of Pharmacy, Marmara University, 34668 Haydarpas ¸a, Istanbul, Turkey. Tel.: þ 90-216-418-5029; fax: þ 90-216- 345-2952. E-mail address: turkoglu@marmara.edu.tr (M. Tu ¨rkog ˘lu).